When should temporal-lobe epilepsy be treated surgically?

PubMed

Spencer, Susan S

2002-10-01

Our current knowledge of mesial-temporal-lobe epilepsy (MTLE) is extensive, yet still insufficient to draw final conclusions on the optimal approach to its therapy. MTLE has been well characterised and can usually be identified with noninvasive studies including scalp electroencephalography (EEG) and video monitoring with ictal recording, magnetic resonance imaging, single-photon-emission computed tomography, positron emission tomography, neuropsychological assessment, and historical and clinical data. Sometimes, invasive EEG is needed to confirm mesial-temporal-lobe seizure onset, which, combined with the underlying pathological abnormality (the substrate) of mesial temporal sclerosis (hippocampal neuronal loss and gliosis), defines MTLE. This disorder is the most common refractory partial epilepsy, and also the one most often treated surgically, because medical treatment fails in 75% of cases, and surgical treatment succeeds in a similar percentage. Despite the recent publication of the first randomised trial of surgical treatment for MTLE, questions remain about the neurological consequences of both medical and surgical treatment, the ultimate gains in quality of life parameters, and the precise predictors of success. Long-term follow-up and analyses of multiple factors in large groups of contemporary patient populations will be necessary to fully answer the question, "is temporal lobe epilepsy a surgical disease?" Right now it should be considered one in most cases.

Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study.

PubMed

Zhu, Xi; He, Zhongqiong; Luo, Cheng; Qiu, Xiangmiao; He, Shixu; Peng, Anjiao; Zhang, Lin; Chen, Lei

2018-03-15

To investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). Eighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. The PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. The PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Right fronto-limbic atrophy is associated with reduced empathy in refractory unilateral mesial temporal lobe epilepsy.

PubMed

Toller, Gianina; Adhimoolam, Babu; Rankin, Katherine P; Huppertz, Hans-Jürgen; Kurthen, Martin; Jokeit, Hennric

2015-11-01

Refractory mesial temporal lobe epilepsy (MTLE) is the most frequent focal epilepsy and is often accompanied by deficits in social cognition including emotion recognition, theory of mind, and empathy. Consistent with the neuronal networks that are crucial for normal social-cognitive processing, these impairments have been associated with functional changes in fronto-temporal regions. However, although atrophy in unilateral MTLE also affects regions of the temporal and frontal lobes that underlie social cognition, little is known about the structural correlates of social-cognitive deficits in refractory MTLE. In the present study, a psychometrically validated empathy questionnaire was combined with whole-brain voxel-based morphometry (VBM) to investigate the relationship between self-reported affective and cognitive empathy and gray matter volume in 55 subjects (13 patients with right MTLE, 9 patients with left MTLE, and 33 healthy controls). Consistent with the brain regions underlying social cognition, our results show that lower affective and cognitive empathy was associated with smaller volume in predominantly right fronto-limbic regions, including the right hippocampus, parahippocampal gyrus, thalamus, fusiform gyrus, inferior temporal gyrus, dorsomedial and dorsolateral prefrontal cortices, and in the bilateral midbrain. The only region that was associated with both affective and cognitive empathy was the right mesial temporal lobe. These findings indicate that patients with right MTLE are at increased risk for reduced empathy towards others' internal states and they shed new light on the structural correlates of impaired social cognition frequently accompanying refractory MTLE. In line with previous evidence from patients with neurodegenerative disease and stroke, the present study suggests that empathy depends upon the integrity of right fronto-limbic and brainstem regions and highlights the importance of the right mesial temporal lobe and midbrain structures for human empathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lesional Temporal Lobe Epilepsy: Beware the Deceitful "Panic Attack".

PubMed

Kulason, Kay O; Schneider, Julia R; Rahme, Ralph; Pramanik, Bidyut; Chong, Derek; Boockvar, John A

2018-03-01

Ganglioglioma is a rare, benign, intraaxial glioneuronal tumor but a relatively common cause of pharmacoresistant temporal lobe epilepsy (TLE). Given its often nonspecific neuropsychiatric manifestations and frequently negative electroencephalographic workup, TLE can be easily misdiagnosed as a psychiatric disorder, particularly panic attacks. We present a case of a 17-year-old boy who was found to have lesional TLE secondary to a left temporal ganglioglioma, 5 years after having been misdiagnosed with panic disorder and having undergone ineffective and unnecessary psychotherapy. He was successfully cured by surgery. Although a few similar cases of TLE masquerading as a panic disorder have been previously reported in the literature, this is the youngest and only pediatric patient described to date. This report underscores the challenges in making an accurate clinical diagnosis of TLE and the importance of timely brain imaging whenever an atypical or medically refractory panic disorder is encountered. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy.

PubMed

Gales, Jordan M; Prayson, Richard A

2017-10-01

Emerging evidence suggests chronic inflammation may play a role in hippocampal sclerosis-associated temporal lobe epilepsy. We sought to systematically evaluate for its presence in a group of 315 patients who underwent surgery for medically-refractory epilepsy and who had hippocampal sclerosis. Upon histologic review of hematoxylin and eosin stained tissue sections, 95 (41%) cases demonstrated the presence of lymphocytes within the perivascular region and diffusely within the brain parenchyma. Those cases with chronic inflammation evident on hematoxylin and eosin staining were significantly more likely to experience a post-operative seizure recurrence than those without it (p=0.03). In 9 cases of hippocampi with chronic inflammation observed on hematoxylin and eosin stained sections, there was a mixture of both T (CD3+) and B (CD20+) lymphocytes located around blood vessels and interspersed within the brain parenchyma and a predominance of CD4 positive T cells versus CD8 positive cells. Ten hippocampi, apparently devoid of chronic inflammation upon inspection with hematoxylin and eosin stained sections, were stained with the lymphocyte common antigen CD45. In all 10 cases, scattered lymphoid cells were observed in the brain parenchyma, suggesting some level of chronic inflammation may be present in more cases than casual inspection might suggest. This study was the first to evaluate the incidence of chronic inflammation within a large temporal lobe epilepsy population. The study findings suggest chronic inflammation may be a more common component of hippocampal sclerosis -associated temporal lobe epilepsy than previously believed. Copyright © 2017 Elsevier Inc. All rights reserved.

[Pathological neocortical findings in patients with medication-resistant medial temporal lobe epilepsy submitted to surgery].

PubMed

Estupiñán-Díaz, B; Morales-Chacón, L M; Lorigados-Pedre, L; García-Maeso, I; Bender-del Busto, J E; Trápaga-Quincoses, O; Hidalgo-Portal, L; García-Navarro, M E; Sánchez-Coroneaux, A; Orozco-Suárez, S

The dual pathology consisting of hippocampal sclerosis plus focal cortical dysplasia (FCD) is often reported in patients with medication-resistant medial temporal lobe epilepsy (MTLE). To determine the histopathological changes that take place in the neocortex of patients with medication-resistant MTLE submitted to surgery and to evaluate the relation between the histopathological changes, pathological background and the clinical course of patients who had received surgical treatment. Tissue obtained by en bloc resection from the neocortex of 18 patients with MTLE refractory to medical treatment was processed histologically and a tailored temporal lobectomy was performed with electrocorticography. Dual pathology was diagnosed in 13 patients (72.2%). Imaging studies confirmed the existence of mesial sclerosis of the temporal in 100% of cases and there was no evidence of neocortical lesions. Histologically, 46.15% and 38.46% of the patients were diagnosed as belonging to FCD type 1a and FCD type 1b, respectively. Only one patient presented FCD type 2a. A statistically significant relation was found between the presence of dual pathology and the existence of an early precipitating injury (p = 0.04). One year after surgery, 72.7% (8/11) patients with dual pathology were classified as belonging to Engel class I. In patients with MTLE there are microscopic FCD-type alterations in the neocortex. There is an association between these alterations and the existence of an initial precipitating injury. Complete resection of the epileptogenic area, which is guaranteed by the lobectomy tailored by electrocorticography, allows patients to enjoy a favourable post-surgical progression one year after surgery.

Pediatric Temporal Lobe Epilepsy Surgery in Bonn and Review of the Literature.

PubMed

Ormond, D Ryan; Clusmann, Hans; Sassen, Robert; Hoppe, Christian; Helmstaedter, Christoph; Schramm, Johannes; Grote, Alexander

2018-04-13

Epilepsy surgery is well established as safe and successful for children with temporal lobe epilepsy (TLE). Despite evidence from available data, there remains some reluctance to refer children with medically refractory epilepsy for preoperative evaluation and workup for possible surgery. To present the largest case series of pediatric (TLE) patients thus far, in order to better understand the predictability of preoperative evaluation on seizure outcome, and to better understand longitudinal outcomes in a large pediatric cohort. One hundred eighty-three pediatric patients with TLE who underwent surgical treatment between 1988 and 2012 were retrospectively reviewed. Preoperative seizure history, noninvasive and invasive preoperative evaluation, surgical results, pathological results, long-term seizure outcomes, and complications were evaluated. A review of pediatric TLE in the literature was also undertaken to better understand reported complications and long-term outcomes. Mean follow-up was 42 mo (range 12-152 mo); 155 patients had good seizure outcomes (Engel I/II; 84.8%) and 28 patients had poor seizure outcomes (Engel III/IV; 15.2%); 145 patients were Engel I (78.8%). Only 10 patients did not have worthwhile improvement (Engel class IV; 5.4%). A review of the literature identified 2089 unique cases of pediatric TLE. Satisfactory seizure outcomes occurred in 1629 patients (79%) with unsatisfactory outcomes in 433 patients (21%). Pediatric patients benefit from surgery for medically refractory TLE with an acceptable safety profile regardless of histopathological diagnosis, seizure frequency, or seizure type. Seizure freedom appears to have extensive durability in a significant proportion of surgically treated patients.

Evaluation of Posterior Hippocampal Epileptogenicity During Epilepsy Surgery For Temporal Lobe Cavernoma by the Occipital Approach.

PubMed

Akiyama, Yukinori; Suzuki, Kengo; Ochi, Satoko; Miyamoto, Susumu; Mikuni, Nobuhiro

2015-11-01

Cavernomas frequently are associated with intractable epilepsy. When cavernomas located in the temporal lobe are associated with intractable epilepsy, the hippocampus also may have an epileptic focus. The objective in the present study was to clarify the importance of evaluation of the posterior hippocampal epileptogenicity during epilepsy surgery for posteromedial temporal lobe cavernoma. In this study, we describe 2 rare cases of medically intractable epilepsy in patients with posteromedial temporal lobe cavernomas who underwent surgery via the occipital approach. Using longitudinal insertion of depth electrodes into the hippocampus, we evaluated epileptogenicity in both patients from the cavernoma cavity and its surrounding hemosiderin, as well as from the posterior hippocampus near the cavernoma. We show that the transoccipital approach to the posteromedial temporal lobe is compatible with depth electrode insertion and subdural electrode placement on the temporal lobe, enabling an accurate evaluation of potential epileptogenic zones in the posterior part of the hippocampus. Both patients did not experience any seizures and had no postoperative neurologic deficits, and their cognitive functions were intact. The transoccipital approach enables the optimization of the extent of posterior hippocampectomy while avoiding unnecessary resection for seizure control. We suggest resecting the posterior part of the hippocampus in addition to the cavernoma and surrounding areas in patients with medically refractory epilepsy due to a posteromedial temporal cavernoma. Tailored systematic resection guided by intraoperative electrocorticography and electroencephalography with a depth electrode was important and necessary in the present cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality.

PubMed

Bartolini, Luca; Whitehead, Matthew T; Ho, Cheng-Ying; Sepeta, Leigh N; Oluigbo, Chima O; Havens, Kathryn; Freilich, Emily R; Schreiber, John M; Gaillard, William D

2017-01-01

To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD). We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies. Rates of pathology subtypes differed between TLE and ETLE (χ 2 (3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ 2 (1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ 2 (1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ 2 (6) = 13.07, p = 0.042). Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

PubMed

Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

2016-09-01

Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the contralateral hippocampus after surgery suggests the possibility of an early post-operative imaging marker to predict surgical outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Temporal lobe epilepsy surgery in children versus adults: from etiologies to outcomes

PubMed Central

Lee, Yun-Jin

2013-01-01

Temporal lobe epilepsy (TLE) is the most common type of medically intractable epilepsy in adults and children, and mesial temporal sclerosis is the most common underlying cause of TLE. Unlike in the case of adults, TLE in infants and young children often has etiologies other than mesial temporal sclerosis, such as tumors, cortical dysplasia, trauma, and vascular malformations. Differences in seizure semiology have also been reported. Motor manifestations are prominent in infants and young children, but they become less obvious with increasing age. Further, automatisms tend to become increasingly complex with age. However, in childhood and especially in adolescence, the clinical manifestations are similar to those of the adult population. Selective amygdalohippocampectomy can lead to excellent postoperative seizure outcome in adults, but favorable results have been seen in children as well. Anterior temporal lobectomy may prove to be a more successful surgery than amygdalohippocampectomy in children with intractable TLE. The presence of a focal brain lesion on magnetic resonance imaging is one of the most reliable independent predictors of a good postoperative seizure outcome. Seizure-free status is the most important predictor of improved psychosocial outcome with advanced quality of life and a lower proportion of disability among adults and children. Since the brain is more plastic during infancy and early childhood, recovery is promoted. In contrast, long epilepsy duration is an important risk factor for surgically refractory seizures. Therefore, patients with medically intractable TLE should undergo surgery as early as possible. PMID:23908666

Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1 2

PubMed Central

Szabo, Gergely G.; Armstrong, Caren; Oijala, Mikko; Soltesz, Ivan

2014-01-01

Abstract Cover Figure Krook-Magnuson et al. report a bidirectional functional connectivity between the hippocampus and the cerebellum in a mouse model of temporal lobe epilepsy, and demonstrate that cerebellar directed on-demand optogenetic intervention can stop seizures recorded from the hippocampus. Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited. PMID:25599088

Nonvisual spatial navigation fMRI lateralizes mesial temporal lobe epilepsy in a patient with congenital blindness.

PubMed

Toller, Gianina; Adhimoolam, Babu; Grunwald, Thomas; Huppertz, Hans-Jürgen; König, Kristina; Jokeit, Hennric

2015-01-01

Nonvisual spatial navigation functional magnetic resonance imaging (fMRI) may help clinicians determine memory lateralization in blind individuals with refractory mesial temporal lobe epilepsy (MTLE). We report on an exceptional case of a congenitally blind woman with late-onset left MTLE undergoing presurgical memory fMRI. To activate mesial temporal structures despite the lack of visual memory, the patient was requested to recall familiar routes using nonvisual multisensory and verbal cues. Our findings demonstrate the diagnostic value of a nonvisual fMRI task to lateralize MTLE despite congenital blindness and may therefore contribute to the risk assessment for postsurgical amnesia in rare cases with refractory MTLE and accompanying congenital blindness.

Postictal psychosis and its electrophysiological correlates in invasive EEG: a case report study and literature review.

PubMed

Kuba, Robert; Brázdil, Milan; Rektor, Ivan

2012-04-01

We identified two patients with medically refractory temporal lobe epilepsy, from whom intracranial EEG recordings were obtained at the time of postictal psychosis. Both patients had mesial temporal epilepsy associated with hippocampal sclerosis. In both patients, the postictal psychosis was associated with a continual "epileptiform" EEG pattern that differed from their interictal and ictal EEG findings (rhythmical slow wave and "abortive" spike-slow wave complex activity in the right hippocampus and lateral temporal cortex in case 1 and a periodic pattern of triphasic waves in the contacts recording activity from the left anterior cingulate gyrus). Some cases of postictal psychosis might be caused by the transient impairment of several limbic system structures due to the "continual epileptiform discharge" in some brain regions. Case 2 is the first report of a patient with TLE in whom psychotic symptoms were associated with the epileptiform impairment of the anterior cingulate gyrus. Copyright © 2012 Elsevier Inc. All rights reserved.

Preoperative therapeutic apheresis for severe medically refractory amiodarone-induced thyrotoxicosis: a case report.

PubMed

Yamamoto, Jennifer; Dostmohamed, Hanifa; Schacter, Isanne; Ariano, Robert E; Houston, Donald S; Lewis, Brenda; Knoll, Colleen; Katz, Pamela; Zarychanski, Ryan

2014-06-01

Amiodarone is associated with thyroid dysfunction and life-threatening thyrotoxicosis. In medically refractory cases, or where medical therapy is contraindicated, thyroidectomy may be required. To decrease perioperative thyroid storm and to reduce overall surgical risk, apheresis may be considered preoperatively to restore euthyroidism. We report a 46-year-old female with a history of cardiac arrhythmia and tachycardia-induced cardiomyopathy for which she received amiodarone. Months after discontinuation of amiodarone, the patient presented with wide complex tachycardia and symptoms of thyrotoxicosis. Laboratory testing confirmed severe thyrotoxicosis which was subsequently refractory to medical therapy. Total thyroidectomy was required. Following a total of 10 apheresis treatments, thyroid hormone levels were reduced to near normal levels and the patient's symptoms improved. Thyroidectomy was performed without intraoperative or postoperative complication. In the setting of life-threatening, medically refractory amiodarone-induced thyrotoxicosis, therapeutic apheresis can effectively reduce thyroid hormone levels and restore a state of clinical and biochemical euthyroidism. © 2013 Wiley Periodicals, Inc.

Safety of Laser Interstitial Thermal Therapy in Patients With Pacemakers.

PubMed

Grewal, Sanjeet S; Gorny, Krzysztof R; Favazza, Christopher P; Watson, Robert E; Kaufmann, Timothy J; Van Gompel, Jamie J

2018-02-10

Laser interstitial thermal therapy (LiTT) has increasingly been used as a treatment option for medically refractory epilepsy, tumors, and radiation necrosis. The use of LiTT requires intraoperative magnetic resonance (MR) thermography. This can become an issue in patients with other implanted therapeutic devices such as pacemakers and vagal nerve stimulators due to concerns regarding increases in the specific absorption rate (SAR). This is a technical case report demonstrating a successfully and safely performed LiTT in a 1.5-T magnetic resonance imaging (MRI) in a patient with a pacemaker for mesial temporal sclerosis. An 83-yr-old gentleman who had an implanted cardiac pacemaker presented with medically intractable epilepsy and was confirmed to have mesial temporal sclerosis on imaging. Video electroencephalography demonstrated concordant ipsilateral seizures and semiology. He underwent LiTT for ablation of the mesial temporal lobe. This was performed with the below described protocol with a cardiology nurse monitoring the patient's cardiac condition and a physicist monitoring SAR, and MR imaging quality without any adverse events. This study reports on a protocol of cardiac and MR SAR to safely perform MR-guided LiTT in the setting of traditional pacemakers in patients who are not pacemaker dependent. Copyright © 2018 by the Congress of Neurological Surgeons

Treatment of Refractory and Super-refractory Status Epilepticus.

PubMed

Rai, Samhitha; Drislane, Frank W

2018-06-19

Refractory and super-refractory status epilepticus (SE) are serious illnesses with a high risk of morbidity and even fatality. In the setting of refractory generalized convulsive SE (GCSE), there is ample justification to use continuous infusions of highly sedating medications-usually midazolam, pentobarbital, or propofol. Each of these medications has advantages and disadvantages, and the particulars of their use remain controversial. Continuous EEG monitoring is crucial in guiding the management of these critically ill patients: in diagnosis, in detecting relapse, and in adjusting medications. Forms of SE other than GCSE (and its continuation in a "subtle" or nonconvulsive form) should usually be treated far less aggressively, often with nonsedating anti-seizure drugs (ASDs). Management of "non-classic" NCSE in ICUs is very complicated and controversial, and some cases may require aggressive treatment. One of the largest problems in refractory SE (RSE) treatment is withdrawing coma-inducing drugs, as the prolonged ICU courses they prompt often lead to additional complications. In drug withdrawal after control of convulsive SE, nonsedating ASDs can assist; medical management is crucial; and some brief seizures may have to be tolerated. For the most refractory of cases, immunotherapy, ketamine, ketogenic diet, and focal surgery are among several newer or less standard treatments that can be considered. The morbidity and mortality of RSE is substantial, but many patients survive and even return to normal function, so RSE should be treated promptly and as aggressively as the individual patient and type of SE indicate.

Epilepsy surgery in a liver-transplanted girl with temporal lobe epilepsy and hippocampal sclerosis following PRES with status epilepticus.

PubMed

Dilena, Robertino; Nebbia, Gabriella; Fiorica, Lorenzo; Farallo, Marcello; Degrassi, Irene; Gozzo, Francesca; Pelliccia, Veronica; Barbieri, Sergio; Cossu, Massimo; Tassi, Laura

2016-07-01

Posterior reversible encephalopathy syndrome (PRES) with status epilepticus may occur after liver transplant. This may rarely lead to refractory epilepsy and hippocampal sclerosis (HS). We report the first case of epilepsy surgery in a liver-transplanted patient with refractory temporal lobe epilepsy. A 3-year-old girl underwent liver transplant for congenital biliary atresia. Four days after transplant she manifested PRES with status epilepticus, but she recovered within a couple of weeks. At the age of 5 years she started presenting complex partial seizures, that became refractory to antiepileptic drugs (AED), worsening psychosocial performances. The pre-surgical work-up identified a left HS and temporal pole alterations. A left antero-mesial temporal lobectomy was performed, leading to epilepsy remission and allowing AED withdrawal. Drug-resistant temporal lobe epilepsy and HS may occur as sequelae of PRES with status epilepticus related to liver transplant and cyclosporine use. In this setting early epilepsy surgery may reduce the time of chronic exposure to AED and severe illness due to repeated seizures. This option might have additional advantages in the subgroup of epileptic patients with liver transplant, preserving the liver from the potential damage due to multiple AED trials and their interaction with commonly used immunosuppressant drugs. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Bilateral perisylvian ulegyria: an under-recognized, surgically remediable epileptic syndrome.

PubMed

Schilling, Lucas P; Kieling, Renata R; Pascoal, Tharick A; Kim, Hyoung-Ihl; Lee, Min Cheol; Kim, Yun Hee; Paglioli, Eliseu; Neto, Pedro R; Costa, Jaderson C; Palmini, Andre

2013-08-01

Interest in the association of epilepsy and pseudobulbar palsy was rekindled since the identification through magnetic resonance imaging (MRI) of bilateral perisylvian polymicrogyria (PMG). Seizures are often intractable, but resective epilepsy surgery has not been recommended. However, a similar clinical picture can be encountered in patients with bilateral perisylvian destructive lesions, which fit the description of ulegyria (ULG). We report a series of patients with epilepsy and pseudobulbar palsy due to bilateral perisylvian ULG (BP-ULG), show that hippocampal sclerosis (HS) is often associated and highlight the fact that in this entity, unlike in malformative bilateral perisylvian PMG, seizures may be surgically treated. The motor, cognitive, epileptologic, and imaging features of 12 patients with perisylvian ULG followed at three institutions are described. For patients with refractory seizures, we detail extracranial and intracranial electrographic recordings, surgical strategies, histopathologic analyses of the resected tissue, and outcome of surgical treatment. Descriptive statistics were used for quantitative and categorical variables. Student's t-test was used to compare means, and a p < 0.05 was considered significant. Pseudobulbar palsy and mental retardation were present in all patients with symmetrical BP-ULG. Five had refractory seizures. There was no relationship between the severity of the pseudobulbar palsy or of the mental retardation and the degree of seizure control with medication. The five patients in whom seizures were refractory to medication had significantly earlier age of onset and longer duration of epilepsy (p < 0.05). Dual pathology with associated unilateral HS was present in four. One patient with dual pathology had a temporolimbic electroclinical picture and had an anterior temporal lobectomy (ATL) based upon noninvasive evaluation. The other four had ictal semiology suggesting involvement of both temporolimbic and perisylvian cortex. Intracranial electroencephalography (EEG) showed concomitant seizure onset in the anterior temporal region and in the ipsilateral ULG in three of the four with dual pathology and in the ulegyric cortex in the one without HS. Resection guided by a combination of semiology, MRI, and extra and intracranial EEG led to complete seizure control in two and almost complete seizure control (Engel class II) in two other patients. The only surgical failure was an isolated ATL in a patient with dual pathology, and concomitant seizure onset in both lesions according to semiology and intracranial EEG. Our findings suggest that BP-ULG mimics the clinical features of bilateral perisylvian PMG. In patients with refractory seizures, recognition of this entity should lead to consideration of resective surgery despite the bilateral ULG. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

The Structural Plasticity of White Matter Networks Following Anterior Temporal Lobe Resection

ERIC Educational Resources Information Center

Yogarajah, Mahinda; Focke, Niels K.; Bonelli, Silvia B.; Thompson, Pamela; Vollmar, Christian; McEvoy, Andrew W.; Alexander, Daniel C.; Symms, Mark R.; Koepp, Matthias J.; Duncan, John S.

2010-01-01

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy…

Creative innovation with temporal lobe epilepsy and lobectomy.

PubMed

Ghacibeh, Georges A; Heilman, Kenneth M

2013-01-15

Some patients with left temporal degeneration develop visual artistic abilities. These new artistic abilities may be due to disinhibition of the visuo-spatially dominant right hemisphere. Many famous artists have had epilepsy and it is possible that some may have had left temporal seizures (LTS) and this left temporal dysfunction disinhibited their right hemisphere. Alternatively, unilateral epilepsy may alter intrahemispheric connectivity and right anterior temporal lobe seizures (RTS) may have increased these artists' right hemisphere mediated visual artistic creativity. To test the disinhibition versus enhanced connectivity hypotheses we studied 9 participants with RTS and 9 with left anterior temporal seizures (LTS) who underwent unilateral lobectomy for the treatment of medically refractory epilepsy. Creativity was tested using the Torrance Test of Creative Thinking (TTCT). There were no between group differences in either the verbal or figural scores of the TTCT, suggesting that unilateral anterior temporal ablation did not enhance visual artistic ability; however, for the RTS participants' figural creativity scores were significantly higher than verbal scores. Whereas these results fail to support the left temporal lobe disinhibition postulate of enhanced figural creativity, the finding that the patients with RTS had better figural than verbal creativity suggests that their recurrent right hemispheric seizures lead to changes in their right hemispheric networks that facilitated visual creativity. To obtain converging evidence, studies on RTS participants who have not undergone lobectomy will need to be performed. Published by Elsevier B.V.

Extracorporeal Membrane Oxygenation in Drug Overdose: A Clinical Case Series

PubMed Central

Vignesh, C.; Kumar, Madhan; Venkataraman, Ramesh; Rajagopal, Senthilkumar; Ramakrishnan, Nagarajan; Abraham, Babu K.

2018-01-01

Overdose of cardiovascular medications such as beta blockers and calcium channel blockers cause impaired cardiac contractility, vasoplegia, and/or rhythm disturbances. In addition to conventional management of limiting absorption, increasing elimination and hemodynamic support intravenous (IV) calcium infusion, hyperinsulinemia-euglycemia therapy, glucagon infusion, and IV lipid emulsion have been tried. Extracorporeal circulatory assist device support has been reported as a rescue therapy in overdose refractory to maximal medical therapy. We report three patients with cardiovascular medication overdose presenting with profound cardiovascular instability refractory to medical therapy. Venoarterial extracorporeal membrane oxygenation support (VA ECMO) was initiated to provide hemodynamic support. Despite the occurrence of device-associated complications, the outcome was good and all patients survived. VA ECMO may be considered in patients with severe refractory shock due to cardiotoxic medication overdose. PMID:29531453

Extracorporeal Membrane Oxygenation in Drug Overdose: A Clinical Case Series.

PubMed

Vignesh, C; Kumar, Madhan; Venkataraman, Ramesh; Rajagopal, Senthilkumar; Ramakrishnan, Nagarajan; Abraham, Babu K

2018-02-01

Overdose of cardiovascular medications such as beta blockers and calcium channel blockers cause impaired cardiac contractility, vasoplegia, and/or rhythm disturbances. In addition to conventional management of limiting absorption, increasing elimination and hemodynamic support intravenous (IV) calcium infusion, hyperinsulinemia-euglycemia therapy, glucagon infusion, and IV lipid emulsion have been tried. Extracorporeal circulatory assist device support has been reported as a rescue therapy in overdose refractory to maximal medical therapy. We report three patients with cardiovascular medication overdose presenting with profound cardiovascular instability refractory to medical therapy. Venoarterial extracorporeal membrane oxygenation support (VA ECMO) was initiated to provide hemodynamic support. Despite the occurrence of device-associated complications, the outcome was good and all patients survived. VA ECMO may be considered in patients with severe refractory shock due to cardiotoxic medication overdose.

[Treatment of refractory status epilepticus with topiramate. Report of three cases].

PubMed

Soler, Bernardita; Godoy, Jaime; Mellado Talesnik, Patricio

2009-07-01

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50%. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

PubMed

Gerlach, Anthony T; Thomas, Sheela; Stawicki, Stanislaw P; Whitmill, Melissa L; Steinberg, Steven M; Cook, Charles H

2011-03-01

In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Case series. Tertiary care surgical intensive care unit. In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Intravenous pyridoxine followed by oral pyridoxine. In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

Medical versus surgical treatment for refractory or recurrent peptic ulcer.

PubMed

Gurusamy, Kurinchi Selvan; Pallari, Elena

2016-03-29

Refractory peptic ulcers are ulcers in the stomach or duodenum that do not heal after eight to 12 weeks of medical treatment or those that are associated with complications despite medical treatment. Recurrent peptic ulcers are peptic ulcers that recur after healing of the ulcer. Given the number of deaths due to peptic ulcer-related complications and the long-term complications of medical treatment (increased incidence of fracture), it is unclear whether medical or surgical intervention is the better treatment option in people with recurrent or refractory peptic ulcers. To assess the benefits and harms of medical versus surgical treatment for people with recurrent or refractory peptic ulcer. We searched the specialised register of the Cochrane Upper GI and Pancreatic Diseases group, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers until September 2015 to identify randomised trials and non-randomised studies, using search strategies. We also searched the references of included studies to identify further studies. We considered randomised controlled trials and non-randomised studies comparing medical treatment with surgical treatment in people with refractory or recurrent peptic ulcer, irrespective of language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We planned to calculate the risk ratio, mean difference, standardised mean difference, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models with Review Manager 5 based on intention-to-treat analysis. We included only one non-randomised study published 30 years ago in the review. This study included 77 participants who had gastric ulcer and in whom medical therapy (histamine H2 receptor blockers, antacids, and diet) had failed after an average duration of treatment of 29 months. The authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality). We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the incidence of complications and gastric cancer (in gastric ulcers only) in recurrent and refractory peptic ulcers. In addition to complications related to treatment and disease, health-related quality of life and loss of productivity should also be measured.

Gender differences in prevalence of psychiatric disorders, levels of alexithymia, and coping strategies in patients with refractory mesial temporal epilepsy and comorbid psychogenic nonepileptic seizures.

PubMed

de Barros, Amanda Cristian Serafim; Furlan, Ana Eliza Romano; Marques, Lucia Helena Neves; de Araújo Filho, Gerardo Maria

2018-05-01

The objective of this study was to investigate the psychological aspects and psychiatric disorders (PDs) in patients dually diagnosed with refractory temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) with psychogenic nonepileptic seizures (PNES) treated in a tertiary center in order to find any gender differences in psychiatric, clinical, and sociodemographic characteristics. Psychiatric assessment was performed through the Diagnostic and Statistical Manual for Psychiatric Disorders - 5th edition (DSM-5). The Brazilian versions of the Medical Outcomes Study 36 (SF-36), Toronto Alexithymia Scale (TAS-20), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), and Ways of Coping Checklist (WCC) were applied. Of the 47 patients enrolled (25 females; 53.2%), females were significantly more likely to have a history of previous psychiatric treatment (P=0.02), family history of epilepsy (P=0.01), and family history of PD (P=0.03). They also presented earlier onset of PNES (P=0.01) and higher PNES duration (P=0.02) compared with males. Major depressive disorder (MDD) was the most frequent PD (24; 51.0%). Females presented more psychiatric diagnoses (P<0.001), more diagnoses of MDD (P<0.001), and posttraumatic stress disorder (PTSD) (P<0.001). Several differences regarding quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies were observed between groups. There are significant gender differences in psychiatric, clinical, and sociodemographic aspects in a group of patients with TLE-MTS and PNES, as well as in quality of life, levels of alexithymia, anxiety/depressive symptoms, and coping strategies. These gender differences suggest that specific approaches might be adopted depending on the patient's gender and, consequently, their distinct psychological/psychiatric profile. Copyright © 2018 Elsevier Inc. All rights reserved.

Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis.

PubMed

Lin, Lung-Chang; Ouyang, Chen-Sen; Chiang, Ching-Tai; Yang, Rei-Cheng; Wu, Rong-Ching; Wu, Hui-Chuan

2014-11-01

Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy.

Emergency Surgery for Refractory Status Epilepticus.

PubMed

Botre, Abhijeet; Udani, Vrajesh; Desai, Neelu; Jagadish, Spoorthy; Sankhe, Milind

2017-08-15

Management of refractory status epilepticus in children is extremely challenging. Two children with medically refractory status epilepticus, both of whom had lesional pathology on MRI and concordant data on EEG and PET scan. Emergency hemispherotomy performed in both patients. A complete, sustained seizure freedom obtained postoperatively. Emergency surgery is a treatment option in selected cases of drug refractory status epilepticus with lesional pathology and concordant data.

Long-term Follow-up of a Case of Gold Shunt Surgery for Refractory Silicone Oil–induced Glaucoma

PubMed Central

Le, Ryan; Berger, Alan R.

2016-01-01

Purpose: To report the first case of gold shunt surgery for treatment of silicone oil–induced refractory glaucoma in a tertiary care academic center, with 5-year follow-up. Design: The study design is a case report. Participants: The participant was a patient who underwent gold shunt surgery. Methods: Institutional Research Ethics Board approval for the study was obtained. A diabetic patient was referred for refractory glaucoma with a history of proliferative diabetic retinal detachment, and surgery with silicone oil. She was uncontrolled on maximal medical therapy and following informed consent, gold shunt surgery was performed. Ocular outcomes and number of medications were reviewed over a 5-year period. Results: Following uncomplicated surgery, intraocular pressure was reduced from 41 to 14 mm Hg, and the number of medications was reduced from 4 to 1. Glaucomatous optic neuropathy remained stable. Conclusions: Gold shunt surgery in this challenging case of silicone oil refractory glaucoma provided long-term intraocular pressure control and reduced need for medication over a 5-year period. PMID:27253968

Urinary urge seizure semiology localization by intracranial monitoring.

PubMed

Rengarajan, Ronak; Shamim, Sadat

2018-01-01

Seizures may present with many different symptom complexes. Seizure semiologies have localization value when contemplating surgical therapies. Epilepsy presenting as a desire to micturate is exceedingly rare, with only a handful of published cases. We present a patient who had initially unexplained childhood urinary urge that progressed into lapses of memory and confusion that was eventually diagnosed as epilepsy in adulthood. Due to refractoriness to medical management, our patient's epileptic focus was localized through both noninvasive and invasive subdural electrode arrays to the nondominant medial temporal lobe and successfully treated with an amygdalohippocampectomy. Only one other case of ictal urinary urgency seizures has been recorded with intracranial electroencephalogram monitoring in the literature.

Temporal lobe neoplasm and seizures: how deep does the story go?

PubMed

Jehi, Lara E; Lüders, Hans O; Naugle, Richard; Ruggieri, Paul; Morris, Harold; Foldvary, Nancy; Wyllie, Elaine; Kotagal, Prakash; Bingaman, Bill; Dinner, Dudley; Prayson, Richard; Diehl, Beate; Alexopoulos, Andreas; Bautista, Jocelyn; Busch, Robyn

2008-03-01

[March 2008-Cleveland Case Report]. There is a well-described association between the occurrence of developmental tumors and the presence of cortical dysplasia in the neighboring brain tissue. The main surgical approaches in the treatment of medically refractory epilepsy related to such developmental tumors include a lesionectomy versus a tailored cortical resection, often guided by an invasive evaluation. This case report describes the surgical management of a 26-year-old female with olfactory auras evolving into automotor seizures and convulsions, occurring in the context of a right temporo-parietal developmental lesion. It illustrates the pros and cons of various surgical approaches, and discusses some pathophysiological aspects of developmental tumors, dysplasia and epilepsy. [Published with video sequences].

Urinary urge seizure semiology localization by intracranial monitoring

PubMed Central

Rengarajan, Ronak; Shamim, Sadat

2018-01-01

ABSTRACT Seizures may present with many different symptom complexes. Seizure semiologies have localization value when contemplating surgical therapies. Epilepsy presenting as a desire to micturate is exceedingly rare, with only a handful of published cases. We present a patient who had initially unexplained childhood urinary urge that progressed into lapses of memory and confusion that was eventually diagnosed as epilepsy in adulthood. Due to refractoriness to medical management, our patient's epileptic focus was localized through both noninvasive and invasive subdural electrode arrays to the nondominant medial temporal lobe and successfully treated with an amygdalohippocampectomy. Only one other case of ictal urinary urgency seizures has been recorded with intracranial electroencephalogram monitoring in the literature. PMID:29686574

Temporal lobe epilepsy in patients with nonlesional MRI and normal memory: an SEEG study.

PubMed

Suresh, Suraj; Sweet, Jennifer; Fastenau, Philip S; Lüders, Hans; Landazuri, Patrick; Miller, Jonathan

2015-12-01

Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and memory deficits is often presumed to have an extramesial or even extratemporal source. In this paper the authors report the results of a comprehensive stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI images and memory scores. Eighteen patients with medically refractory epilepsy who also had unremarkable MR images and normal verbal and visual memory scores on neuropsychological testing were included in the study. All patients had seizure semiology and video electroencephalography (EEG) findings suggestive of TLE. A standardized SEEG investigation was performed for each patient with electrodes implanted into the mesial and lateral temporal lobe, temporal tip, posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate gyrus, and insula. This information was used to plan subsequent surgical management. Interictal SEEG abnormalities were observed in the mesial temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%). Seizure onset was exclusively from mesial structures in 13 (72%), exclusively from lateral temporal cortex and/or temporal tip structures in 2 (11%), and independently from mesial and neocortical foci in 3 (17%). No seizure activity was observed arising from any extratemporal location. All patients underwent surgical intervention targeting the temporal lobe and tailored to the SEEG findings, and all experienced significant improvement in seizure frequency with a postoperative follow-up observation period of at least 1 year. This study demonstrates 3 important findings: 1) normal memory does not preclude mesial temporal seizure onset; 2) onset of seizures exclusively from mesial temporal structures without early neocortical involvement is common, even in the absence of memory deficits; and 3) extratemporal seizure onset is rare when video EEG and semiology are consistent with focal TLE.

Autism in Two Females with Duplications Involving Xp11.22-p11.23

ERIC Educational Resources Information Center

Edens, Anna C.; Lyons, Michael J.; Duron, Reyna M.; DuPont, Barbara R.; Holden, Kenton R.

2011-01-01

We present two phenotypically similar females with Xp duplication who have autism and epilepsy. Case 1 is a 14-year-old Honduran female with autism and medically refractory complex partial, secondarily generalized epilepsy. Case 2 is a 3-year-old Austrian female with autism and medically refractory complex partial epilepsy. Both patients also…

Refractory status epilepticus

PubMed Central

Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M

2014-01-01

Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits. PMID:24791086

Rates and predictors of seizure freedom in resective epilepsy surgery: an update

PubMed Central

Englot, Dario J.; Chang, Edward F.

2017-01-01

Epilepsy is a debilitating neurological disorder affecting approximately 1 % of the world’s population. Drug-resistant focal epilepsies are potentially surgically remediable. Although epilepsy surgery is dramatically underutilized among medically refractory patients, there is an expanding collection of evidence supporting its efficacy which may soon compel a paradigm shift. Of note is that a recent randomized controlled trial demonstrated that early resection leads to considerably better seizure outcomes than continued medical therapy in patients with pharmacoresistant temporal lobe epilepsy. In the present review, we provide a timely update of seizure freedom rates and predictors in resective epilepsy surgery, organized by the distinct pathological entities most commonly observed. Class I evidence, meta-analyses, and individual observational case series are considered, including the experiences of both our institution and others. Overall, resective epilepsy surgery leads to seizure freedom in approximately two thirds of patients with intractable temporal lobe epilepsy and about one half of individuals with focal neocortical epilepsy, although only the former observation is supported by class I evidence. Two common modifiable predictors of postoperative seizure freedom are early operative intervention and, in the case of a discrete lesion, gross total resection. Evidence-based practice guidelines recommend that epilepsy patients who continue to have seizures after trialing two or more medication regimens should be referred to a comprehensive epilepsy center for multidisciplinary evaluation, including surgical consideration. PMID:24497269

Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

PubMed Central

Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

2017-01-01

Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

PubMed

Fabera, Petr; Krijtova, Hana; Tomasek, Martin; Krysl, David; Zamecnik, Josef; Mohapl, Milan; Jiruska, Premysl; Marusic, Petr

2015-09-01

Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Short term outcome of Ahmed glaucoma valve implantation in management of refractory glaucoma in a tertiary hospital in Oman

PubMed Central

Shah, Manali R.; Khandekar, Rajiv B.; Zutshi, Rajiv; Mahrooqi, Rahima

2013-01-01

Background: We present outcomes of Ahmed Glaucoma Valve (AGV) implantation in treating refractory glaucoma in a tertiary hospital in Oman. Refractory glaucoma was defined as previously failed conventional glaucoma surgery and an uncontrolled intraocular pressure (IOP) of more than 21 mm Hg despite treatment with three topical and/or oral therapy. Materials and Methods: This historical cohort study was conducted in 2010. Details of medical and surgical treatment were recorded. Ophthalmologists examined eyes and performed glaucoma surgeries using AGV. The best corrected distant vision, IOP, and glaucoma medications were prospectively reviewed on 1st day, 1st, 6th, 12th week postoperatively, and at the last follow up. Result: Glaucoma specialists examined and treated 40 eyes with refractory glaucoma of 39 patients (20 males + 19 females). Neo-vascular glaucoma was present in 23 eyes. Vision before surgery was <3/60 in 21 eyes. At 12 weeks, one eye had vision better than 6/12, seven eyes had vision 6/18 to 6/60, and eight eyes had vision 6/60 to 3/60. Mean IOP was reduced from 42.9 (SD 16) to 14.2 (SD 8) and 19.1 (SD 7.8) mmHg at one and 12 weeks after surgery, respectively. At 12 weeks, five (12.5%) eyes had IOP controlled without medication. In 33 (77.5%) eyes, pressure was controlled by using one or two eye drops. The mean number of preoperative anti-glaucoma medications (2.38; SD 1.1) was reduced compared to the mean number of postoperative medications (1.92; SD 0.9) at 12 weeks. Conclusion: We succeeded in reducing visual disabilities and the number of anti-glaucoma medications used to treat refractory glaucoma by AGV surgery. PMID:23772122

Office Procedures in Refractory Chronic Rhinosinusitis.

PubMed

Thamboo, Andrew; Patel, Zara M

2017-02-01

Office procedures in chronic rhinosinusitis (CRS) can be considered before and after medical management, as well as before and after surgical management. This article focuses specifically on refractory CRS, meaning those patients who have failed medical and surgical management already. The options available in the management of refractory CRS depend on the personnel, equipment, and instrumentation available in the office setting; surgeon experience; and patient suitability and tolerability. This article provides readers with possible procedural options that can be done in their clinics with indications, patient selection, potential complications, and postoperative considerations. Copyright © 2016 Elsevier Inc. All rights reserved.

Gamma knife radiosurgery for medically and surgically refractory prolactinomas.

PubMed

Pouratian, Nader; Sheehan, Jason; Jagannathan, Jay; Laws, Edward R; Steiner, Ladislau; Vance, Mary L

2006-08-01

Experience with gamma knife radiosurgery (GKRS) for prolactinomas is limited because of the efficacy of medical and surgical intervention. Patients who are refractory to medical and/or surgical therapy may be treated with GKRS. We characterize the efficacy of GKRS for medically and surgically refractory prolactinomas. We reviewed our series of patients with prolactinomas who were treated with GKRS after failing medical and surgical intervention who had at least 1 year of follow-up. Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%). Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most.

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost

PubMed Central

Kurdoğlu, Zehra; Carr, Danielle; Harmouche, Jihad; Ünlü, Serdar; Kılıç, Gökhan S.

2018-01-01

Objective: Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. Material and Methods: We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. Results: Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. Conclusion: PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits. PMID:29503256

Short-term results of the efficacy of percutaneous tibial nerve stimulation on urinary symptoms and its financial cost.

PubMed

Kurdoğlu, Zehra; Carr, Danielle; Harmouche, Jihad; Ünlü, Serdar; Kılıç, Gökhan S

2018-03-01

Overactive bladder (OAB) affects 16.9% of women in the United States. Percutaneous tibial nerve stimulation (PTNS) is a third-line treatment for patients who are refractory to behavioral and pharmacologic therapies. We aimed to evaluate the effects of PTNS on urinary symptoms in patients diagnosed as having refractory OAB and investigate the cost of medications and clinical visits before and after PTNS treatment. We reviewed 60 women with refractory OAB treated with PTNS. Episodes of urinary frequency, leakage, urgency, and nocturia; number of follow-up visits; and medications were recorded. The mean quarterly drug, physician, nurse, and provider costs were calculated. The episodes of urinary symptoms, numbers of follow-up visits, and costs of medications and visits before and after PTNS were compared. Of the 60 patients with refractory OAB, 24 patients who completed 12 weekly sessions of initial PTNS were evaluated. The number of urinary symptoms and follow-up visits significantly decreased after PTNS (p<0.05). The average quarterly medication cost decreased from $656.36±292.45 to $375.51±331.79 after PTNS (p=0.001). After PTNS, quarterly physician and nurse visit costs decreased from $81.73±70.39 to $25.89±54.40 and from $55.23±38.32 to $15.53±19.58, respectively (p<0.05). The quarterly total provider cost was similar before and after PTNS. PTNS treatment significantly improved urinary symptoms of patients with refractory OAB and reduced the costs of medications and physician and nurse visits.

Epileptic phenotype of FGFR3-related bilateral medial temporal lobe dysgenesis.

PubMed

Okazaki, Tetsuya; Saito, Yoshiaki; Ueda, Riyo; Awashima, Takeya; Nishimura, Yoko; Yuasa, Isao; Shinohara, Yuki; Adachi, Kaori; Sasaki, Masayuki; Nanba, Eiji; Maegaki, Yoshihiro

2017-01-01

Hypochondroplasia (HCH) is a skeletal dysplasia, characterized by short stature and macrocephaly. Clinical symptoms and radiological and histopathological features of HCH are similar, but milder than those seen in achondroplasia. Particularly, HCH patients with Asn540Lys mutation in the FGFR3 gene are reported to have medial temporal lobe dysgenesis and epilepsy. We report a 3-year-old girl who developed recurrent epileptic apnea, which started immediately after birth. The apneic seizures were refractory to antiepileptic medications; ictal electroencephalography showed rhythmic activity originating from the left or right temporal areas and rarely from the right frontal area. Macrocephaly was noted since birth. Neuroimaging revealed bilateral dysgenesis and hypometabolism of the medial temporal structures as well as perfusion changes in the left lateral temporofrontal areas during the ictal period. Clonazepam was initiated and acetazolamide dosage was increased at 6months, resulting in complete seizure control after 8months of age. Genetic analysis identified an Asn540Lys (c.1620 C>A) mutation in the FGFR3 gene. Characteristic bone findings on the lumbar spine, iliac bone, and femur were retrospectively confirmed on X-rays during infancy. This was the first report that delineated the epilepsy phenotype in FGFR3-related bilateral medial temporal lobe dysgenesis; such findings would lead to an early diagnosis and better epilepsy management. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Annual Research Progress Report, Fiscal Year 1979,

DTIC Science & Technology

1979-10-01

Chemoimmunotherapy of Carcinoma of the Large 27 Bowel. (T) 77-8 Minoxidil as an Antihypertensive in Patients 29 Refractory to Available Medications. (T) 77-11...INVESTIGATION SERVICE INVESTIGATION PROJECT RESUME TITLE: Minoxidil as an Antihypertensive in Patients Refractory to Available Medications. WORK UNIT...NO: 77-8 (Satellite Protocol of FAMC) PRINCIPAL INVESTIGATOR: James H. Wilkin, MD, LTC, MD OBJECTIVES To test the hypothesis that minoxidil is an

Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis.

PubMed

Vanhaesebrouck, An E; Posch, Barbara; Baker, Sam; Plessas, Ioannis N; Palmer, Anthony C; Constantino-Casas, Fernando

2012-12-01

A 14-year-old male domestic shorthair cat presented with an acute onset of aggressive behaviour, fear and hypersalivation. Neurological examination revealed bilateral mydriasis and left-sided facial twitching and hemiparesis. Magnetic resonance imaging (MRI) showed moderate bilateral symmetrical T2-hyperintensity along the entire hippocampus and bilateral asymmetric T2-hyperintensity in the pyriform lobes. Marked bilateral contrast enhancement of the hippocampus was evident on post-contrast T1-weighted images. The partial complex seizures were refractory to medical treatment and the cat was euthanased 4 days after admission. The clinical and MRI findings were consistent with feline hippocampal necrosis (FHN). On histopathology, neuronal necrosis and astrocytosis were present in the hippocampi and pyriform lobes. In addition, an oligodendroglioma was detected in the right pyriform lobe. Contrary to previous reports of FHN in which no underlying cause could be identified, we believe that in this case the seizure focus arose from a neoplastic lesion within the right pyriform lobe. This unique case report represents the so-called 'dual pathology' of temporal lobe epilepsy in humans, in which an extrahippocampal lesion within the temporal lobe results in hippocampal sclerosis.

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

PubMed

Strauss, Kenneth I; Elisevich, Kost V

2016-10-13

Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1β, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.

Update on New Daily Persistent Headache.

PubMed

Nierenburg, Hida; Newman, Lawrence C

2016-06-01

New daily persistent headache (NDPH) is an uncommon and under-recognized primary headache disorder. Clinically, NDPH may resemble migraine or tension-type headache. Unlike migraine or tension-type headaches, however, a distinguishing feature of NDPH is that the majority of patients with NDPH can pinpoint the exact date of onset of symptoms. While cases can arise de novo, in multiple reports, a viral illness precedes the onset of headache. NDPH has two temporal profiles: a self-limited form that resolves spontaneously without treatment and a refractory, persistent form in which headaches continue unabated for years. Diagnosis is predicated on first eliminating secondary mimics via diagnostic imaging and hematological studies. Lumbar puncture should be considered in patients who are refractory to treatment to search for alterations in CSF pressure or for an infectious process. There have been no randomized clinical trials utilizing acute or preventive therapies for NDPH. In clinical practice, treatment is aimed at matching the predominant headache phenotype; nonetheless, most therapies are generally ineffective or only partially effective. Not surprisingly, medication overuse is very common among patients with this disorder and should be identified, although in most patients, eliminating medication overuse does not alter the course of the illness. There have been reports of successful treatment combining doxycycline 100 mg and montelukast 10 mg, dosed BID for 3 months. Anecdotally, in our practice, this combination has occasionally provided good results. Onabotulinum toxin injections are currently under investigation and may provide a potential new effective treatment regimen.

Daytime outpatient versus inpatient video-EEG monitoring for presurgical evaluation in temporal lobe epilepsy.

PubMed

Guerreiro, Carlos A M; Montenegro, Maria Augusta; Kobayashi, Eliane; Noronha, Ana Lúcia A; Guerreiro, Marilisa M; Cendes, Fernando

2002-06-01

Video-EEG monitoring documentation of seizure localization is one of the most important aspects of a presurgical investigation in refractory temporal lobe epilepsy (TLE) patients. The objective of this study was to evaluate the efficacy of inpatient versus daytime outpatient telemetry. The authors evaluated prospectively 73 patients with medically intractable TLE. Ninety-one telemetry sessions were performed: 35 as inpatients and 56 as outpatients. Outpatient monitoring was performed in the EEG laboratory. They used 18-channel digital EEG. Medications were not changed in the outpatient group. For analysis of the data, time was counted in periods (12 hours = 1 period). Statistical analyses were performed using Student's t-test and the chi2 test. There were no differences between the two groups (outpatient versus inpatient) with respect to age and mean seizure frequency before monitoring, mean time to record the first seizure (1.1 versus 1.4 periods), mean number of seizures per period (0.6 for both groups), lateralization by interictal spiking (46% versus 57%), and lateralization by ictal EEG (59% versus 77%). Daytime outpatient video-EEG monitoring for presurgical evaluation is efficient and comparable with inpatient monitoring. Therefore, the improved cost benefit of outpatient monitoring may increase the access to surgery for individuals with intractable TLE.

Lateralizing value of unilateral relative ictal immobility in patients with refractory focal seizures--Looking beyond unilateral automatisms.

PubMed

Agarwal, Priya; Kaul, Bhavna; Shukla, Garima; Srivastava, Achal; Singh, Mamta Bhushan; Goyal, Vinay; Behari, Madhuri; Suri, Ashish; Gupta, Aditya; Garg, Ajay; Gaikwad, Shailesh; Bal, C S

2015-12-01

Ictal motor phenomena play a crucial role in the localization of seizure focus in the management of refractory focal epilepsy. While the importance of unilateral automatisms is well established, little attention is paid to the contralateral relatively immobile limb. In cases where automatisms mimic clonic or dystonic movements and in the absence of previously well-established signs, unilateral relative ictal immobility (RII) is potentially useful as a lateralizing sign. This study was carried out to examine the lateralizing value of this sign and to define its characteristics among patients of refractory focal epilepsy. VEEGs of 69 consecutive patients of refractory focal epilepsy who had undergone epilepsy surgery at our center over last four years were reviewed and analyzed for the presence of RII. Unilateral RII was defined as a paucity of movement in one limb lasting for at least 10s while the contralateral limb showed purposive or semi-purposive movements (in the absence of tonic or dystonic posturing or clonic movements in the involved limb). The findings were seen in the light of VEEG, radiological and nuclear imaging data, and with post-surgical outcome. Unilateral RII as a lateralizing sign was found in 24 of 69 patients (34.78%), consisting of both temporal and extra temporal epilepsy, with 100% concordance with VEEG and MRI data. All patients demonstrating this sign had a good post-surgical outcome. RII, when well characterized is a frequent and reliable lateralizing sign in patients of refractory focal epilepsy. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Dietary therapy is not the best option for refractory nonsurgical epilepsy.

PubMed

Vaccarezza, María Magdalena; Silva, Walter Horacio

2015-09-01

The ketogenic diet (KD) is currently a well-established treatment for patients with medically refractory, nonsurgical epilepsy. However, despite its efficacy, the KD is highly restrictive and constitutes a treatment with serious potential adverse effects, and often with difficulties in its implementation and compliance. Patients on the KD require strict follow-up and constant supervision by a medical team highly experienced in its management in order to prevent complications. Other alternative treatments for patients with refractory epilepsy include vagus nerve stimulation (VNS), new-generation antiepileptic drugs (AEDs), corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this review, we explain not only the difficulties of the KD as a therapeutic option for refractory epilepsy but also the benefits of other therapeutic strategies, which, in many cases, have proven to have better efficacy than the KD itself. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Coexistence of meningoencephalocele and hippocampal sclerosis: a new type of dual pathology.

PubMed

Martinoni, Matteo; Marucci, Gianluca; Gagliardini, Gabriele; Tinuper, Paolo; Michelucci, Roberto; Giulioni, Marco

2017-05-01

Both temporal lobe meningoencephalocele (TE) and hippocampal sclerosis (HS) are causes of drug-resistant temporal lobe epilepsy. Spontaneous TE constitutes a rare but well-known and increasingly recognised cause of refractory epilepsy. It is well known that HS may be associated with another neocortical lesion (dual pathology). Here we report for the first time a new type of dual pathology; namely, the coexistence of temporal pole meningoencephalocele and HS.

Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: a chart review study.

PubMed

Adler, Benjamin A; Wink, Logan K; Early, Maureen; Shaffer, Rebecca; Minshawi, Noha; McDougle, Christopher J; Erickson, Craig A

2015-01-01

Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain. © The Author(s) 2014.

Relationship of number of seizures recorded on video-EEG to surgical outcome in refractory medial temporal lobe epilepsy

PubMed Central

Sainju, Rup Kamal; Wolf, Bethany Jacobs; Bonilha, Leonardo; Martz, Gabriel

2014-01-01

Introduction Surgical planning for refractory medial temporal lobe epilepsy (rMTLE) relies on seizure localization by ictal electroencephalography (EEG). Multiple factors impact the number of seizures recorded. We evaluated whether seizure freedom correlated to the number of seizures recorded, and the related factors. Methods We collected data for 32 patients with rMTLE who underwent anterior temporal lobectomy. Primary analysis evaluated number of seizures captured as a predictor of surgical outcome. Subsequent analyses explored factors that may seizure number. Results Number of seizures recorded did not predict seizure freedom. More seizures were recorded with more days of seizure occurrence (p<0.001), seizure clusters (p≤0.011) and poorly localized seizures (PLSz) (p=0.004). Regression modeling showed a trend for subjects with fewer recorded poorly localized seizures to have better surgical outcome (p=0.052). Conclusions Total number of recorded seizures does not predict surgical outcome. Patients with more PLSz may have worse outcome. PMID:22990726

Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.

PubMed

Ganguli, Malika P; Upton, Adrian R M; Kamath, Markad V

2017-01-01

Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

Presurgical evaluation for partial epilepsy: Relative contributions of chronic depth-electrode recordings versus FDG-PET and scalp-sphenoidal ictal EEG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engel, J. Jr.; Henry, T.R.; Risinger, M.W.

1990-11-01

One hundred fifty-three patients with medically refractory partial epilepsy underwent chronic stereotactic depth-electrode EEG (SEEG) evaluations after being studied by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and scalp-sphenoidal EEG telemetry. We carried out retrospective standardized reviews of local cerebral metabolism and scalp-sphenoidal ictal onsets to determine when SEEG recordings revealed additional useful information. FDG-PET localization was misleading in only 3 patients with temporal lobe SEEG ictal onsets for whom extratemporal or contralateral hypometabolism could be attributed to obvious nonepileptic structural defects. Two patients with predominantly temporal hypometabolism may have had frontal epileptogenic regions, but ultimate localization remains uncertain. Scalp-sphenoidalmore » ictal onsets were misleading in 5 patients. For 37 patients with congruent focal scalp-sphenoidal ictal onsets and temporal hypometabolic zones, SEEG recordings never demonstrated extratemporal or contralateral epileptogenic regions; however, 3 of these patients had nondiagnostic SEEG evaluations. The results of subsequent subdural grid recordings indicated that at least 1 of these patients may have been denied beneficial surgery as a result of an equivocal SEEG evaluation. Weighing risks and benefits, it is concluded that anterior temporal lobectomy is justified without chronic intracranial recording when specific criteria for focal scalp-sphenoidal ictal EEG onsets are met, localized hypometabolism predominantly involves the same temporal lobe, and no other conflicting information has been obtained from additional tests of focal functional deficit, structural imaging, or seizure semiology.« less

Treatment responsive GABA(B)-receptor limbic encephalitis presenting as new-onset super-refractory status epilepticus (NORSE) in a deployed U.S. soldier.

PubMed

Hainsworth, Jeffrey Brian; Shishido, Akira; Theeler, Brett James; Carroll, Craig Grason; Fasano, Rebecca Ellen

2014-12-01

A 23-year-old, previously healthy, deployed U.S. soldier presented with bilateral temporal lobe seizures recalcitrant to multiple antiepileptic drugs and anti-seizure anaesthetic agents. He received methylprednisolone, intravenous immunoglobulins, plasma exchange, and rituximab for presumed autoimmune encephalitis before achieving seizure freedom. Six weeks after presentation, the aetiology of his refractory seizures was found to be due to autoantibodies targeting the anti-GABA(B)-receptor. This case is noteworthy for being the first reported case of anti-GABA(B)-receptor limbic encephalitis presenting with new-onset refractory status epilepticus (NORSE), a clinical syndrome that often carries a grave prognosis and in which a treatable aetiology is often never discovered. Our case also supports testing for GABA-receptor autoantibodies and the upfront use of multi-modal immunotherapy in patients presenting with limbic encephalitis and new refractory seizures.

Effect of Continued Medical Therapy on Productivity Costs for Refractory Chronic Rhinosinusitis.

PubMed

Rudmik, Luke; Soler, Zachary M; Smith, Timothy L; Mace, Jess C; Schlosser, Rodney J; DeConde, Adam S

2015-11-01

It is estimated that lost productivity related to chronic rhinosinusitis (CRS) costs society in excess of $13 billion per year in the United States. Given this tremendous cost to society, it is important to evaluate the effect of current interventions on improving this productivity loss. To define the change in productivity costs in patients with refractory CRS who select continued medical therapy. Observational cohort study. Thirty-eight patients with a guideline-based diagnosis of CRS whose initial appropriate medical therapy failed were enrolled from 4 tertiary-level rhinology clinics. The study was conducted from December 6, 2010, to April 23, 2013, and data analysis was performed from December 6, 2010, to June 1, 2015. Continued medical therapy for CRS. The human capital approach was applied to quantify productivity costs. Absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time, which was measured at enrollment (baseline) and at a minimum of 6 months after treatment. Lost productive time was monetized using the annual daily wage rates obtained from the 2012 US National Census and the 2013 US Department of Labor statistics. Thirty-eight patients with refractory CRS who selected continued medical therapy had a mean (SD) baseline annual productivity cost of $3464 ($4900) per patient. After continued medical therapy for a mean of 12.8 (4.8) months, productivity costs were $2730 ($3720) (before vs after continued medical therapy productivity cost, P = .74). Mean annual absenteeism was reduced from 5 (12) days to 2 (8) days (P = .02). Mean annual presenteeism (17 [27] days reduced to 15 [23] days; P = .93) and mean annual household days lost (7 [7] days reduced to 6 [6] days; P = .51) were maintained at baseline levels. There were no significant differences in productivity outcomes based on endoscopy, the 22-item Sinonasal Outcome Test score, age, or polyp status (all P ≥ .11). Patients with refractory CRS often make treatment decisions based on the degree of quality-of-life and productivity impairment. Outcomes from this study suggest that productivity in patients with refractory CRS who have minor reductions in baseline productivity can remain stable with continued medical therapy. Physicians can use this information to inform appropriate patients with CRS of their expected outcomes from continued medical therapy.

Temporal lobe origin is common in patients who have undergone epilepsy surgery for hypermotor seizures.

PubMed

Arain, Amir M; Azar, Nabil J; Lagrange, Andre H; McLean, Michael; Singh, Pradumna; Sonmezturk, Hasan; Konrad, Peter; Neimat, Joseph; Abou-Khalil, Bassel

2016-11-01

Hypermotor seizures are most often reported from the frontal lobe but may also have temporal, parietal, or insular origin. We noted a higher proportion of patients with temporal lobe epilepsy in our surgical cohort who had hypermotor seizures. We evaluated the anatomic localization and surgical outcome in patient with refractory hypermotor seizures who had epilepsy surgery in our center. We identified twenty three patients with refractory hypermotor seizures from our epilepsy surgery database. We analyzed demographics, presurgical evaluation including semiology, MRI, PET scan, interictal/ictal scalp video-EEG, intracranial recording, and surgical outcomes. We evaluated preoperative variables as predictors of outcome. Most patients (65%) had normal brain MRI. Intracranial EEG was required in 20 patients (86.9%). Based on the presurgical evaluation, the resection was anterior temporal in fourteen patients, orbitofrontal in four patients, cingulate in four patients, and temporoparietal in one patient. The median duration of follow-up after surgery was 76.4months. Fourteen patients (60%) had been seizure free at the last follow up while 3 patients had rare disabling seizures. Hypermotor seizures often originated from the temporal lobe in this series of patients who had epilepsy surgery. This large proportion of temporal lobe epilepsy may be the result of a selection bias, due to easier localization and expected better outcome in temporal lobe epilepsy. With extensive presurgical evaluation, including intracranial EEG when needed, seizure freedom can be expected in the majority of patients. Copyright © 2016. Published by Elsevier Inc.

Neuromodulation for cephalgias

PubMed Central

Rasskazoff, Serge Y.; Slavin, Konstantin V.

2013-01-01

Headaches (cephalgias) are a common reason for patients to seek medical care. There are groups of patients with recurrent headache and craniofacial pain presenting with malignant course of their disease that becomes refractory to pharmacotherapy and other medical management options. Neuromodulation can be a viable treatment modality for at least some of these patients. We review the available evidence related to the use of neuromodulation modalities for the treatment of medically refractory craniofacial pain of different nosology based on the International Classification of Headache Disorders, 2nd edition (ICHD-II) classification. This article also reviews the scientific rationale of neuromodulation application in management of cephalgias. PMID:23682340

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review

PubMed Central

Alswat, Khaled A.

2015-01-01

Patient: Female, 52 Final Diagnosis: Refractory iodine induced hyperthyroidism Symptoms: Neck swelling • shortness of breath Medication: Cholestyramine Clinical Procedure: Total thyroidectomy Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. Case Report: A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Conclusions: Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine. PMID:26207323

Interfacing sensory input with motor output: does the control architecture converge to a serial process along a single channel?

PubMed Central

van de Kamp, Cornelis; Gawthrop, Peter J.; Gollee, Henrik; Lakie, Martin; Loram, Ian D.

2013-01-01

Modular organization in control architecture may underlie the versatility of human motor control; but the nature of the interface relating sensory input through task-selection in the space of performance variables to control actions in the space of the elemental variables is currently unknown. Our central question is whether the control architecture converges to a serial process along a single channel? In discrete reaction time experiments, psychologists have firmly associated a serial single channel hypothesis with refractoriness and response selection [psychological refractory period (PRP)]. Recently, we developed a methodology and evidence identifying refractoriness in sustained control of an external single degree-of-freedom system. We hypothesize that multi-segmental whole-body control also shows refractoriness. Eight participants controlled their whole body to ensure a head marker tracked a target as fast and accurately as possible. Analysis showed enhanced delays in response to stimuli with close temporal proximity to the preceding stimulus. Consistent with our preceding work, this evidence is incompatible with control as a linear time invariant process. This evidence is consistent with a single-channel serial ballistic process within the intermittent control paradigm with an intermittent interval of around 0.5 s. A control architecture reproducing intentional human movement control must reproduce refractoriness. Intermittent control is designed to provide computational time for an online optimization process and is appropriate for flexible adaptive control. For human motor control we suggest that parallel sensory input converges to a serial, single channel process involving planning, selection, and temporal inhibition of alternative responses prior to low dimensional motor output. Such design could aid robots to reproduce the flexibility of human control. PMID:23675342

Initial Clinical Experience with Ahmed Valve Implantation in Refractory Pediatric Glaucoma

PubMed

Novak-Lauš, Katia; Škunca Herman, Jelena; Šimić Prskalo, Marija; Jurišić, Darija; Mandić, Zdravko

2016-12-01

The purpose is to report on the safety and efficacy of Ahmed Glaucoma Valve (AGV, New World Medical, Inc., Rancho Cucamonga, CA, USA) implantation for the management of refractory pediatric glaucoma observed during one-year follow up period. A retrospective chart review was conducted on 10 eyes, all younger than 11 years, with pediatric glaucoma that underwent AGV implantation for medicamentously uncontrolled intraocular pressure (IOP) between 2010 and 2014. Outcome measures were control of IOP below 23 mm Hg (with or without antiglaucoma medications) and changes in visual acuity. Complications were recorded. After AGV implantation, IOP values ranged from 18 mm Hg to 23 mm Hg (except for one eye with postoperative hypotonia due to suprachoroid hemorrhage, where the postoperative IOP value was 4 mm Hg). The number of antiglaucoma medications was reduced, i.e. four patients had two medications, one patient had one medication, and the others did not need antiglaucoma medication on the last follow-up visit. One eye had suprachoroid hemorrhage, one eye had long-term persistent uveitic membrane, and two eyes had tube-cornea touch. In conclusion, AGV implantation appears to be a viable option for the management of refractory pediatric glaucoma and shows success in IOP control. However, there was a relatively high complication rate limiting the overall success rate.

Ablation and pacing: improving brain perfusion and cognitive function in patients with atrial fibrillation and uncontrolled ventricular rates.

PubMed

Efimova, Irina; Efimova, Nataliya; Chernov, Vladimir; Popov, Sergey; Lishmanov, Yuri

2012-03-01

The aim of our study was to determine if ablation and pacing improved brain perfusion (BP) and cognitive function (CF) in patients with medically refractory rapidly conducted atrial fibrillation (Med Refr RCAF). The study included 17 patients with Med Refr RCAF (average age 55.3 ± 4.5 years). All patients underwent brain single photon emission computed tomography scanning with (99m) Tc-hexamethylpropylene amine oxime and comprehensive neuropsychological testing before and after 3 months following pacemaker implantation. The BP was significantly lower in all regions in patients with Med Refr RCAF compared with the control group. The greatest BP decrease was revealed in the inferior frontal (P = 0.002) and posterior parietal (P = 0.024) brain regions. These patients showed cognitive deficit in 94%. There was a direct correlation between BP and CF parameters. Ablation followed by pacemaker implantation had a positive effect on BP and CF in all patients with Med Refr RCAF. Thus, BP increased in the right inferior frontal (P = 0.01), in the left superior frontal (P = 0.007), and in the left temporal (P = 0.005) cortex. These patients demonstrated improvements in immediate and delayed verbal memory, immediate and delayed visual memory, abstract mentation, attention, psychomotor speed, as well as in learning. Patients with atrial fibrillation and rapid ventricular rates refractory to medical treatment have marked signs of brain hypoperfusion and impaired CF. Ablation and pacing improve left ventricular systolic function, thereby increasing BP and improving CF. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

Molecular-level dynamics of refractory dissolved organic matter

NASA Astrophysics Data System (ADS)

Niggemann, J.; Gerdts, G.; Dittmar, T.

2012-04-01

Refractory dissolved organic matter (DOM) accounts for most of the global oceanic organic carbon inventory. Processes leading to its formation and factors determining its stability are still largely unknown. We hypothesize that refractory DOM carries a universal molecular signature. Characterizing spatial and temporal variability in this universal signature is a key to understanding dynamics of refractory DOM. We present results from a long-term study of the DOM geo-metabolome in the open North Sea. Geo-metabolomics considers the entity of DOM as a population of compounds, each characterized by a specific function and reactivity in the cycling of energy and elements. Ten-thousands of molecular formulae were identified in DOM by ultrahigh resolution mass spectrometry analysis (FT-ICR-MS, Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry). The DOM pool in the North Sea was influenced by a complex interplay of processes that produced, transformed and degraded dissolved molecules. We identified a stable fraction in North Sea DOM with a molecular composition similar to deep ocean DOM. Molecular-level changes in this stable fraction provide novel information on dynamics and interactions of refractory DOM.

Initial clinical experience of tube-shunt surgery in Ethiopian patients with refractory glaucoma.

PubMed

T/Giorgis, Abeba

2012-04-01

In Ethiopia, it is not uncommon to encounter refractory glaucoma cases that could be managed with tube-shunt surgery. Tube-shunt implant surgery has been a standard procedure option and widely used for various forms of refractory glaucoma. To described the initial experience and outcome of Ahmed Tube shunt implant for refractory adult Ethiopian glaucoma cases. Retrospective review of consecutive adult patients with refractory glaucoma who underwent Ahmed glaucoma valve implant at the Department of ophthalmology, Menelik II Hospital, Addis Ababa between April 2009 and December 2010. intraocular pressure (IOP), visual acuity, use of supplemental medical therapy and surgical complications. Success was defined as IOP greater than 5 and less than 22 mmHg with at least 30% reduction in IOP from preoperative levels with and without supplemental glaucoma medications, no additional surgeries to lower the IOP and without visual loss of light perception from devastating postoperative complications. Thirteen eyes of 12 patients (10 men, 2 women; mean age 52.4 +/- 15. 7) who underwent glaucoma tube-shunt drainage surgery with Ahmed-tube valve were included in this analysis. The mean preoperative IOP was 31.38 +/- 8.67 mmHg with 2.23 +/- 0.44 antiglaucoma medications. Postoperatively, the mean IOP reduced to 15.52 +/- 8.80 mmHg at 1 week, 14.77 +/- 6.39 mmHg at 1 month, 16.62 +/- 4.48 mmHg at 3 months, and 17.15 +/- 3.87 mmHg at 6 months. The reduction from the preoperative mean IOP at last follow up was 45.3% with 1.08 +/- 0.44 supplemental glaucoma medications. The success rate of IOP controlling according to the definition was 76.9%. The pressure remained below 18 mmHg with and without medication in 9/13 (69.2%) eyes, while three eyes required no medication at all till the last follow-up with sustained IOP < 15 mmHg. At the last follow-up the visual acuity reduced by > or = 2 lines in two eyes while one patient's vision worsened from counting finger of one meter to hand movement. Visual improvement of one and two lines documented in two eyes. Hypotony, Tube-corneal touch, acceleration of cataract, choroidal effusion, flat anterior chamber, visual reduction and tube exposure were the types of complications encountered in 6 eyes, while 3 eyes had more than one complication. The study has shown that tube-shunt implant to be effective in lowering intraocular pressure in refractory glaucoma cases. The few cases reported are indicators of the importance of the procedure in salvaging vision of patients with refractory glaucoma and the need of large scale prospective study in the country.

Laser ablation therapy: An alternative treatment for medically resistant mesial temporal lobe epilepsy after age 50.

PubMed

Waseem, Hena; Osborn, Katie E; Schoenberg, Mike R; Kelley, Valerie; Bozorg, Ali; Cabello, Daniel; Benbadis, Selim R; Vale, Fernando L

2015-10-01

Selective anterior mesial temporal lobe (AMTL) resection is considered a safe and effective treatment for medically refractory mesial temporal lobe epilepsy (MTLE). However, as with any open surgical procedure, older patients (aged 50+) face greater risks. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has shown recent potential as an alternative treatment for MTLE. As a less invasive procedure, MRgLITT could be particularly beneficial to older patients. To our knowledge, no study has evaluated the safety and efficacy of MRgLITT in this population. Seven consecutive patients (aged 50+) undergoing MRgLITT for MTLE were followed prospectively to assess surgical time, complications, postoperative pain control, length of stay (LOS), operating room (OR) charges, total hospitalization charges, and seizure outcome. Five of these patients were assessed at the 1-year follow-up for seizure outcome. These data were compared with data taken from 7 consecutive patients (aged 50+) undergoing AMTL resection. Both groups were of comparable age (mean: 60.7 (MRgLITT) vs. 53 (AMTL)). One AMTL resection patient had a complication of aseptic meningitis. One MRgLITT patient experienced an early postoperative seizure, and two MRgLITT patients had a partial visual field deficit. Seizure-freedom rates were comparable (80% (MRgLITT) and 100% (AMTL) (p>0.05)) beyond 1year postsurgery (mean follow-up: 1.0years (MRgLITT) vs. 1.8years (AMTL)). Mean LOS was shorter in the MRgLITT group (1.3days vs. 2.6days (p<0.05)). Neuropsychological outcomes were comparable. Short-term follow-up suggests that MRgLITT is safe and provides outcomes comparable to AMTL resection in this population. It also decreases pain medication requirement and reduces LOS. Further studies are necessary to assess the long-term efficacy of the procedure. Copyright © 2015 Elsevier Inc. All rights reserved.

Refractory status epilepticus complicated by drug-induced involuntary movements.

PubMed

Nair, Pradeep Pankajakshan; Wadwekar, Vaibhav; Murgai, Aditya; Narayan, Sunil K

2014-02-11

New onset refractory status epilepticus (NORSE) is a neurological emergency and difficult to treat condition. We report a case of involuntary movements resulting from thiopentone sodium infusion during the management of refractory status epilepticus. A young woman was admitted with fever and NORSE in the neurology intensive care unit. In addition to supportive measures, she was treated with intravenous lorazepam, phenytoin sodium, sodium valproate, midazolam and thiopentone sodium. While on thiopentone sodium, she developed involuntary twitches involving her upper limbs and face with EEG showing no evidence of ongoing status epilepticus. Because of the temporal relationship with thiopentone infusion, we tapered the dose of thiopentone sodium, which resulted in the disappearance of the movements. The patient recovered well with no recurrence of the seizures during the hospital stay.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients.

PubMed

Doucet, Gaelle E; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.

Frontal gray matter abnormalities predict seizure outcome in refractory temporal lobe epilepsy patients

PubMed Central

Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.

2015-01-01

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates. PMID:26594628

H.M. never again! An analysis of H.M.'s epilepsy and treatment.

PubMed

Mauguière, F; Corkin, S

2015-03-01

On August 25, 1953, the patient H.M., aged 27, underwent a bilateral surgical destruction of the inner aspect of his temporal lobes performed by William Beecher Scoville with the aim to control H.M.'s drug refractory epileptic seizures and alleviate their impact on his quality of life. Postoperatively, H.M. presented for 55 years a "striking and totally unexpected grave loss of recent memories". This paper reports what we know about H.M.'s epilepsy before and after surgery and puts forward arguments supporting the syndromic classification of his epilepsy. We attempted to elucidate what could have been the rationale, in 1953, of Scoville's decision to carry out a bilateral ablation of H.M.'s medial temporal lobe structures, and we examined whether there was any convincing argument published before 1953 suggesting that bilateral hippocampal ablation could result in a permanent and severe amnesia. Our a posteriori analysis of H.M.'s medical history suggested that he was most probably suffering from idiopathic generalized epilepsy with absences and generalized convulsive seizures worsened by high dosage phenytoin treatment, or less probably from cryptogenic frontal lobe epilepsy. Importantly, he did not have temporal lobe epilepsy. Scoville based his proposal of bilateral mesial temporal lobe ablation on his experience as a psychosurgeon and on the assumption that the threshold of generalized epileptic activity could be lowered by some kind of hippocampal dysfunction potentially epileptic in nature. Given the scanty information on the link between amnesia and medial temporal lobe lesions that was available in humans in 1953, one can understand why Scoville was so surprised by the "striking and totally unexpected" memory loss he observed in H.M. after the bilateral ablation of his mesial temporal lobe structures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Minimally invasive surgical approaches for temporal lobe epilepsy

PubMed Central

Chang, Edward F.; Englot, Dario J.; Vadera, Sumeet

2016-01-01

Surgery can be a highly effective treatment for medically refractory temporal lobe epilepsy (TLE). The emergence of minimally invasive resective and nonresective treatment options has led to interest in epilepsy surgery among patients and providers. Nevertheless, not all procedures are appropriate for all patients, and it is critical to consider seizure outcomes with each of these approaches, as seizure freedom is the greatest predictor of patient quality of life. Standard anterior temporal lobectomy (ATL) remains the gold standard in the treatment of TLE, with seizure freedom resulting in 60–80% of patients. It is currently the only resective epilepsy surgery supported by randomized controlled trials and offers the best protection against lateral temporal seizure onset. Selective amygdalohippocampectomy techniques preserve the lateral cortex and temporal stem to varying degrees and can result in favorable rates of seizure freedom but the risk of recurrent seizures appears slightly greater than with ATL, and it is not clear whether neuropsychological outcomes are improved with selective approaches. Stereotactic radiosurgery presents an opportunity to avoid surgery altogether, with seizure outcomes now under investigation. Stereotactic laser thermo-ablation allows destruction of the mesial temporal structures with low complication rates and minimal recovery time, and outcomes are also under study. Finally, while neuromodulatory devices such as responsive neurostimulation, vagus nerve stimulation, and deep brain stimulation have a role in the treatment of certain patients, these remain palliative procedures for those who are not candidates for resection or ablation, as complete seizure freedom rates are low. Further development and investigation of both established and novel strategies for the surgical treatment of TLE will be critical moving forward, given the significant burden of this disease. PMID:26017774

Abnormal behavior in children with temporal lobe epilepsy and ganglioglioma.

PubMed

Guimarães, Catarina A; Franzon, Renata C; Souza, Elisabete A P; Schmutzler, Kátia M R S; Montenegro, Maria Augusta; Queiroz, Luciano de S; Cendes, Fernando; Guerreiro, Marilisa M

2004-10-01

Temporal lobe epilepsy in childhood is characterized by great clinical, electroencephalographic, and etiological diversity. The prognosis after temporal lobe epilepsy surgery in childhood is usually good, with most patients achieving complete seizure control. However, in some children behavior deteriorates postoperatively. We report two girls (2 and 6 years of age) with refractory seizures due to temporal lobe ganglioglioma. They exhibited aggression and hyperactivity since the beginning of their epilepsy. In both patients, behavioral disturbances worsened postoperatively, despite complete seizure control. Patients and parents should be advised about possible behavioral disturbances after epilepsy surgery, especially in the presence of a temporal lobe developmental tumor, even when seizure control is achieved postoperatively.

Evaluation of Hospitalized Intractable Epileptic Children with SPECT Scan in Ahvaz, South West of Iran

PubMed Central

Ahmadi, Faramarz; Malekian, Arash; Davoodzadeh, Hannaneh; Kabirinia, Hossein

2016-01-01

Introduction Seizures are the most frequent neurologic disorder seen in childhood. Epilepsy is a group of disorders that includes an abnormally increased susceptibility to seizures. Aim To examine the effectiveness of SPECT (Single Photon Emission Computerized Tomography) in detecting seizure foci in 21 Iranian children who had medically refractory epilepsy. Materials and Methods Children between 2 to 15 years of age with uncontrolled seizures were investigated using SPECT scan as a standardized protocol. Results In 16 cases (76.2%), likely seizure foci were evident, as were seen in the form of decreased regional blood flow, while in 5 cases (23.8%), SPECT scan results were normal. Left temporal lobe was the most common area which had decreased regional blood flow. Conclusion SPECT scan can potentially be used to investigate children with uncontrolled seizures. PMID:27891419

Cost reduction with maintenance ECT in refractory bipolar disorder.

PubMed

Bonds, C; Frye, M A; Coudreaut, M F; Cunningham, M; Spearing, M; McGuire, M; Guze, B

1998-03-01

A case report of outpatient maintenance electroconvulsive therapy (ECT) is presented in a patient with bipolar disorder type I refractory to conventional medication treatment but responsive to ECT. A cost comparison is made showing substantial savings when outpatient maintenance ECT is used in lieu of inpatient hospitalization with ECT. A detailed life chart illustrating multiple medication trials that failed to stabilize the patient accompanies the financial summary. This case highlights the advantages of outpatient maintenance ECT for bipolar depression particularly with regard to safety, efficacy, and significant health care cost reduction.

Response properties of the refractory auditory nerve fiber.

PubMed

Miller, C A; Abbas, P J; Robinson, B K

2001-09-01

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

Dietary therapy is the best option for refractory nonsurgical epilepsy.

PubMed

Felton, Elizabeth A; Cervenka, Mackenzie C

2015-09-01

Ketogenic diet therapies for epilepsy have been described since the fifth century and published in scientific literature since the early 1900s. Since that time, the diet's popularity has waxed and waned as newer drugs and other treatments have been introduced. However, in recent years, dietary therapy for epilepsy has been increasingly accepted by physicians and desired by patients as an alternative to new drugs and neurostimulation. The introduction of less restrictive versions of the classic ketogenic diet, such as the modified Atkins diet (MAD), have led to increased numbers of adult patients with refractory epilepsy who are initiating dietary treatment. Approximately half of adults and children who start a ketogenic diet have a >50% seizure reduction, which is impressive given that these patients typically have medically refractory epilepsy. We believe that ketogenic dietary treatment is the best option for children and adults with refractory nonsurgical epilepsy due to its efficacy, rapid seizure reduction, synergistic effects with other antiseizure treatments, known and treatable side effects, potential to treat comorbid medical conditions, and worldwide availability. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Status Epilepticus and Refractory Status Epilepticus Management

PubMed Central

Abend, Nicholas S.; Bearden, David; Helbig, Ingo; McGuire, Jennifer; Narula, Sona; Panzer, Jessica A.; Topjian, Alexis; Dlugos, Dennis J.

2014-01-01

Status epilepticus (SE) describes persistent or recurring seizures without a return to baseline mental status, and is a common neurologic emergency. SE can occur in the context of epilepsy or may be symptomatic of a wide range of underlying etiologies. The clinician’s aim is to rapidly institute care that simultaneously stabilizes the patient medically, identifies and manages any precipitant conditions, and terminates seizures. Seizure management involves “emergent” treatment with benzodiazepines followed by “urgent” therapy with other anti-seizure medications. If seizures persist then refractory SE is diagnosed and management options include additional anti-seizure medications or infusions of midazolam or pentobarbital. This paper reviews the management of pediatric SE and RSE. PMID:25727508

Neuroimaging evaluation in refractory epilepsy

PubMed Central

Granados, Ana M; Orejuela, Juan F

2015-01-01

Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

PubMed

Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

New-onset refractory status epilepticus

PubMed Central

Foreman, Brandon P.; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C.; Jongeling, Amy C.; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F.; Schmitt, Sarah E.; Gerard, Elizabeth E.; Gofton, Teneille; Kaplan, Peter W.; Lee, Jong W.; Legros, Benjamin; Szaflarski, Jerzy P.; Westover, Brandon M.; LaRoche, Suzette M.; Hirsch, Lawrence J.

2015-01-01

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. PMID:26296517

Severe and Refractory Hypertension in a Young Woman

PubMed Central

Cuadra, René H; White, William B

2016-01-01

Background Refractory hypertension in a young person is an uncommon clinical problem, but one that may be referred to hypertension specialists. Factitious hypertension is fortunately quite rare, but should be considered when evaluating patients who are refractory to numerous classes of antihypertensive therapies and have failed to achieve control despite input from multiple providers. Report of a Case A 19 year old woman was referred to us after failing to achieve blood pressure control by a primary physician and 2 subspecialists in nephrology and hypertension; she also had numerous emergency department visits for symptomatic and severe hypertension. Exhaustive diagnostic testing for secondary causes and witnessed medication dosing in an outpatient setting was unrevealing. Subsequent inpatient admission demonstrated normalization of BPs with small doses of intravenous antihypertensive agents. During the hospitalization, she was observed “pocketing” her oral medications in the buccal folds, and then discarding them in a trash container. Confrontation by psychiatrists and the hypertension specialists led to the admission that she had learned to start and stop beta-blockers and clonidine to induce severe, rebound hypertension. Discussion Factitious and induced hypertension is a rare cause of resistant or refractory hypertension. Nevertheless, hypertension specialists should suspect the diagnosis when there is a history of visits to multiple institutions and physicians, negative secondary workup, absence of overt target organ damage, history of psychiatric illness, and employment in the medical field. PMID:27160032

Occipital Nerve Stimulation for the Treatment of Patients With Medically Refractory Occipital Neuralgia: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline.

PubMed

Sweet, Jennifer A; Mitchell, Laura S; Narouze, Samer; Sharan, Ashwini D; Falowski, Steven M; Schwalb, Jason M; Machado, Andre; Rosenow, Joshua M; Petersen, Erika A; Hayek, Salim M; Arle, Jeffrey E; Pilitsis, Julie G

2015-09-01

Occipital neuralgia (ON) is a disorder characterized by sharp, electrical, paroxysmal pain, originating from the occiput and extending along the posterior scalp, in the distribution of the greater, lesser, and/or third occipital nerve. Occipital nerve stimulation (ONS) constitutes a promising therapy for medically refractory ON because it is reversible with minimal side effects and has shown continued efficacy with long-term follow-up. To conduct a systematic literature review and provide treatment recommendations for the use of ONS for the treatment of patients with medically refractory ON. A systematic literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and April 2014 using MeSH headings and keywords relevant to ONS as a means to treat ON. A second literature search was conducted using the PubMed database and the Cochrane Library to locate articles published between 1966 and June 2014 using MeSH headings and keywords relevant to interventions that predict response to ONS in ON. The strength of evidence of each article that underwent full text review and the resulting strength of recommendation were graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. Nine studies met the criteria for inclusion in this guideline. All articles provided Class III Level evidence. Based on the data derived from this systematic literature review, the following Level III recommendation can be made: the use of ONS is a treatment option for patients with medically refractory ON.

Tailored unilobar and multilobar resections for orbitofrontal-plus epilepsy.

PubMed

Serletis, Demitre; Bulacio, Juan; Alexopoulos, Andreas; Najm, Imad; Bingaman, William; González-Martínez, Jorge

2014-10-01

Surgery for frontal lobe epilepsy often has poor results, likely because of incomplete resection of the epileptogenic zone. To present our experience with a series of patients manifesting 2 different anatomo-electro-clinical patterns of refractory orbitofrontal epilepsy, necessitating different surgical approaches for resection in each group. Eleven patients with refractory epilepsy involving the orbitofrontal region were consecutively identified over 3 years in whom stereoelectroencephalography identified the epileptogenic zone. All patients underwent preoperative evaluation, stereoelectroencephalography, and postoperative magnetic resonance imaging. Demographic features, seizure semiology, imaging characteristics, location of the epileptogenic zone, surgical resection site, and pathological diagnosis were analyzed. Surgical outcome was correlated with type of resection. Five patients exhibited orbitofrontal plus frontal epilepsy with the epileptogenic zone consistently residing in the frontal lobe; after surgery, 4 patients were free of disabling seizures (Engel I) and 1 patient improved (Engel II). The remaining 6 patients had multilobar epilepsy with the epileptogenic zone located in the orbitofrontal cortex associated with the temporal polar region (orbitofrontal plus temporal polar epilepsy). After surgery, all 6 patients were free of disabling seizures (Engel I). Pathology confirmed focal cortical dysplasia in all patients. We report no complications or mortalities in this series. Our findings highlight the importance of differentiating between orbitofrontal plus frontal and orbitofrontal plus temporal polar epilepsy in patients afflicted with seizures involving the orbitofrontal cortex. For identified cases of orbitofrontal plus temporal polar epilepsy, a multilobar resection including the temporal pole may lead to improved postoperative outcomes with minimal morbidity or mortality.

[Impact of topical application of autologous platelet-rich gel on medical expenditure and length of stay in hospitals in diabetic patients with refractory cutaneous ulcers].

PubMed

Li, Lan; Wang, Chun; Wang, Yan; He, Li-Ping; Yang, Yan-Zhi; Chen, Li-Hong; Chen, Da-Wei; Li, Xiu-Jun; Ran, Xing-Wu

2012-09-01

To evaluate the potential financial benefit of topical application of autologous platelet-rich gel (APG) in treating diabetic refractory cutaneous ulcers. A single-center prospective randomized controlled trial was undertaken, with 117 patients with proven diabetic refractory cutaneous ulcers participating in the study. The patients who gave informed consents were randomly assigned into standard care group (n = 58) or standard care plus topical application of APG treatment group (n = 59). The outcome of healing and the medical expenditur and length of stay in the patients were compared between the two groups. The APG-treated group had better healing outcomes than the standard-treated group. The APG-treated group had 84.750 (50/59) complete healing and 98.31% improvement, higher than the 68.97% (40/58) and 75.86%, respectively, in the standard-treated group (P = 0.026). The median length for healing in the APG-treated patients was 36 days, shorter than the 45 days in the standard-treated patients (P = 0.012). The total medical expenditure and length of stay in hospitals were not significantly different between APG-treated patients [yen 38223 (23070-57398); 57 (41-94) days] and standard-treated patients [yen 35070 (24436-53649); 58 (31.75-58.50) days) (P = 0.455 and 0.301 respectively). Spendings on items such as medicine, artificial treatment, materials, interventional operation, surgical procedures, laboratory tests and other auxiliary examination, accommodations, meals, nursing care and debridement and dressing change were similar between the two groups (P > 0.05). There is an advantage for the topical application of APG on diabetic refractory cutaneous ulcers in terms of the healing outcomes. APG is a cost-effective choice for patients with diabetic refractory cutaneous ulcers.

Patients' perceptions of memory functioning before and after surgical intervention to treat medically refractory epilepsy.

PubMed

Lineweaver, Tara T; Naugle, Richard I; Cafaro, Alyce M; Bingaman, William; Lüders, Hans O

2004-12-01

One risk associated with epilepsy surgery is memory loss, but perhaps more important is how patients perceive changes in their memories. This longitudinal study evaluated changes in memory self-reports and investigated how self-reports relate to changes on objective memory measures in temporal or extratemporal epilepsy patients who underwent surgery. Objective memory (Wechsler Memory Scale-Revised) and subjective memory self-reports (Memory Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients approximately 6 months before and 6 months after surgery. A measure of depressive affect (Beck Depression Inventory-2nd Edition) was used to control variance attributable to emotional distress. Despite a lack of significant correlational relationships between objective and subjective memory for the entire sample, significant correlations between objective memory scores and self-reports did emerge for a subset of patients who evidenced memory decline. Differences also were found in the subjective memory ratings of temporal lobe versus extratemporal patients. Temporal lobe patients rated their memories more negatively than did extratemporal patients and were more likely to report significant improvements in their memory after surgery. In general, patients were not accurate when rating their memories compared to other adults. However, patients with significant declines in their memories were sensitive to actual changes in their memories over time relative to their own personal baselines.

[Clinical and pathological definition of temporal medium epilepsy subtypes with hypocampic sclerosis].

PubMed

Olivares-Granados, Gonzalo; Ríos-Pelegrina, Rosa María; Ruiz-Giménez, Jesús; Galdón-Castillo, Alberto; Escobar-Delgado, Teresa; García Del Moral, Raimundo

Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). At 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). The results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Interictal spiking increases with sleep depth in temporal lobe epilepsy.

PubMed

Malow, B A; Lin, X; Kushwaha, R; Aldrich, M S

1998-12-01

To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. At the time of study, subjects were seizure-free for > or =24 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.

When all seems lost: management of refractory constipation-Surgery, rectal irrigation, percutaneous endoscopic colostomy, and more.

PubMed

Wilkinson-Smith, V; Bharucha, A E; Emmanuel, A; Knowles, C; Yiannakou, Y; Corsetti, M

2018-05-01

While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited. © 2018 John Wiley & Sons Ltd.

Updates in Refractory Status Epilepticus

PubMed Central

Mahulikar, Advait; Suchdev, Kushak; Shah, Aashit

2018-01-01

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status. PMID:29854452

What is the full range of medical and surgical treatments available for patients with Eustachian tube dysfunction?

PubMed

Adil, Eelam; Poe, Dennis

2014-02-01

To present the current medical and surgical treatment options for Eustachian tube dysfunction. Balloon dilation or microdebrider Eustachian tuboplasty are feasible treatment options for patients with refractory dilatory dysfunction as an alternative to tympanostomy tube placement. There is increasing evidence that repair of patulous Eustachian tubes by the insertion of a shim or fat graft reconstruction within the lumen of the Eustachian tube orifice may be effective. In patients with Eustachian tube dysfunction that is refractory to medical management, newer surgical techniques may provide symptomatic relief with a reasonable duration. Continued basic science research into the cause of dysfunction, the mechanisms of benefit from intervention and long-term clinical outcomes are necessary.

Economic Evaluation of Endoscopic Sinus Surgery versus Continued Medical Therapy for Refractory Chronic Rhinosinusitis

PubMed Central

Rudmik, Luke; Soler, Zachary M.; Mace, Jess C.; Schlosser, Rodney J.; Smith, Timothy L.

2014-01-01

Objective To evaluate the long-term cost-effectiveness of endoscopic sinus surgery (ESS) compared to continued medical therapy for patients with refractory chronic rhinosinusitis (CRS). Study Design Cohort-style Markov decision tree economic evaluation Methods The economic perspective was the US third party payer with a 30 year time horizon. The two comparative treatment strategies were: 1) ESS followed by appropriate postoperative medical therapy and 2) continued medical therapy alone. Primary outcome was the incremental cost per quality adjusted life year (QALY). Costs were discounted at a rate of 3.5% in the reference case. Multiple sensitivity analyses were performed including differing time-horizons, discounting scenarios, and a probabilistic sensitivity analysis (PSA). Results The reference case demonstrated that the ESS strategy cost a total of $48,838.38 and produced a total of 20.50 QALYs. The medical therapy alone strategy cost a total of $28,948.98 and produced a total of 17.13 QALYs. The incremental cost effectiveness ratio (ICER) for ESS versus medical therapy alone is $5,901.90 per QALY. The cost-effectiveness acceptability curve from the PSA demonstrated that there is 74% certainty that the ESS strategy is the most cost-effective decision for any willingness to pay threshold greater then $25,000. The time horizon analysis suggests that ESS becomes the cost-effective intervention within the 3rd year after surgery. Conclusion Results from this study suggest that employing an ESS treatment strategy is the most cost-effective intervention compared to continued medical therapy alone for the long-term management of patients with refractory CRS. PMID:25186499

Improvement in Hemodynamics After Methylene Blue Administration in Drug-Induced Vasodilatory Shock: A Case Report.

PubMed

Laes, JoAn R; Williams, David M; Cole, Jon B

2015-12-01

The purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient. This is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg. Methylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies.

Mesial temporal lobe epilepsy diminishes functional connectivity during emotion perception.

PubMed

Steiger, Bettina K; Muller, Angela M; Spirig, Esther; Toller, Gianina; Jokeit, Hennric

2017-08-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with impaired recognition of emotional facial expressions. Correspondingly, imaging studies showed decreased activity of the amygdala and cortical face processing regions in response to emotional faces. However, functional connectivity among regions involved in emotion perception has not been studied so far. To address this, we examined intrinsic functional connectivity (FC) modulated by the perception of dynamic fearful faces among the amygdala and limbic, frontal, temporal and brainstem regions. Regions of interest were identified in an activation analysis by presenting a block-design with dynamic fearful faces and dynamic landscapes to 15 healthy individuals. This led to 10 predominately right-hemispheric regions. Functional connectivity between these regions during the perception of fearful faces was examined in drug-refractory patients with left- (n=16) or right-sided (n=17) MTLE, epilepsy patients with extratemporal seizure onset (n=15) and a second group of 15 healthy controls. Healthy controls showed a widespread functional network modulated by the perception of fearful faces that encompassed bilateral amygdalae, limbic, cortical, subcortical and brainstem regions. In patients with left MTLE, a downsized network of frontal and temporal regions centered on the right amygdala was present. Patients with right MTLE showed almost no significant functional connectivity. A maintained network in the epilepsy control group indicates that findings in mesial temporal lobe epilepsy could not be explained by clinical factors such as seizures and antiepileptic medication. Functional networks underlying facial emotion perception are considerably changed in left and right MTLE. Alterations are present for both hemispheres in either MTLE group, but are more pronounced in right MTLE. Disruption of the functional network architecture possibly contributes to deficits in facial emotion recognition frequently reported in MTLE. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of histopathologic subtype in the setting of hippocampal sclerosis-associated mesial temporal lobe epilepsy.

PubMed

Gales, Jordan M; Jehi, Lara; Nowacki, Amy; Prayson, Richard A

2017-05-01

Hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) are among the most common neuropathological findings in those undergoing surgery for refractory mesial temporal lobe epilepsy. Existing data regarding differences among the most recent International League Against Epilepsy (ILAE) HS subtypes remain limited. This study sought to characterize the roles of HS subtype and coexistent FCD. Epilepsy surgery pathologic specimens in 307 cases of temporal lobe epilepsy with HS were reviewed (mean age±SD, 37±15years; 56% women). HS and coexistent FCD were classified according to ILAE guidelines. Medical records were reviewed for data on seizure recurrence and seizure burden (clinical follow-up mean duration ± SD, 5±4years). Cases of typical HS (ILAE type I) predominated (ILAE type Ia: 41%, Ib: 47%, II: 11%, and III: 0.7%]. The HS subtypes shared similar demographic and etiologic characteristics, as well as associated pathology and postoperative seizure outcomes. Individuals with type Ib HS were more likely to remain seizure free at long-term follow-up when compared with other subtypes, and they had a later age of seizure onset. Two hundred forty-three cases (79%) demonstrated FCD within the adjacent temporal lobe. Its presence was associated with a significantly decreased risk of seizure recurrence (P=.02). When present, FCD was predominantly type I (98%). HS subtype does not appear to affect epilepsy surgery outcomes despite some clinical differences between the subgroups. FCD is often observed in association with HS in mesial temporal lobe epilepsy; the finding of FCD was associated with better postoperative outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

PubMed Central

Tang, Fei; Hartz, Anika M. S.; Bauer, Björn

2017-01-01

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy. PMID:28729850

[Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

PubMed

Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

2004-12-01

Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

Unusual Clinical Presentation and Role of Decompressive Craniectomy in Herpes Simplex Encephalitis.

PubMed

Singhi, Pratibha; Saini, Arushi Gahlot; Sahu, Jitendra Kumar; Kumar, Nuthan; Vyas, Sameer; Vasishta, Rakesh Kumar; Aggarwal, Ashish

2015-08-01

Decompressive craniectomy in pediatric central nervous infections with refractory intracranial hypertension is less commonly practiced. We describe improved outcome of decompressive craniectomy in a 7-year-old boy with severe herpes simplex encephalitis and medically refractory intracranial hypertension, along with a brief review of the literature. Timely recognition of refractory intracranial hypertension and surgical decompression in children with herpes simplex encephalitis can be life-saving. Additionally, strokelike atypical presentations are being increasingly recognized in children with herpes simplex encephalitis and should not take one away from the underlying herpes simplex encephalitis. © The Author(s) 2014.

Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome.

PubMed

Schoenberg, Mike R; Maddux, Brian N; Riley, David E; Whitney, Christina M; Ogrocki, Paula K; Gould, Deborah; Maciunas, Robert J

2015-02-01

Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. Average age was 28.2 years (SD = 7.5) with 12-17 years of education. Participants were disabled by tics, with a tic frequency of 50-80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive-compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. Bilateral centromedian-parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved. © 2014 International Neuromodulation Society.

The impact of family factors on IQ in pediatric medically refractory epilepsy.

PubMed

Puka, Klajdi; Smith, Mary Lou; Widjaja, Elysa

2017-02-01

To evaluate whether family factors were associated with intellectual functioning among children with medically refractory epilepsy, and whether family factors moderate the relationship between patient/epilepsy-related variables and intellectual functioning. Children aged 4 to 18 years with medically refractory epilepsy who were evaluated for surgical candidacy were recruited. The authors assessed the association of intellectual quotient (IQ) with patient, epilepsy, and family factors. Family factors included parental education, household income, and validated parent-report measures of family functioning, family mastery and social support, and family demands. Univariable analyses showed that higher IQ scores were associated with an older age of epilepsy onset (β = .260, p = .009), fewer antiepileptic drugs (β = .248, p = .013), a shorter duration (β = .384, p < .001) and percentage of life with epilepsy (β = .419, p < .001), unilobar epileptogenic foci relative to multilobar foci (β = .274, p = .006), and lower family demands (β = .211, p = .035). In multivariable analysis, unilobar epileptogenic foci (p = .010) and a shorter percentage of life with epilepsy (p = .001) remained significant predictors of IQ. Exploratory moderation analyses found the relationship between the extent of epileptogenic foci and IQ to be moderated by family demands (p = .004); specifically, patients with unilobar epileptogenic onset had similar IQ scores irrespective of family demands, whereas patients with multilobar foci had lower IQ scores with increasing family demands. Family factors did not have a large impact on IQ among children with medically refractory epilepsy, although the moderating effect of family demands deserves further study. Epilepsy-related factors in this patient group may weaken the link between child IQ and family factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The long-term outcomes of epilepsy surgery

PubMed Central

Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Objective Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. Methods This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. Results We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1–27). Kaplan-Meier estimates showed that 47% (95% CI 40–58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31–45) at 10 years after surgery. 74% (95% CI 69–80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64–77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. Conclusion The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections. PMID:29768433

The long-term outcomes of epilepsy surgery.

PubMed

Mohan, Midhun; Keller, Simon; Nicolson, Andrew; Biswas, Shubhabrata; Smith, David; Osman Farah, Jibril; Eldridge, Paul; Wieshmann, Udo

2018-01-01

Despite modern anti-epileptic drug treatment, approximately 30% of epilepsies remain medically refractory and for these patients, epilepsy surgery may be a treatment option. There have been numerous studies demonstrating good outcome of epilepsy surgery in the short to median term however, there are a limited number of studies looking at the long-term outcomes. The aim of this study was to ascertain the long-term outcome of resective epilepsy surgery in a large neurosurgery hospital in the U.K. This a retrospective analysis of prospectively collected data. We used the 2001 International League Against Epilepsy (ILAE) classification system to classify seizure freedom and Kaplan-Meier survival analysis to estimate the probability of seizure freedom. We included 284 patients who underwent epilepsy surgery (178 anterior temporal lobe resections, 37 selective amygdalohippocampectomies, 33 temporal lesionectomies, 36 extratemporal lesionectomies), and had a prospective median follow-up of 5 years (range 1-27). Kaplan-Meier estimates showed that 47% (95% CI 40-58) remained seizure free (apart from simple partial seizures) at 5 years and 38% (95% CI 31-45) at 10 years after surgery. 74% (95% CI 69-80) had a greater than 50% seizure reduction at 5 years and 70% (95% CI 64-77) at 10 years. Patients who had an amygdalohippocampectomy were more likely to have seizure recurrence than patients who had an anterior temporal lobe resection (p = 0.006) and temporal lesionectomy (p = 0.029). There was no significant difference between extra temporal and temporal lesionectomies. Hippocampal sclerosis was associated with a good outcome but declined in relative frequency over the years. The vast majority of patients who were not seizure free experienced at least a substantial and long-lasting reduction in seizure frequency. A positive long-term outcome after epilepsy surgery is possible for many patients and especially those with hippocampal sclerosis or those who had anterior temporal lobe resections.

The Influence of refractoriness upon comprehension of non-verbal auditory stimuli.

PubMed

Crutch, Sebastian J; Warrington, Elizabeth K

2008-01-01

An investigation of non-verbal auditory comprehension in two patients with global aphasia following stroke is reported. The primary aim of the investigation was to establish whether refractory access disorders can affect non-verbal input modalities. All previous reports of refractoriness, a cognitive syndrome characterized by response inconsistency, sensitivity to temporal factors and insensitivity to item frequency, have involved comprehension tasks which have a verbal component. Two main experiments are described. The first consists of a novel sound-to-picture and sound-to-word matching task in which comprehension of environmental sounds is probed under conditions of semantic relatedness and semantic unrelatedness. In addition to the two stroke patients, the performance of a group of 10 control patients with non-vascular pathology is reported, along with evidence of semantic relatedness effects in sound comprehension. The second experiment examines environmental sound comprehension within a repetitive probing paradigm which affords assessment of the effects of semantic relatedness, response consistency and presentation rate. It is demonstrated that the two stroke patients show a significant increase in error rate across multiple probes of the same set of sound stimuli, indicating the presence of refractoriness within this non-verbal domain. The implications of the results are discussed with reference to our current understanding of the mechanisms of refractoriness.

Long-term treatment of epilepsy with everolimus in tuberous sclerosis

PubMed Central

Wilfong, Angus A.; Mays, Maxwell; Talley, Christina M.; Agricola, Karen; Tudor, Cindy; Capal, Jamie; Holland-Bouley, Katherine; Franz, David Neal

2016-01-01

Objective: To evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC). Methods: Everolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life. Results: Of the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months. Conclusions: Improved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC. Classification of evidence: This study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control. PMID:27815402

Emerging treatment options for refractory angina pectoris: ranolazine, shock wave treatment, and cell-based therapies.

PubMed

Gennari, Marco; Gambini, Elisa; Bassetti, Beatrice; Capogrossi, Maurizio; Pompilio, Giulio

2014-01-01

A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris, a clinical condition characterized by severe angina despite optimal medical therapy. These patients are not candidates for surgical or percutaneous revascularization. Herein we review the most up-to-date information regarding the modern approach to the patient with refractory angina pectoris, from conventional medical management to new medications and shock wave therapy, focusing on the use of endothelial precursor cells (EPCs) in the treatment of this condition. Clinical limitations of the efficiency of conventional approaches justify the search for new therapeutic options. Regenerative medicine is considered the next step in the evolution of organ replacement therapy. It is driven largely by the same health needs as transplantation and replacement therapies, but it aims further than traditional approaches, such as cell-based therapy. Increasing knowledge of the role of circulating cells derived from bone marrow (EPCs) on cardiovascular homeostasis in physiologic and pathologic conditions has prompted the clinical use of these cells to relieve ischemia. The current state of therapeutic angiogenesis still leaves many questions unanswered. It is of paramount importance that the treatment is delivered safely. Direct intramyocardial and intracoronary administration has demonstrated acceptable safety profiles in early trials, and may represent a major advance over surgical thoracotomy. The combined efforts of bench and clinical researchers will ultimately answer the question of whether cell therapy is a suitable strategy for treatment of patients with refractory angina.

Surgical interventions in patients with chronic constipation refractory to intensive medical treatment.

PubMed

Yalcin, Samet; Yalcin, Bulent; Gecim, Ethem I

2009-01-01

Management of patients with chronic constipation (CC), irresponsive to medical treatment, is very difficult. There are some surgical approaches reported for the treatment. In this study we aimed to assess the results of different surgical procedures in patients with severe CC who were refractory to intensive medical treatments. Fifteen patients with refractory chronic constipation underwent surgical management between 1998 and 2003 in Ankara University School of Medicine Department of General Surgery. Median age of the patients was 40 years (range, 24-77), female/male ratio was 11/4, median duration of symptoms was 13 years (range, 4-35 years) and median interval of two subsequent bowel movements was 15 (range, 5-30) days. Preoperative evaluation including barium enema, colonoscopy, colonic transit time, and cinedefecography and balloon expulsion test were done in all patients. Clinical analysis of constipation with these tests indicated a simple slow transit colon in three patients but more complicated variations of combined anatomical functional disorders in the rest of the cases. Surgical procedures consisted of total colectomy, Frykman-Goldberg procedure, Wells procedure and appendisostomy, laparoscopically in 8 of them. Deep vein thrombosis developed in the postoperative period after rectopexy and pelvic floor repair in one case. The median follow-up time was 5.5 years. Fourteen (93.3%) patients had an excellent bowel movement and were highly satisfied with the surgical management. Surgical interventions may be beneficial in selected patients with refractory chronic constipation (Tab. 2, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor.

PubMed

Resnick, Andrew S; Okun, Michael S; Malapira, Teresita; Smith, Donald; Vale, Fernando L; Sullivan, Kelly; Miller, Amber; Jahan, Israt; Zesiewicz, Theresa

2012-01-01

Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. The data from this study indicate that medication cessation is common following unilateral DBS for ET.

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor

PubMed Central

Resnick, Andrew S.; Okun, Michael S.; Malapira, Teresita; Smith, Donald; Vale, Fernando L.; Sullivan, Kelly; Miller, Amber; Jahan, Israt; Zesiewicz, Theresa

2012-01-01

Background Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. Methods We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Results Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. Discussion The data from this study indicate that medication cessation is common following unilateral DBS for ET. PMID:23440408

LINX®, a novel treatment for patients with refractory asthma complicated by gastroesophageal reflux disease: a case report.

PubMed

Sriratanaviriyakul, Narin; Kivler, Celeste; Vidovszky, Tamas J; Yoneda, Ken Y; Kenyon, Nicholas J; Murin, Susan; Louie, Samuel

2016-05-24

Gastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure. Our patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5 years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting β2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting. LINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children.

PubMed

Mutalib, Mohamed; Borrelli, Osvaldo; Blackstock, Sarah; Kiparissi, Fevronia; Elawad, Mamoun; Shah, Neil; Lindley, Keith

2014-12-01

Management of refractory inflammatory bowel disease (IBD) in children is challenging and once response to conventional medical therapy deviates from the expected, options are often limited. Sirolimus is commonly used in post-transplantation management and is used sparsely as rescue therapy in refractory Crohn's disease. In the present study, we report the efficacy of sirolimus as an adjuvant immunosuppressive therapy in a retrospective case review of a selected group of IBD children who were refractory to the conventional treatments. Medical records of children with refractory IBD unresponsive to conventional therapy and started on sirolimus between 2006 and 2012 were retrospectively reviewed. Clinical response, through Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI), as well as intestinal inflammation, through specific histological scores, was evaluated. The records of 14 patients were analyzed. Eleven of them had ulcerative colitis (UC) and 3 Crohn's disease (CD); mean age at diagnosis was 9.1 years (standard deviation 3.8). Of UC patients, 5 (45%) achieved clinical remission and 2 (18%) showed clinical response. All CD patients went into clinical remission. Mucosal healing was achieved by 5 children (45%) with UC and 2 (67%) with CD patients. One child with ulcerative colitis was weaned off adalimumab, while 2 children with CD were weaned off prednisolone and methotrexate successfully. Our data provide evidence that sirolimus seems to be effective as rescue therapy in a subgroup of children with severe IBD refractory to conventional therapies by inducing both clinical remission and mucosal healing. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review.

PubMed

Alswat, Khaled A

2015-07-24

Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine.

A UK trial-based cost--utility analysis of transmyocardial laser revascularization compared to continued medical therapy for treatment of refractory angina pectoris.

PubMed

Campbell, H E; Tait, S; Buxton, M J; Sharples, L D; Caine, N; Schofield, P M; Wallwork, J

2001-08-01

Transmyocardial laser revascularization (TMLR) is used to treat patients with refractory angina considered unsuitable for conventional forms of revascularization. Using patient specific data from a single centre UK randomised-controlled trial, we aimed to determine whether, from a UK National Health Service (NHS) perspective, TMLR plus standard medical management is cost-effective when compared with standard medical management alone. One hundred and eighty-eight patients assessed as having refractory angina, and not suitable for conventional forms of revascularization were randomized to receive TMLR and medical management (94) or medical management alone (94). Costs to the UK NHS of TMLR (where appropriate), and all secondary sector health care contacts and cardiac-related medication in the 12 months following randomization, were collected. Patient utility as measured using the EuroQol EQ-5D questionnaire was combined with 12-month survival data to generate quality adjusted life years (QALYs). The mean cost per patient over the year from hospitalization for TMLR was 11,470 pounds sterling and for medical management alone was 2586 pounds sterling, giving a cost difference of 8901 pounds sterling (95% confidence interval (CI) 7502 pounds sterling--10,008 pounds sterling: P < 0.0001). The mean QALY difference, in favour of TMLR was 0.039 (95% CI -0.033 to 0.113: P = 0.268). This gives an incremental cost per QALY of over 228,000 pounds sterling. Analysis of stochastic uncertainty and of sensitivity to gross changes in key parameters consistently produces very high costs per QALY. The policy implications are clear: for such patients TMLR is an inefficient use of UK health service resources. This conclusion would not be changed by considerable improvements in effectiveness or reductions in cost.

Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management

PubMed Central

Lv, Han-Jing; Qiu, Zhong-Min

2015-01-01

Refractory chronic cough due to gastroesophageal reflux is a troublesome condition unresponsive to the standard medical anti-reflux therapy. Its underlying mechanisms may include incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations and esophageal hypersensitivity. The diagnosis of this disorder depends on both the findings of multi-channel intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux therapy. The strategies of pharmacological treatment for refractory chronic cough due to reflux include the optimization of proton pump inhibitors and add-on therapies with histamine H2 receptor antagonists, baclofen and gabapentin. However, the further study is needed to satisfy its management. PMID:26413488

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

PubMed

Ordás, I; Domènech, E; Mañosa, M; García-Sánchez, V; Iglesias-Flores, E; Rodríguez-Moranta, F; Márquez, L; Merino, O; Fernández-Bañares, F; Gomollón, F; Vera, M; Gutiérrez, A; LLaó, J; Gisbert, J P; Aguas, M; Arias, L; Rodríguez-Lago, I; Muñoz, C; Alcaide, N; Calvet, X; Rodríguez, C; Montoro, M A; García, S; De Castro, M L; Piqueras, M; Pareja, L; Ribes, J; Panés, J; Esteve, M

2018-05-01

Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Revision with Totally Hand-Sewn Gastrojejunostomy and Vagotomy for Refractory Marginal Ulcer after Laparoscopic Roux-en-Y Gastric Bypass.

PubMed

Chang, Po-Chih; Huang, Chih-Kun; Rajan, Mahendra; Hsin, Ming-Che

2016-05-01

Marginal ulcer is not infrequent after laparoscopic Roux-en-Y gastric bypass and could result in undesirable complications, such as intractability, bleeding, or perforation. Those patients who failed medical therapy, regarded as refractory marginal ulcers, may be considered as candidates for revisional surgery. Herein, we make a video presentation of a laparoscopic revisional procedure for refractory marginal ulcer. A 29-year-old morbidly obese woman (initial body mass index 37.1 kg/m(2)), a non-smoker, presented with persistent epigastric pain 3 months after initial laparoscopic Roux-en-Y gastric bypass at another institution. After an exhaustive work-up there, only the gastroendoscopy revealed a marginal ulcer and she underwent medical treatment (proton pump inhibitor and sucralfate) for 3 months, but the patient's symptom aggravated and the serial gastroendoscopies still confirmed the marginal ulcer without obvious resolution after a total of 4 months proton pump inhibitor therapy, suggesting failure of medical treatment and intractability. Laparoscopic revisional procedure with totally hand-sewn gastrojejunostomy and vagotomy was performed to relieve her intractable condition. The procedure took 130 min, without any intra-operative complications. Blood loss was 80 mL. The patient had an uneventful postoperative course, and the postoperative hospital stay was 3 days. She was relieved of her symptoms after this revisional surgery, and a subsequent gastroendoscopy 15 months later showed no marginal ulcers. Though long-term follow-up is needed to draw a definite conclusion, totally hand-sewn gastrojejunostomy and vagotomy remains a practicable revisional procedure to relieve refractory marginal ulcers.

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

PubMed

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

Refractory myasthenia gravis – clinical profile, comorbidities and response to rituximab

PubMed Central

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079

High pre-transplant serum nitrate levels predict risk of acute steroid-refractory graft-versus-host disease in the absence of statin therapy

PubMed Central

Dietrich, Sascha; Okun, Jürgen G.; Schmidt, Kathrin; Falk, Christine S.; Wagner, Andreas H.; Karamustafa, Suzan; Radujkovic, Aleksandar; Hegenbart, Ute; Ho, Anthony D.; Dreger, Peter; Luft, Thomas

2014-01-01

Steroid-refractory graft-versus-host disease is a life-threatening complication after allogeneic stem cell transplantation. Evidence is accumulating that steroid-refractory graft-versus-host disease is associated with endothelial distress. Endothelial cell homeostasis is regulated by nitric oxide, and serum nitrates are derived from nitric oxide synthase activity or dietary sources. In this retrospective study based on 417 patients allografted at our institution we investigated whether quantification of serum nitrates could predict steroid-refractory graft-versus-host disease. Elevated pre-transplant levels of serum nitrates (>26.5 μM) predicted steroid-refractory graft-versus-host disease (P=0.026) and non-relapse mortality (P=0.028), particularly in combination with high pre-transplant angiopoietin-2 levels (P=0.0007 and P=0.021, respectively). Multivariate analyses confirmed serum nitrates as independent predictors of steroid-refractory graft-versus-host disease and non-relapse mortality. Differences in serum nitrate levels did not correlate with serum levels of tumor necrosis factor or C-reactive protein or expression of inducible nitric oxide synthase in blood cells. Patients with high pre-transplant nitrate levels had significantly reduced rates of refractory graft-versus-host disease (P=0.031) when pravastatin was taken. In summary, patients at high risk of developing steroid-refractory graft-versus-host disease could be identified prior to transplantation by serum markers linked to endothelial cell function. Retrospectively, statin medication was associated with a reduced incidence of refractory graft-versus-host disease in this endothelial high-risk cohort. PMID:24142995

MRI-negative temporal lobe epilepsy-What do we know?

PubMed

Muhlhofer, Wolfgang; Tan, Yee-Leng; Mueller, Susanne G; Knowlton, Robert

2017-05-01

Temporal lobe epilepsy (TLE) is the most common focal epilepsy in adults. TLE has a high chance of becoming medically refractory, and as such, is frequently considered for further evaluation and surgical intervention. Up to 30% of TLE cases, however, can have normal ("nonlesional" or negative) magnetic resonance imaging (MRI) results, which complicates the presurgical workup and has been associated with worse surgical outcomes. Helped by contributions from advanced imaging techniques and electrical source localization, the number of surgeries performed on MRI-negative TLE has increased over the last decade. Thereby new epidemiologic, clinical, electrophysiologic, neuropathologic, and surgical data of MRI-negative TLE has emerged, showing characteristics that are distinct from those of lesional TLE. This review article summarizes what we know today about MRI-negative TLE, and discusses the comprehensive assessment of patients with MRI-negative TLE in a structured and systematic approach. It also includes a concise description of the most recent developments in structural and functional imaging, and highlights postprocessing imaging techniques that have been shown to add localization value in MRI-negative epilepsies. We evaluate surgical outcomes of MRI-negative TLE, identify prognostic makers of postoperative seizure freedom, and discuss strategies for optimizing the selection of surgical candidates in this group. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

PubMed

Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

2012-05-01

Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range <2), and bilateral symmetrical temporal lobe hemorrhages and thalamic changes on cranial MRI. She developed multifocal and myoclonic seizures refractory to multiple antiepileptic drugs that responded to pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study.

PubMed

Friesecke, Sigrun; Stecher, Stephanie-Susanne; Gross, Stefan; Felix, Stephan B; Nierhaus, Axel

2017-09-01

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90-100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb ® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (-0.4 µg/kg/min; p = 0.03) and 12 h (-0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.

Efficacy of infliximab rescue therapy in patients with chronic refractory pouchitis: a multicenter study.

PubMed

Barreiro-de Acosta, M; García-Bosch, O; Souto, R; Mañosa, M; Miranda, J; García-Sanchez, V; Gordillo, J; Chacon, S; Loras, C; Carpio, D; Maroto, N; Menchén, L; Rojas-Feria, M; Sierra, M; Villoria, A; Marin-Jimenez, I

2012-05-01

Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Maintenance ECT as a therapeutic approach to medication-refractory epilepsy in an adult with mental retardation: case report and review of literature.

PubMed

Shah, Nilesh; Pande, Nikhil; Bhat, Tushar; Murke, Mukund; Andrade, Chittaranjan

2012-06-01

Electroconvulsive therapy (ECT) raises the seizure threshold. This physiological change may benefit patients with seizure disorders. Whereas ECT has recently been used to terminate medication-refractory status epilepticus, there is little current literature on its planned administration as a specific maintenance treatment for medication-refractory epilepsy. We used maintenance ECT to treat an 18-year-old man with a long-standing generalized tonic-clonic seizure disorder who had shown poor response to several antiepileptic drugs administered in combination with antiepileptic medication compliance confirmed through drug level monitoring. A total of 52 ECTs were administered across nearly 20 months at a mean frequency of once in nearly 12 days. From the very outset, ECT dramatically decreased the frequency of spontaneous seizures from approximately 6 to 24 per week at baseline to approximately 1 to 2 per week after ECT initiation. The efficacy of maintenance ECT in spontaneous seizure prophylaxis was greater when the ECT treatment interval was narrower. Improvement with ECT was associated with improved behavior and improved psychosocial functioning on clinical report. No cognitive or other adverse effects were reported or clinically ascertained. The ECT charge administered at the last 10 treatment sessions was 1434 millicoulombs. This is probably the highest electrical stimulus dose recorded in literature. Maintenance ECT may reduce the frequency of breakthrough seizures in patients with seizure disorder that is inadequately responsive to antiepileptic medication regimes. Very high ECT seizure thresholds may be observed when many antiepileptic drugs are concurrently administered in high doses.

Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrest.

PubMed

Mégarbane, Bruno; Leprince, Pascal; Deye, Nicolas; Résière, Dabor; Guerrier, Gilles; Rettab, Samia; Théodore, Jonathan; Karyo, Souheil; Gandjbakhch, Iradj; Baud, Frédéric J

2007-05-01

To report the feasibility, complications, and outcomes of emergency extracorporeal life support (ECLS) in refractory cardiac arrests in medical intensive care unit (ICU). Prospective cohort study in the medical ICU in a university hospital in collaboration with the cardiosurgical team of a neighboring hospital. Seventeen patients (poisonings: 12/17) admitted over a 2-year period for cardiac arrest unresponsive to cardiopulmonary resuscitation (CPR) and advanced cardiac life support, without return of spontaneous circulation. ECLS femoral implantation under continuous cardiac massage, using a centrifugal pump connected to a hollow-fiber membrane oxygenator. Stable ECLS was achieved in 14 of 17 patients. Early complications included massive transfusions (n=8) and the need for surgical revision at the cannulation site for bleeding (n=1). Four patients (24%) survived at medical ICU discharge. Deaths resulted from multiorgan failure (n=8), thoracic bleeding(n=2), severe sepsis (n=2), and brain death (n=1). Massive hemorrhagic pulmonary edema during CPR (n=5) and major capillary leak syndrome (n=6) were observed. Three cardiotoxic-poisoned patients (18%, CPR duration: 30, 100, and 180 min) were alive at 1-year follow-up without sequelae. Two of these patients survived despite elevated plasma lactate concentrations before cannulation (39.0 and 20.0 mmol/l). ECLS was associated with a significantly lower ICU mortality rate than that expected from the Simplified Acute Physiology Score II (91.9%) and lower than the maximum Sequential Organ Failure Assessment score (>90%). Emergency ECLS is feasible in medical ICU and should be considered as a resuscitative tool for selected patients suffering from refractory cardiac arrest.

Refractory seizures due to a dural-based cavernoma masquerading as a meningioma.

PubMed

Zeng, Xianwei; Mahta, Ali; Kim, Ryan Y; Saad, Ali G; Kesari, Santosh

2012-04-01

A 37-year-old female presented with medically intractable complex partial seizures with secondary generalization. She was found to have a dural-based lesion with radiologic features of meningioma. A gross total resection was performed and pathology confirmed a diagnosis of cavernous angioma and she became seizure free after the surgical resection. Cavernous angioma should be considered in differential diagnosis of a dural-based lesion manifesting with refractory seizures.

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

PubMed

Reddy, Doodipala Samba; Golub, Victoria M

2016-04-01

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Is reoperation an option for patients with temporal lobe epilepsy after failure of surgery?

PubMed

Jung, Rebekka; Aull-Watschinger, Susanne; Moser, Doris; Czech, Thomas; Baumgartner, Christoph; Bonelli-Nauer, Sivlia; Pataraia, Ekaterina

2013-09-01

Epilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe. We systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies. Overall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60months, range 12-72); six patients (35.3%) were seizure free at least 12month before observation points (median duration 120.5months, range 35-155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI (p=0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery (p=0.116) and before reoperation (p=0.622) was not poorer compared to patients with congruent Video-EEG results. Reoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Establishment of a rhesus monkey model of chronic temporal lobe epilepsy using repetitive unilateral intra-amygdala kainic acid injections.

PubMed

Chi, Yajie; Wu, Bolin; Guan, Jianwei; Xiao, Kuntai; Lu, Ziming; Li, Xiao; Xu, Yuting; Xue, Shan; Xu, Qiang; Rao, Junhua; Guo, Yanwu

2017-09-01

Temporal lobe epilepsy (TLE) is a common type of acquired epilepsy refractory to medical treatment. As such, establishing animal models of this disease is critical to developing new and effective treatment modalities. Because of their small head size, rodents are not suitable for comprehensive electroencephalography (EEG) evaluation via scalp or subdural electrodes. Therefore, a larger primate model that closely recapitulates signs of TLE is needed; here we describe a rhesus monkey model resembling chronic TLE. Eight monkeys were divided into two groups: kainic acid (KA) group (n=6) and saline control group (n=2). Intra-amygdala KA injections were performed biweekly via an Ommaya device until obvious epileptiform discharges were recorded. Video-EEG recording was conducted intermittently throughout the experiment using both scalp and subdural electrodes. Brains were then analyzed for Nissl and glial fibrillary acid protein (GFAP) immunostaining. After 2-4 injections of KA (approximately 1.2-2.4mg, 0.12-0.24mg/kg), interictal epileptiform discharges (IEDs) were recorded in all KA-treated animals. Spontaneous recurrent seizures (SRSs) accompanied by symptoms mimicking temporal lobe absence (undetectable without EEG recording), but few mild motor signs, were recorded in 66.7% (four of six) KA-treated animals. Both IEDs and seizures indicated a primary epileptic zone in the right temporal region and contralateral discharges were later detected. Segmental pyramidal cell loss and gliosis were detected in the brain of a KA-treated monkey. Through a modified protocol of unilateral repetitive intra-amygdala KA injections, a rhesus monkey model with similar behavioral and brain electrical features as TLE was developed. Copyright © 2017 Elsevier Inc. All rights reserved.

Successful management of refractory cases of canine demodicosis with homeopathy medicine Graphitis.

PubMed

Ranjan, Rakesh; Dua, Kirti; Turkar, Sujata; Singh, Harkirat; Singla, L D

2014-12-01

Canine demodicosis is a refractory skin disease caused by excessive proliferation of mite Demodex canis. Despite availability of several treatment options, the disease poses a great challenge to clinicians for its long term management as some drugs may be ineffective or toxic. Present report describes successful treatment of two refractory cases of canine demodicosis using homeopathy medicine. After oral administration of Graphitis 200 C two drops once daily for 2 months, complete cure from the disease was observed. No adverse health effects of the medication were recorded during the treatment. Thus, it may be concluded that homeopathy medicine may be used safely for long-term management of canine demodicosis.

Use of Serum Infliximab Level Prior to Cyclosporine Salvage Therapy in Severe Ulcerative Colitis

PubMed Central

Bochenek, Ashley; Stein, Adam C.; Rubin, David T.

2014-01-01

Medical treatment options for severe, steroid refractory ulcerative colitis (UC) include infliximab (IFX) or cyclosporine (CSA), but general consensus has been that both agents should not be used together or even successively. We report a case of a 17-year-old male with severe UC refractory to IV steroids with successful sequential salvage therapy guided by serum IFX level. After primary lack of response to IFX, an undetectable serum IFX level and elevated IFX antibodies were followed by immediate transition to IV CSA. This case demonstrates the possibility of therapeutic drug monitoring of IFX levels when calculating the risk/benefit ratio for patients with steroid-refractory UC failing primary salvage therapy. PMID:26157857

Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.

PubMed

Park, Amy J; Paraiso, Marie Fidela R

2009-08-01

Refractory dyspareunia presents a challenging therapeutic dilemma. A woman with defecatory dysfunction and dyspareunia presented with stage 2 prolapse. She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis. The patient experienced increased dyspareunia and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management. She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months. Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Deodhar, Ajita; Thornton, Raymond H.

Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rathermore » than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.« less

Medical nutrition therapy is the essential cornerstone for effective treatment of "refractory" severe hypertriglyceridemia regardless of pharmaceutical treatment: Evidence from a Lipid Management Program.

PubMed

Rhodes, Katherine S; Weintraub, Martha; Marchlewicz, Elizabeth H; Rubenfire, Melvyn; Brook, Robert D

2015-01-01

Patients with refractory severe hypertriglyceridemia are at risk of pancreatitis and cardiovascular disease. The role of individualized nutrition therapy in these patients independent of pharmaceutical treatment has not been documented. To document the effect of nutrition intervention on severe hypertriglyceridemia regardless of medication status or prior nutrition counseling. Outcomes of new patients with triglycerides ≥ 500 mg/dL presenting to a Lipid Management Program over a 6-year period were tracked. Patients received comprehensive laboratory assessment, nutrition assessment, and initiation of an individualized diet intervention before seeing the lipidologist. Clinical and behavioral outcomes were recorded. In all, 168 patients (117 men; mean age, 49.03 ± 11.22 years; body mass index, 32.61 ± 5.85 kg/m(2); 110 (65.5%) on lipid-lowering medications) returned for assessment of nutrition intervention. Triglycerides were reduced from median (interquartile range) 961.5 (611.5-1785.3) to 493.0 (337-736.3) mg/dL (P < .0001 for log transformation of triglycerides). There was no difference in median percentage reduction in triglycerides after nutrition intervention between those not on lipid-lowering medication, on a fibric acid derivative, on other lipid-lowering medication, or on a combination of lipid-lowering medications (P = .376) in a median (interquartile range) of 5 (3-7) weeks. Effect was independent of prior nutrition counseling (P = .260). Reported percentage fat in the diet at second visit correlated with log-transformed triglycerides achieved, independent of initial triglycerides level (r = 0.290; P = .001). Individualized nutrition therapy results in changes in eating behavior and reductions in triglyceride levels in patients with refractory severe hypertriglyceridemia independent of lipid-lowering medication(s) and prior nutrition counseling. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Prospective Evaluation of Two iStent® Trabecular Stents, One iStent Supra® Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes.

PubMed

Myers, Jonathan S; Masood, Imran; Hornbeak, Dana M; Belda, Jose I; Auffarth, Gerd; Jünemann, Anselm; Giamporcaro, Jane Ellen; Martinez-de-la-Casa, Jose M; Ahmed, Iqbal Ike K; Voskanyan, Lilit; Katz, L Jay

2018-03-01

This study evaluates long-term outcomes of two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin in eyes with refractory open angle glaucoma (OAG). Prospective ongoing 5-year study of 80 eligible subjects (70 with 4-year follow-up) with OAG and IOP ≥ 18 mmHg after prior trabeculectomy and while taking 1-3 glaucoma medications. Subjects received two iStent ® trabecular micro-bypass stents, one iStent Supra ® suprachoroidal stent, and postoperative travoprost. Postoperative IOP was measured with medication and annually following medication washouts. Performance was measured by the proportion of eyes with ≥ 20% IOP reduction on one medication (the protocol-specified prostaglandin) versus preoperative medicated IOP (primary outcome); and the proportion of eyes with postoperative IOP ≤ 15 and ≤ 18 mmHg on one medication (secondary outcome). Additional clinical and safety data included medications, visual field, pachymetry, gonioscopy, adverse events, visual acuity, and slit-lamp and fundus examinations. Preoperatively, mean medicated IOP was 22.0 ± 3.1 mmHg on 1.2 ± 0.4 medications, and mean unmedicated IOP was 26.4 ± 2.4 mmHg. Postoperatively, among eyes without later cataract surgery, mean medicated IOP at all visits through 48 months was ≤ 13.7 mmHg (≥ 37% reduction), and annual unmedicated IOP was ≤ 18.4 mmHg (reductions of ≥ 30% vs. preoperative unmedicated IOP and ≥ 16% vs. preoperative medicated IOP). At all postoperative visits among eyes without additional surgery or medication, ≥ 91% of eyes had ≥ 20% IOP reduction on one medication versus preoperative medicated IOP. At month 48, 97 and 98% of eyes achieved IOP ≤ 15 and ≤ 18 mmHg, respectively, on one medication. Six eyes required additional medication, no eyes required additional glaucoma surgery, and safety measurements were favorable throughout follow-up. IOP control was achieved safely with two trabecular micro-bypass stents, one suprachoroidal stent, and postoperative prostaglandin. This microinvasive, ab interno approach introduces a possible new treatment option for refractory disease. NCT01456390. Glaukos Corporation.

Treatment-refractory anxiety; definition, risk factors, and treatment challenges

PubMed Central

Roy-Byrne, Peter

2015-01-01

A sizable proportion of psychiatric patients will seek clinical evaluation and treatment for anxiety symptoms reportedly refractory to treatment. This apparent lack of response is either due to “pseudo-resistance” (a failure to have received and adhered to a recognized and effective treatment or treatments for their condition) or to true “treatment resistance.” Pseudo-resistance can be due to clinician errors in selecting and delivering an appropriate treatment effectively, or to patient nonadherence to a course of treatment. True treatment resistance can be due to unrecognized exogenous anxiogenic factors (eg, caffeine overuse, sleep deprivation, use of alcohol or marijuana) or an incorrect diagnosis (eg, atypical bipolar illness, occult substance abuse, attention deficit-hyperactivity disorder). Once the above factors are eliminated, treatment should focus on combining effective medications and cognitive behavioral therapy, combining several medications (augmentation), or employing novel medications or psychotherapies not typically indicated as first-line evidence-based anxiety treatments. PMID:26246793

Treatment-refractory anxiety; definition, risk factors, and treatment challenges.

PubMed

Roy-Byrne, Peter

2015-06-01

A sizable proportion of psychiatric patients will seek clinical evaluation and treatment for anxiety symptoms reportedly refractory to treatment. This apparent lack of response is either due to "pseudo-resistance" (a failure to have received and adhered to a recognized and effective treatment or treatments for their condition) or to true "treatment resistance." Pseudo-resistance can be due to clinician errors in selecting and delivering an appropriate treatment effectively, or to patient nonadherence to a course of treatment. True treatment resistance can be due to unrecognized exogenous anxiogenic factors (eg, caffeine overuse, sleep deprivation, use of alcohol or marijuana) or an incorrect diagnosis (eg, atypical bipolar illness, occult substance abuse, attention deficit-hyperactivity disorder). Once the above factors are eliminated, treatment should focus on combining effective medications and cognitive behavioral therapy, combining several medications (augmentation), or employing novel medications or psychotherapies not typically indicated as first-line evidence-based anxiety treatments.

Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: Conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation.

PubMed

Siao, Fu-Yuan; Chiu, Chun-Chieh; Chiu, Chun-Wen; Chen, Ying-Chen; Chen, Yao-Li; Hsieh, Yung-Kun; Lee, Chien-Hui; Wu, Chang-Te; Chou, Chu-Chung; Yen, Hsu-Heng

2015-07-01

Refractory ventricular fibrillation, resistant to conventional cardiopulmonary resuscitation (CPR), is a life threatening rhythm encountered in the emergency department. Although previous reports suggest the use of extracorporeal CPR can improve the clinical outcomes in patients with prolonged cardiac arrest, the effectiveness of this novel strategy for refractory ventricular fibrillation is not known. We aimed to compare the clinical outcomes of patients with refractory ventricular fibrillation managed with conventional CPR or extracorporeal CPR in our institution. This is a retrospective chart review study from an emergency department in a tertiary referral medical center. We identified 209 patients presenting with cardiac arrest due to ventricular fibrillation between September 2011 and September 2013. Of these, 60 patients were enrolled with ventricular fibrillation refractory to resuscitation for more than 10 min. The clinical outcome of patients with ventricular fibrillation received either conventional CPR, including defibrillation, chest compression, and resuscitative medication (C-CPR, n = 40) or CPR plus extracorporeal CPR (E-CPR, n = 20) were compared. The overall survival rate was 35%, and 18.3% of patients were discharged with good neurological function. The mean duration of CPR was longer in the E-CPR group than in the C-CPR group (69.90 ± 49.6 min vs 34.3 ± 17.7 min, p = 0.0001). Patients receiving E-CPR had significantly higher rates of sustained return of spontaneous circulation (95.0% vs 47.5%, p = 0.0009), and good neurological function at discharge (40.0% vs 7.5%, p = 0.0067). The survival rate in the E-CPR group was higher (50% vs 27.5%, p = 0.1512) at discharge and (50% vs 20%, p = 0. 0998) at 1 year after discharge. The management of refractory ventricular fibrillation in the emergency department remains challenging, as evidenced by an overall survival rate of 35% in this study. Patients with refractory ventricular fibrillation receiving E-CPR had a trend toward higher survival rates and significantly improved neurological outcomes than those receiving C-CPR. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Supra-Tenon Capsule Implantation of the Ahmed Glaucoma Valve in Refractory Pediatric Glaucoma.

PubMed

Elhefney, Eman M; Al-Sharkawy, Hossam T; Kishk, Hanem M

2016-09-01

To evaluate the efficacy of supra-Tenon capsule implantation of an Ahmed glaucoma valve (AGV) as a measure to decrease the fibrotic potential of the Tenon capsule on bleb formation and its subsequent effect on intraocular pressure (IOP) control in children with refractory glaucoma. Mansoura Ophthalmic Centre, Faculty of Medicine, Mansoura University, Egypt. A prospective interventional study. Twenty-two eyes of 12 children with refractory glaucoma underwent supra-Tenon capsule implantation of AGV. Ophthalmic examinations under general anesthesia including measurement of the corneal diameter and the IOP with Perkin's tonometer were performed preoperatively, on the first postoperative day, the first postoperative week, weekly for the first month, 2-weekly for the following 3 months, and monthly for at least 18 months. Postoperative complications and the number of glaucoma medications used preoperatively and postoperatively were recorded. The paired Student t test was used to compare preoperative and postoperative data. There were 12 eyes (54.6%) with refractory congenital glaucoma, 7 eyes (31.8%) with refractory pseudophakic glaucoma, and 3 eyes (13.6%) with refractory aphakic glaucoma. Patients included 10 male (83.3%) and 2 female (16.7%) children with a mean age of 16.3±9.7 months. The mean follow-up duration was 24.1±4.3 months. There was a statistically significant difference between the mean preoperative IOP (30.7±2.88 mm Hg) and the mean postoperative IOP (16.1±3.60 mm Hg) (t=16.22 and P=0.000, with a mean decrease in the IOP by 47.6%). The difference between the mean number of antiglaucoma medications before surgery (1.86±0.4) and after surgery (1.0±0.9) was also statistically significant (t=4.31 and P=0.000). Total success was achieved in 18 eyes (81.9%). Postoperative complications included tube exposure and slippage (10%), hypotony (10%), and hyphema (5%). Supra-Tenon capsule implantation of the AGV was successful in controlling the IOP with few postoperative complications in the management of children with refractory glaucoma.

Long-term Outcomes of Ahmed Glaucoma Valve Implantation in Refractory Glaucoma at Farabi Eye Hospital, Tehran, Iran

PubMed Central

Zarei, Reza; Amini, Heidar; Daneshvar, Ramin; Nabi, Fahimeh Naderi; Moghimi, Sasan; Fakhraee, Ghasem; Eslami, Yadollah; Mohammadi, Masoud; Amini, Nima

2016-01-01

Purpose: To describe long-term outcomes and complications of Ahmed glaucoma valve (AGV) implantation in subjects with refractory glaucoma at Farabi Eye Hospital, Tehran, Iran. Materials and Methods: This retrospective cohort study evaluated patient records of all subjects with refractory glaucoma who had undergone AGV implantation up to January 2013. The main outcome measure was the surgical success rate. Complete success was defined as intraocular pressure (IOP) <22 mmHg, without anti-glaucoma medications or additional surgery. Qualified success was IOP <22 mmHg regardless of number of anti-glaucoma medications. In all cases, loss of vision (no light perception) was considered an independent indicator of failure. Data were also collected on intraoperative and postoperative complications. Results: Twenty-eight eyes were included in the study. With a mean follow-up of 48.2 ± 31.7 months (median: 40.50 months; range: 3–124 months), the IOP decreased from a mean preoperative value of 30.8 ± 5.6 mmHg to 20.0 ± 6.4 mmHg at last visit. The number of medications decreased from 3.7 ± 0.4 preoperatively to 2.5 ± 1.1 postoperatively. Cumulative qualified success was achieved in 69% of eyes. Mean time to failure according to qualified success criteria was 92.3 ± 9.4 months. Postoperative complications were recorded in 16 (57.1%) eyes. The most common complication was focal endothelial corneal decompensation at the site of tube-cornea touch. Conclusion: AGV implantation with adjunctive topical anti-glaucoma drops controlled IOP in approximately 70% of eyes with refractory glaucoma with a median of 40.5 months of follow-up. However, complication rates were higher. PMID:26957848

[Long-term outcomes of Ahmed glaucoma valve implantation for treating refractory glaucoma].

PubMed

Xu, Yumei; Hong, Tao; Li, Wanming

2015-02-10

To explore the efficacies and complications of Ahmed glaucoma valve implantation for treating refractory glaucoma. A retrospective study of case series was conducted for 24 patients (26 eyes) with refractory glaucoma from February 2001 to July 2008 at our hospital. Ahmed glaucoma valve implantation was performed. Pre- and post-operative best spectacle-corrected visual acuity (BSCVA), intraocular pressure (IOP), number of medications and complications were recorded and analyzed. The follow-up period was 58-159 months. The post-operative values of IOP were 13.02+/-6.79, 11.43+/-5.24 and 18.56+/-6.43 mmHg at 1 day, 1 month and the last follow-up respectively. There were significant difference when compared with pre-operative IOP (37.59+/-10.76 mmHg, P < 0.01). And 65.38% of eyes maintained or gained ≥ 1 line of BSCVA. But there was no significant difference with pre-operative BSCVA (P = 0.110). Twenty eyes required anti-glaucoma drugs after glaucoma valve implantation and the average number of medication was 1.72+/-0.98. There was significant difference with the pre-operative medication number 2.7 ± 0.7 (P = 0.001). The surgical success rate was 73.1%. And the causes of failure were endophthalmitis, corneal endothelial decompensation, persistent conjunctival wound non-healing, glaucoma valve exposure and loss of light perception.Early postoperative complications were ocular hypotony, shallow anterior chamber, hyphema, transient high IOP and tube occlusion. And long-term complications included encapsulated cyst formation, tube exposure, corneal endothelial decompensation and endophthalmitis. Ahmed glaucoma valve implantation is efficacious for refractory glaucoma.However, clinicians should pay attention to the prevention and treatment of complications.

Long-term Outcomes of Ahmed Glaucoma Valve Implantation in Refractory Glaucoma at Farabi Eye Hospital, Tehran, Iran.

PubMed

Zarei, Reza; Amini, Heidar; Daneshvar, Ramin; Nabi, Fahimeh Naderi; Moghimi, Sasan; Fakhraee, Ghasem; Eslami, Yadollah; Mohammadi, Masoud; Amini, Nima

2016-01-01

To describe long-term outcomes and complications of Ahmed glaucoma valve (AGV) implantation in subjects with refractory glaucoma at Farabi Eye Hospital, Tehran, Iran. This retrospective cohort study evaluated patient records of all subjects with refractory glaucoma who had undergone AGV implantation up to January 2013. The main outcome measure was the surgical success rate. Complete success was defined as intraocular pressure (IOP) <22 mmHg, without anti-glaucoma medications or additional surgery. Qualified success was IOP <22 mmHg regardless of number of anti-glaucoma medications. In all cases, loss of vision (no light perception) was considered an independent indicator of failure. Data were also collected on intraoperative and postoperative complications. Twenty-eight eyes were included in the study. With a mean follow-up of 48.2 ± 31.7 months (median: 40.50 months; range: 3-124 months), the IOP decreased from a mean preoperative value of 30.8 ± 5.6 mmHg to 20.0 ± 6.4 mmHg at last visit. The number of medications decreased from 3.7 ± 0.4 preoperatively to 2.5 ± 1.1 postoperatively. Cumulative qualified success was achieved in 69% of eyes. Mean time to failure according to qualified success criteria was 92.3 ± 9.4 months. Postoperative complications were recorded in 16 (57.1%) eyes. The most common complication was focal endothelial corneal decompensation at the site of tube-cornea touch. AGV implantation with adjunctive topical anti-glaucoma drops controlled IOP in approximately 70% of eyes with refractory glaucoma with a median of 40.5 months of follow-up. However, complication rates were higher.

Defining refractory migraine: results of the RHSIS Survey of American Headache Society members.

PubMed

Schulman, Elliott A; Peterlin, B Lee; Lake, Alvin E; Lipton, Richard B; Hanlon, Alexandra; Siegel, Sherry; Levin, Morris; Goadsby, Peter J; Markley, Herbert G

2009-04-01

To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. A 12-item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e-mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders-2 (86%), and that refractory forms of non-migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder-2. There was also general agreement by the responders that refractory forms of non-migraine headache disorders should be defined.

Antagonist molecules in the treatment of angina

PubMed Central

Gupta, Ashish K.; Winchester, David; Pepine, Carl J.

2017-01-01

Introduction Management of chronic angina has evolved dramatically in the last few decades with several options for pharmacotherapy outlined in various evidence-based guidelines. Areas covered There is a growing list of drugs that are currently being investigated for treatment of chronic angina. These also include several herbal medications, which are now being scientifically evaluated as potential alternative or even adjunctive therapy for angina. Gene- and cell-based therapies have opened yet another avenue for management of chronic refractory angina in ‘no-option’ patients who are not candidates for either percutaneous or surgical revascularization and are on optimal medical therapy. An extensive review of literature using PUBMED, Cochrane database, clinical trial databases of USA and European Union was done and summarized in this review. This review will attempt to discuss the traditional as well as novel therapeutic agents for angina. Expert opinion Several pharmacological and non-pharmacological therapeutic options are now available for treatment and management of chronic refractory angina. Renewed interest in traditional therapies and cell- and gene-based modalities with targeted drug delivery systems will open the doors for personalized therapy for patients with chronic refractory angina. PMID:24047238

Early tissue damage and microstructural reorganization predict disease severity in experimental epilepsy

PubMed Central

Janz, Philipp; Schwaderlapp, Niels; Heining, Katharina; Häussler, Ute; Korvink, Jan G; von Elverfeldt, Dominik; Hennig, Jürgen; Egert, Ulrich

2017-01-01

Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. DOI: http://dx.doi.org/10.7554/eLife.25742.001 PMID:28746029

Spread of epileptic activity in human brain

NASA Astrophysics Data System (ADS)

Milton, John

1997-03-01

For many patients with medically refractory epilepsy surgical resection of the site of seizure onset (epileptic focus) offers the best hope for cure. Determination of the nature of seizure propagation should lead to improved methods for locating the epileptic focus (and hence reduce patient morbidity) and possibly to new treatment modalities directed at blocking seizure spread. Theoretical studies of neural networks emphasize the role of traveling waves for the propagation of activity. However, the nature of seizure propagation in human brain remains poorly characterized. The spread of epileptic activity in patients undergoing presurgical evaluation for epilepsy surgery was measured by placing subdural grids of electrodes (interelectrode spacings of 3-10 mm) over the frontal and temporal lobes. The exact location of each electrode relative to the surface of the brain was determined using 3--D MRI imaging techniques. Thus it is possible to monitor the spread of epileptic activity in both space and time. The observations are discussed in light of models for seizure propagation.

Diverting Ileostomy for the Treatment of Severe, Refractory, Pediatric Inflammatory Bowel Disease.

PubMed

Maxwell, Elizabeth C; Dawany, Noor; Baldassano, Robert N; Mamula, Petar; Mattei, Peter; Albenberg, Lindsey; Kelsen, Judith R

2017-09-01

Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population. Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015. Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel. In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

PubMed

Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

2014-08-01

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

Prediction of treatment refractoriness in ulcerative colitis and Crohn's disease--do we have reliable markers?

PubMed

Gelbmann, C M

2000-05-01

Treatment refractoriness is a severe problem in the management of patients with ulcerative colitis and Crohn's disease. Despite some promising new therapeutic approaches, corticosteroids are still the preferential primary treatment for moderate to severe Crohn's disease and of severe ulcerative colitis. However, clinical response to corticosteroids varies, and many patients are resistant to such treatment. Since corticosteroids have frequent and even severe side effects, and toxicity increases with chronic steroid intake, factors predictive of response to such treatment would be very helpful for decisions on further management of these patients. At least in severe attacks of ulcerative colitis, the consensus seems to be that a high frequency of bowel movements as well as a high C-reactive protein and low serum albumin recorded after a few days of intensive medical treatment are important signs for early prediction of treatment failure in the majority of the patients. In Crohn's disease thus far, data on predictive factors are conflicting. No reliable marker with sufficient predictive value for treatment refractoriness could be identified. This might be due to the tremendous heterogeneity of Crohn's disease with many clinical phenotypes, which requires subgroup analysis with sufficient numbers of patients. Corticosteroids as well as other immunomodulating and immunosuppressive medications interfere with the immune system, which plays a central role in the mediation of intestinal inflammation. Treatment refractoriness might have its origin in specific immunological peculiarities eventually reflected in abnormal immunological, biochemical, and clinical parameters. Further exploration of those parameters to predict treatment refractoriness in patients with ulcerative colitis or Crohn's disease is of great clinical importance for safe and efficient management of patients.

Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

PubMed

Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

2013-11-01

The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

Early Use of the NMDA Receptor Antagonist Ketamine in Refractory and Superrefractory Status Epilepticus

PubMed Central

Zeiler, F. A.

2015-01-01

Refractory status epilepticus (RSE) and superrefractory status epilepticus (SRSE) pose a difficult clinical challenge. Multiple cerebral receptor and transporter changes occur with prolonged status epilepticus leading to pharmacoresistance patterns unfavorable for conventional antiepileptics. In particular, n-methyl-d-aspartate (NMDA) receptor upregulation leads to glutamate mediated excitotoxicity. Targeting these NMDA receptors may provide a novel approach to otherwise refractory seizures. Ketamine has been utilized in RSE. Recent systematic review indicates 56.5% and 63.5% cessation in seizures in adults and pediatrics, respectively. No complications were described. We should consider earlier implementation of ketamine or other NMDA receptor antagonists, for RSE. Prospective study of early implementation of ketamine should shed light on the role of such medications in RSE. PMID:25649724

Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

PubMed Central

Hashmi, Mubashira; Saleem, Feroza; Mustafa, Muhammad Shahid; Sheerani, Mughis; Ehtesham, Zeeshan; Siddiqui, Khurram

2010-01-01

Lafora disease is one of the rare, most fatal progressive myoclonic epilepsies reported. We present a case of a teenager with intractable seizures and progressive mental decline, diagnosed as Lafora body disease on axillary skin biopsy. He was admitted with status epilepticus with refractory myoclonic and generalised tonic clonic seizures. Despite on maximum doses of multiple antiepileptic drugs and infusions of propofol and midazolam, his seizures were refractory to all forms of medical therapy tried. Levetiracetam (LEV), a pyrrolidine derivative, was introduced; he showed a prompt response and was weaned off successfully from infusions of anticonvulsants and mechanical ventilation within 48 h of introduction of LEV, followed by an almost seizure-free status. PMID:22791845

Budget Impact Analysis to Estimate the Cost Dynamics of Treating Refractory Gastroesophageal Reflux Disease With Radiofrequency Energy: a Payer Perspective.

PubMed

Gregory, David; Scotti, Dennis J; Buck, Daniel; Triadafilopoulos, George

2016-05-01

A minimally invasive endoscopic treatment that utilizes radio-frequency energy (RFE) has received increased attention as an appropriate middle-ground approach in the treatment of refractory gastroesophageal reflux disease (GERD) and as an alternative to complicated and invasive surgical procedures. The objective of this study was to develop a longitudinal budget impact analysis from the payer perspective to estimate the direct medical costs of treatment for the refractory GERD patient population and to estimate the budgetary impact of further extending the RFE treatment option to other target populations. A retrospective analysis of claims designed to assess the longitudinal costs and budget impact on payer expenditures associated with managing and treating GERD surgically (Nissen fundoplication [NF]), endoscopically (RFE), or medically was performed. Both Medicare and commercially insured claims databases were interrogated for such population-level analyses. At current adoption rates (less than 1% of procedures), RFE demonstrated overall cost savings ranging from 7.3% to 50.5% in the 12-month time period following the index procedure (inclusive of procedure costs) when compared to medical management and fundoplication across the commercial and Medicare patient populations. Increasing the total number of RFE procedures to 2% of total cases performed generated per-member, per-month (PMPM) savings of $0.28 in the Medicare population and $0.37 in the commercially insured population. Further increases yielded higher PMPM savings. Adding to the clinical importance of RFE in filling the gap between medical and surgical management, this economic analysis demonstrates to payers that the adoption of RFE can create notable savings to their plans when compared to surgery or medical management.

Reasons for uncontrolled seizures in children: the impact of pseudointractability.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad

2012-11-01

We investigated the various possible reasons for uncontrolled seizures in patients under 18 years of age to determine the impact of pseudointractability. We also investigated the various forms of pseudointractability in children with uncontrolled seizures. In this cross-sectional retrospective chart review study, all patients under 18 years of age with their first seizure occurring at least 6 months prior to the referral date, taking at least one antiepileptic drug (AED), and having at least one seizure in the past 3 months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: poor adherence; wrong medication; wrong dose of the correct medication; diagnosis other than epilepsy; and finally, medically refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's Exact tests to determine potentially significant differences, and a P value less than 0.05 was considered significant. During the study period, 198 patients were referred to us due to uncontrolled seizures. Ninety patients (45%) were taking one AED, 55 (28%) were taking two AEDs, and 53 (27%) patients were taking more than two AEDs at the time of referral. Four percent of these patients did not have epilepsy. Forty-seven percent of the children with uncontrolled seizures had medically refractory epilepsy; 37% were taking the wrong AEDs; 10% were taking suboptimal doses of AEDs; and 2% had poor drug adherence. Uncontrolled seizures in children are a commonly encountered problem, particularly at epilepsy clinics. One should consider all possible reasons for these uncontrolled seizures, including non-epileptic seizures, pseudointractability, and medically refractory epilepsy. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2012 Elsevier Inc. All rights reserved.

Reasons for uncontrolled seizures in adults; the impact of pseudointractability.

PubMed

Asadi-Pooya, Ali A; Emami, Mehrdad; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Petramfar, Peyman; Yousefipour, Gholamali; Borhani-Haghighi, Afshin; Izadi, Sadegh; Rahimi-Jaberi, Abbas

2013-05-01

We investigated the various possible reasons for uncontrolled seizures in patients 18 years of age and older to determine the impact of pseudointractability. We also tried to investigate the various forms of pseudointractability. In this cross-sectional study, all patients 18 years of age and older with their first seizure occurring at least six months prior to the referral date, taking at least one antiepileptic drug (AED) and having at least one seizure in the past three months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: Poor compliance; Wrong medication (misclassification); Wrong dose of the correct medication; Diagnosis other than epilepsy; and finally, Medically-refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's exact tests, and a P value less than 0.05 was considered significant. 350 patients were referred to us due to uncontrolled seizures. One hundred ninety-one (55%) were male and 159 (45%) were female. Twelve percent of the patients had diagnoses other than epilepsy, 40% had indeed medically-refractory epilepsy; 29% were taking the wrong AEDs (misclassified epilepsy); 18% were taking suboptimal doses of AEDs; and 1% had poor drug compliance. The most common reason for uncontrolled seizures among patients with idiopathic generalized epilepsy was taking the wrong AED. However, among patients with focal epilepsy, true medically-refractory epilepsy was the most common reason. Uncontrolled seizures are a commonly encountered problem, especially at epilepsy clinics and one should consider all possible reasons for these uncontrolled seizures. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Temporal Lobe Epilepsy Surgery Failures: A Review

PubMed Central

Harroud, Adil; Bouthillier, Alain; Weil, Alexander G.; Nguyen, Dang Khoa

2012-01-01

Patients with temporal lobe epilepsy (TLE) are refractory to antiepileptic drugs in about 30% of cases. Surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20–30% of TLE patients. Several reasons have been identified to explain these surgical failures. This paper will address the five most common causes of TLE surgery failure (a) insufficient resection of epileptogenic mesial temporal structures, (b) relapse on the contralateral mesial temporal lobe, (c) lateral temporal neocortical epilepsy, (d) coexistence of mesial temporal sclerosis and a neocortical lesion (dual pathology); and (e) extratemporal lobe epilepsy mimicking TLE or temporal plus epilepsy. Persistence of epileptogenic mesial structures in the posterior temporal region and failure to distinguish mesial and lateral temporal epilepsy are possible causes of seizure persistence after TLE surgery. In cases of dual pathology, failure to identify a subtle mesial temporal sclerosis or regions of cortical microdysgenesis is a likely explanation for some surgical failures. Extratemporal epilepsy syndromes masquerading as or coexistent with TLE result in incomplete resection of the epileptogenic zone and seizure relapse after surgery. In particular, the insula may be an important cause of surgical failure in patients with TLE. PMID:22934162

Coding and decoding with adapting neurons: a population approach to the peri-stimulus time histogram.

PubMed

Naud, Richard; Gerstner, Wulfram

2012-01-01

The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a 'quasi-renewal equation' which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction.

Human cytomegalovirus and Epstein-Barr virus infection in inflammatory bowel disease: need for mucosal viral load measurement.

PubMed

Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto

2015-02-14

To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.

Antegrade continence enemas improve quality of life in patients with medically-refractory encopresis.

PubMed

Church, Joseph T; Simha, Sidd; Wild, Laurie C; Teitelbaum, Daniel H; Ehrlich, Peter F

2017-05-01

Fecal incontinence is a socially debilitating problem for many children. We hypothesized that in selected patients with medically-refractory encopresis, placement of an appendicostomy or cecostomy tube for administration of antegrade continence enemas (ACE) would improve quality of life (QOL). We reviewed all patients with encopresis who underwent appendicostomy or cecostomy placement from 2003 to 2014 at our institution. We contacted subjects' parents by phone and administered 3 surveys: a survey reflecting current stooling habits, a disease-specific QOL survey, and the PedsQL™ QOL survey. QOL surveys were completed twice by parents, once reflecting pre-operative QOL, then again reflecting current QOL. Pre-procedure and post-procedure scores were compared by paired t-test. Ten patients underwent appendicostomy/cecostomy for encopresis. Eight completed phone surveys. All procedures were performed laparoscopically. All patients experienced fecal soiling pre-operatively, whereas 5/8 surveyed patients (63%) noted complete resolution of soiling post-procedure (p<0.01). General and disease-specific QOL improved from pre-procedure to post-procedure in the following domains: social habits, physical activity, ability to spend the night elsewhere, feeling, and overall QOL (p<0.05). PedsQL™ scores improved significantly in physical functioning, social functioning, and overall functioning (p<0.05). Antegrade continence enemas significantly improve quality of life in patients with medically-refractory encopresis, likely related to resolution of soiling. 4. Copyright © 2017. Published by Elsevier Inc.

Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis.

PubMed

Odes, S; Vardi, H; Friger, M; Esser, D; Wolters, F; Moum, B; Waters, H; Elkjaer, M; Bernklev, T; Tsianos, E; O'Morain, C; Stockbrügger, R; Munkholm, P; Langholz, E

2010-04-01

Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort. Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.

Spatial variation in automated burst suppression detection in pharmacologically induced coma.

PubMed

An, Jingzhi; Jonnalagadda, Durga; Moura, Valdery; Purdon, Patrick L; Brown, Emery N; Westover, M Brandon

2015-01-01

Burst suppression is actively studied as a control signal to guide anesthetic dosing in patients undergoing medically induced coma. The ability to automatically identify periods of EEG suppression and compactly summarize the depth of coma using the burst suppression probability (BSP) is crucial to effective and safe monitoring and control of medical coma. Current literature however does not explicitly account for the potential variation in burst suppression parameters across different scalp locations. In this study we analyzed standard 19-channel EEG recordings from 8 patients with refractory status epilepticus who underwent pharmacologically induced burst suppression as medical treatment for refractory seizures. We found that although burst suppression is generally considered a global phenomenon, BSP obtained using a previously validated algorithm varies systematically across different channels. A global representation of information from individual channels is proposed that takes into account the burst suppression characteristics recorded at multiple electrodes. BSP computed from this representative burst suppression pattern may be more resilient to noise and a better representation of the brain state of patients. Multichannel data integration may enhance the reliability of estimates of the depth of medical coma.

Duloxetine in the treatment of burning mouth syndrome refractory to conventional treatment: A case report.

PubMed

Kim, Yeon-Dong; Lee, Ji-Hye; Shim, Jee-Hoon

2014-06-01

Patients with burning mouth syndrome (BMS) report burning sensation and pain involving the tongue and oral mucosa without any apparent medical or dental cause. The pathogenesis of this syndrome remains unclear and there is currently no standard treatment. BMS is, therefore, often misdiagnosed and its management is complex. This lack of clinical expertise may result in decreased health-related quality of life and increased psychological distress among patients with BMS. The present case report involves a 77-year-old female patient with BMS refractory to conventional treatment with nerve block and medication, who was successfully treated with duloxetine. Duloxetine may become a new therapeutic option in the management of BMS. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Recent trends and future directions for the medical treatment of ulcerative colitis.

PubMed

Naganuma, Makoto; Mizuno, Shinta; Nanki, Kosaku; Sugimoto, Shinya; Kanai, Takanori

2016-12-01

Recently, several medical treatments for ulcerative colitis (UC) have been developed, including 5-aminosalicylic acids (5-ASAs), corticosteroids, thiopurine, calcineurin inhibitors, and anti-tumor necrosis factor (TNF) α treatments. Treatment options including calcineurin inhibitors and anti-TNF treatment for refractory UC are discussed in this article. Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib. Budesonide foamwill be used as one treatment option in patients with distal colitis. Herbal medicine, such as Qing-Dai is also effective for active UC and may be useful for patients who are refractory to anti-TNFα treatments. In the near future, physicians will able to use many different treatments for UC patients. However, we should not forget 5-ASA and corticosteroids as the fundamental treatments for UC patients.

Update of Inpatient Treatment for Refractory Chronic Daily Headache.

PubMed

Lai, Tzu-Hsien; Wang, Shuu-Jiun

2016-01-01

Chronic daily headache (CDH) is a group of headache disorders, in which headaches occur daily or near-daily (>15 days per month) and last for more than 3 months. Important CDH subtypes include chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache. Other headaches with shorter durations (<4 h/day) are usually not included in CDH. Common comorbidities of CDH are medication overuse headache and various psychiatric disorders, such as depression and anxiety. Indications of inpatient treatment for CDH patients include poor responses to outpatient management, need for detoxification for overuse of specific medications (particularly opioids and barbiturates), and severe psychiatric comorbidities. Inpatient treatment usually involves stopping acute pain, preventing future attacks, and detoxifying medication overuse if present. Multidisciplinary integrated care that includes medical staff from different disciplines (e.g., psychiatry, clinical psychology, and physical therapy) has been recommended. The outcomes of inpatient treatment are satisfactory in terms of decreasing headache intensity or frequency, withdrawal from medication overuse, reducing disability, and improving life quality, although long-term relapse is not uncommon. In conclusion, inpatient treatment may be useful for select patients with refractory CDH and should be incorporated in a holistic headache care program.

Treatment of Refractory Idiopathic Supraorbital Neuralgia Using Percutaneous Pulsed Radiofrequency.

PubMed

Luo, Fang; Lu, Jingjing; Ji, Nan

2018-02-26

No ideal therapeutic method currently exists for refractory idiopathic supraorbital neuralgia patients who do not respond to conservative therapy, including medications and nerve blocks. Pulsed radiofrequency is a neuromodulation technique that does not produce sequelae of nerve damage after treatment. However, the efficacy of percutaneous pulsed radiofrequency for the treatment of refractory idiopathic supraorbital neuralgia is still not clear. The purpose of our study was to evaluate the efficacy and safety of pulsed radiofrequency treatment of the supraorbital nerve for refractory supraorbital neuralgia patients. We prospectively investigated the long-term effects of ultrasound-guided percutaneous pulsed radiofrequency in the treatment of 22 refractory idiopathic supraorbital neuralgia patients. A reduction in the verbal pain numeric rating scale score of more than 50% was used as the standard of effectiveness. The effectiveness rates at different time points within 2 years were calculated. After a single pulsed radiofrequency treatment, the effectiveness rate at 1 and 3 months was 77%, and the rates at 6 months, 1 year, and 2 years were 73%, 64%, and 50%, respectively. Except for a small portion of patients (23%) who experienced mild upper eyelid ecchymosis that gradually disappeared after approximately 2 weeks, no obvious complications were observed. In conclusion, the results of our study demonstrate that for patients with refractory idiopathic supraorbital neuralgia, percutaneous pulsed radiofrequency may be an effective and safe treatment choice. © 2018 World Institute of Pain.

Review and update of the Hong Kong Epilepsy Guideline on status epilepticus.

PubMed

Fung, E Lw; Fung, B Bh

2017-02-01

Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam. Valproate and levetiracetam have also emerged as possible alternatives to phenytoin in established status epilepticus. The potential role of lacosamide in this stage of status epilepticus remains to be defined. The ongoing Established Status Epilepticus Treatment Trial may help to determine the most effective treatment for benzodiazepine-resistant status epilepticus. Management of refractory status epilepticus and super-refractory status epilepticus remains mostly non-evidence-based. Increasing recognition of a possible autoimmune aetiology has led to the use of immune-modulation in super-refractory status epilepticus. Ketamine is also increasingly used in this challenging condition. There are also reports of potential use of a ketogenic diet and magnesium.

Surgical management of canine refractory retrobulbar abscesses: six cases.

PubMed

Tremolada, G; Milovancev, M; Culp, W T N; Bleedorn, J A

2015-11-01

To report the clinical presentation, surgical treatment and outcomes of dogs with retrobulbar abscesses refractory to intra-oral lancing and antibiotics. Medical records from January 2006 through September 2014 were reviewed and dogs with retrobulbar abscesses failing treatment with antibiotics and intra-oral lancing were included. Clinicopathologic, imaging and surgical details were extracted from the medical records. Referring veterinarians and owners were interviewed via telephone for follow-up data. A total of six dogs were included in the study. The most common clinical signs were pain upon opening of the mouth, exophthalmos and prolapsed nictitans. Computed tomography was performed in five dogs, ultrasound in four and magnetic resonance imaging in one. Imaging identified an abscess in all dogs, with a suspected foreign body in four dogs. Surgical approach was a modified lateral orbitotomy in five dogs. No foreign body was identified during surgery in all dog. All dogs surviving to discharge did not have recurrence of clinical signs (follow-up time range: 27 to 95 months). Dogs with retrobulbar abscesses refractory to standard therapy can experience long-term resolution of clinical signs with surgical treatment, most commonly via a modified lateral orbitotomy. © 2015 British Small Animal Veterinary Association.

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study.

PubMed

Van Paesschen, W; King, M D; Duncan, J S; Connelly, A

2001-07-01

To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe

Ketogenic diet treatment for pediatric super-refractory status epilepticus.

PubMed

Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

2016-10-01

We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

PubMed

Kellermann, Tanja S; Wagner, Janelle L; Smith, Gigi; Karia, Samir; Eskandari, Ramin

2016-11-01

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians. Surgical treatment of epilepsy can be critical to avoid negative outcomes in functional, cognitive, and behavioral health status. Furthermore, it is often the only method to achieve seizure freedom in refractory epilepsy. Although a large literature base can be found for adults with refractory epilepsy undergoing surgical treatment, less is known about how surgical management affects outcomes in children with epilepsy. The purpose of the review was fourfold: (1) to evaluate the available literature regarding presurgical assessment and postsurgical outcomes in children with medically refractory epilepsy, (2) to identify gaps in our knowledge of surgical treatment and its outcomes in children with epilepsy, (3) to pose questions for further research, and (4) to advocate for a more unified presurgical evaluation protocol including earlier referral for surgical candidacy of pediatric patients with refractory epilepsy. Despite its effectiveness, epilepsy surgery remains an underutilized but evidence-based approach that could lead to positive short- and long-term outcomes for children with refractory epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

A stochastic-field description of finite-size spiking neural networks

PubMed Central

Longtin, André

2017-01-01

Neural network dynamics are governed by the interaction of spiking neurons. Stochastic aspects of single-neuron dynamics propagate up to the network level and shape the dynamical and informational properties of the population. Mean-field models of population activity disregard the finite-size stochastic fluctuations of network dynamics and thus offer a deterministic description of the system. Here, we derive a stochastic partial differential equation (SPDE) describing the temporal evolution of the finite-size refractory density, which represents the proportion of neurons in a given refractory state at any given time. The population activity—the density of active neurons per unit time—is easily extracted from this refractory density. The SPDE includes finite-size effects through a two-dimensional Gaussian white noise that acts both in time and along the refractory dimension. For an infinite number of neurons the standard mean-field theory is recovered. A discretization of the SPDE along its characteristic curves allows direct simulations of the activity of large but finite spiking networks; this constitutes the main advantage of our approach. Linearizing the SPDE with respect to the deterministic asynchronous state allows the theoretical investigation of finite-size activity fluctuations. In particular, analytical expressions for the power spectrum and autocorrelation of activity fluctuations are obtained. Moreover, our approach can be adapted to incorporate multiple interacting populations and quasi-renewal single-neuron dynamics. PMID:28787447

Epidural blood patch for refractory low CSF pressure headache: a pilot study.

PubMed

Madsen, Søren Aalbæk; Fomsgaard, Jonna Storm; Jensen, Rigmor

2011-08-01

Once believed an exceedingly rare disorder, recent evidence suggests that low cerebrospinal fluid (CSF) pressure headache has to be considered an important cause of new daily persistent headaches, particularly among young and middle-aged individuals. Treatment of low CSF pressure headache consists of non-invasive/conservative measures and invasive measures with epidural blood patch providing the cornerstone of the invasive measures. In the present pilot study we therefore aimed to evaluate the treatment efficacy of epidural blood patch (EBP) in treatment-refractory low-pressure headache. Our primary effect parameter was total headache burden defined as area under the curve (AUC: intensity × duration) and as secondary effect parameters we identified: intensity (VAS 0-10), frequency (days per month), duration in hours (total hours/month) and also medication days (days on medication/month). In our primary effect parameter we found a significant reduction in AUC with more than 25% and this is considered to be clinically relevant. We found also a significant and relevant reduction at -22% in intensity. A trend towards reduction in duration was seen. We found no statistically significant reduction in frequency. An increase in days with use of medication was found. Increased awareness of low CSF pressure headache is emphasized and a controlled larger randomized study is needed to confirm the results. However the present results, allows us to conclude that EBP in treatment-refractory low CSF pressure headache can be considered as a treatment option.

Vagus nerve stimulation therapy in partial epilepsy: a review.

PubMed

Panebianco, Mariangela; Zavanone, Chiara; Dupont, Sophie; Restivo, Domenico A; Pavone, Antonino

2016-09-01

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

Coding and Decoding with Adapting Neurons: A Population Approach to the Peri-Stimulus Time Histogram

PubMed Central

Naud, Richard; Gerstner, Wulfram

2012-01-01

The response of a neuron to a time-dependent stimulus, as measured in a Peri-Stimulus-Time-Histogram (PSTH), exhibits an intricate temporal structure that reflects potential temporal coding principles. Here we analyze the encoding and decoding of PSTHs for spiking neurons with arbitrary refractoriness and adaptation. As a modeling framework, we use the spike response model, also known as the generalized linear neuron model. Because of refractoriness, the effect of the most recent spike on the spiking probability a few milliseconds later is very strong. The influence of the last spike needs therefore to be described with high precision, while the rest of the neuronal spiking history merely introduces an average self-inhibition or adaptation that depends on the expected number of past spikes but not on the exact spike timings. Based on these insights, we derive a ‘quasi-renewal equation’ which is shown to yield an excellent description of the firing rate of adapting neurons. We explore the domain of validity of the quasi-renewal equation and compare it with other rate equations for populations of spiking neurons. The problem of decoding the stimulus from the population response (or PSTH) is addressed analogously. We find that for small levels of activity and weak adaptation, a simple accumulator of the past activity is sufficient to decode the original input, but when refractory effects become large decoding becomes a non-linear function of the past activity. The results presented here can be applied to the mean-field analysis of coupled neuron networks, but also to arbitrary point processes with negative self-interaction. PMID:23055914

Vedolizumab as a rescue therapy for patients with medically refractory Crohn's disease.

PubMed

Crowell, K T; Tinsley, A; Williams, E D; Coates, M D; Bobb, A; Koltun, W A; Messaris, E

2018-04-19

Vedolizumab, a monoclonal antibody resulting in gut-selective anti-inflammatory activity, was approved by the US Food and Drug Administration in 2014 for use in patients with Crohn's disease (CD). The aim of this study was to investigate the efficacy of vedolizumab as a rescue therapy when other medical therapies have failed. A retrospective review was performed on consecutive patients with CD receiving vedolizumab at the Penn State Hershey IBD Center between May 2014 and March 2016. These patients were unresponsive or intolerant to tumour necrosis factor (TNF) antagonist therapy, and previously would have been candidates for surgery. Outcomes included surgical intervention, clinical response and endoscopic improvement. A total of 48 patients with medically refractory CD receiving vedolizumab were included. The median length of follow-up was 69 weeks (range 15-113 weeks). A majority (81%) of patients previously failed at least two TNF antagonists, and 77% had prior surgery for CD. Surgical intervention was required in 21 (44%) patients and 13 (27%) patients required intra-abdominal operations. At the conclusion of the study, 23 (48%) patients reported continued improvement of symptoms, and 22 of 37 (59%) patients undergoing endoscopy showed improvement. Patients with the inflammatory CD phenotype were more likely to improve clinically and avoid surgery. Vedolizumab alone or in combination with immunomodulators or steroids may be used as a rescue therapy in patients with medically refractory CD and may decrease the rate of surgical intervention. Patients with the inflammatory CD phenotype had the best clinical response and decreased need for surgery, suggesting that vedolizumab is most effective in the inflammatory phenotype. Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.

Treatment of Patellar Tendinopathy Refractory to Surgical Management Using Percutaneous Ultrasonic Tenotomy and Platelet-Rich Plasma Injection: A Case Presentation.

PubMed

Nanos, Katherine N; Malanga, Gerard A

2015-12-01

Chronic proximal patellar tendinopathy is a common condition in sports medicine that may be refractory to nonoperative treatments, including activity modification, medications, and comprehensive rehabilitation. Percutaneous ultrasonic tenotomy is a recently developed technique designed to cut and debride tendinopathic tissue, thus promoting pain relief and functional recovery. We present a case of a collegiate athlete with chronic proximal patellar tendinopathy who was effectively treated with percutaneous ultrasonic tenotomy after not responding to extensive nonoperative treatment, surgical debridement, and platelet-rich plasma injections. Percutaneous ultrasonic tenotomy can be considered as a treatment option in patients presenting with refractory proximal patellar tendinopathy, including those who do not respond to previous operative intervention. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Reversible bull's-eye maculopathy associated with intravitreal fomivirsen therapy for cytomegalovirus retinitis.

PubMed

Stone, T W; Jaffe, G J

2000-08-01

To report two cases in which a bull's eye maculopathy developed after intravitreal injection of fomivirsen. Case reports. A 50-year-old man with acquired immunodeficiency syndrome (AIDS) and refractory cytomegalovirus retinitis developed bull's-eye pigmentary changes in the macula of the right eye after initiating therapy with fomivirsen (Vitravene; CIBA Vision, Atlanta, Georgia) intravitreal injections. These pigmentary changes resolved upon cessation of treatment. A 36-year-old man with AIDS and refractory bilateral cytomegalovirus retinitis developed bull's-eye pigmentary changes in both eyes during bilateral intravitreal treatment with fomivirsen. Vision was not affected. These changes resolved after treatment with fomivirsen was stopped. Fomivirsen, a new medication for the treatment of refractory cytomegalovirus retinitis, may cause a bull's-eye maculopathy in some patients. The bull's-eye maculopathy is reversible and does not appear to affect vision.

Morphometric MRI features are associated with surgical outcome in mesial temporal lobe epilepsy with hippocampal sclerosis.

PubMed

Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Sandim, Gabriel Barbosa; Assunção Leme, Idaiane Batista; Carrete, Henrique; Centeno, Ricardo Silva; Sato, João Ricardo; Yacubian, Elza Márcia Targas

2017-05-01

Corticoamygdalohippocampectomy (CAH) improves seizure control, quality of life, and decreases mortality for refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). One-third of patients continue having seizures, and it is pivotal to determine structural abnormalities that might influence the postoperative outcome. Studies indicate that nonhippocampal regions may play a role in the epileptogenic network in MTLE-HS and could generate seizures postoperatively. The aim of this study is to analyze areas of atrophy, not always detected on routine MRI, comparing patients who became seizure free (SF) with those non seizure free (NSF) after CAH, in an attempt to establish possible predictors of surgical outcome. 105 patients with refractory MTLE-HS submitted to CAH (59 left MTLE; 46 males) and 47 controls were enrolled. FreeSurfer was performed for cortical thickness and volume estimation comparing patients to controls and SF versus NSF patients. The final sample after post processing procedures resulted in 99 patients. Cortical thickness analyses showed reductions in left insula in NSF patients compared to those SF. Significant volume reductions in SF patients were present in bilateral thalami, hippocampi and pars opercularis, left parahippocampal gyrus and right temporal pole. In NSF patients reductions were present bilaterally in thalami, hippocampi, entorhinal cortices, superior frontal and supramarginal gyri; on the left: superior and middle temporal gyri, temporal pole, parahippocampal gyrus, pars opercularis and middle frontal gyrus; and on the right: precentral, superior, middle and inferior temporal gyri. Comparison between SF and NSF patients showed ipsilateral gray matter reductions in the right entorhinal cortex (p=0.003) and contralateral parahippocampal gyrus (p=0.05) in right MTLE-HS. Patients NSF had a longer duration of epilepsy than those SF (p=0.028). NSF patients exhibited more extensive areas of atrophy than SF ones. As entorhinal cortex and parahippocampal gyrus are reduced in NSF patients compared to those SF these structures might be implicated in the network responsible for the maintenance of postoperative seizures. Duration of epilepsy is a predictor of seizure outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2015-12-03

Nearly 30% of patients with epilepsy continue to have seizures in spite of using several antiepileptic drug (AED) regimens. Such patients are regarded as having refractory, or uncontrolled, epilepsy. No definition of uncontrolled, or medically refractory, epilepsy has been universally accepted, but for the purposes of this review, we will consider seizures as drug resistant if they have failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age, which, in turn, may improve the intellectual and social status of children. Many types of surgery are available for treatment of refractory epilepsy; one such procedure is known as subpial transection. To determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (29 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; May 2015, Issue 5) and MEDLINE (1946 to 29 June 2015). We imposed no language restrictions. We considered all randomised and quasi-randomised parallel-group studies, whether blinded or non-blinded. Two review authors (BK and SR) independently screened trials identified by the search. The same two review authors planned to independently assess the methodological quality of studies. When studies were identified for inclusion, one review author would have extracted the data, and the other would have verified the data. We found no relevant studies. We found no evidence to support or refute use of subpial transection surgery for patients with medically refractory epilepsy. Well-designed randomised controlled trials are needed to guide clinical practice.

Extracorporeal shockwave myocardial revascularization improves clinical symptoms and left ventricular function in patients with refractory angina.

PubMed

Zuozienė, Gitana; Laucevičius, Aleksandras; Leibowitz, David

2012-01-01

Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Patients with Canadian Cardiovascular Society (CCS) class III-IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Twenty patients (four women, 16 men; mean age 64 years, range 45-83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

A prospective comparative study on neovascular glaucoma and non-neovascular refractory glaucoma following Ahmed glaucoma valve implantation.

PubMed

Li, Zheng; Zhou, Minwen; Wang, Wei; Huang, Wenbin; Chen, Shida; Li, Xingyi; Gao, Xinbo; Zhang, Xiulan

2014-01-01

Neovascular glaucoma is a refractory disease, and difficult to manage. The aim of this study was to evaluate the clinical outcomes of Ahmed glaucoma valve implantation (AGVI) in neovascular glaucoma (NVG) and non-NVG patients. This prospective, non-randomized study included 55 eyes of 55 patients with refractory glaucoma; 27 had NVG (NVG group) and 28 had non-NVG (non-NVG group). All of the patients underwent AGVI. The NVG group was adjunctively injected with intravitreal ranibizumab/bevacizumab (IVR/IVB) before AGVI. Intraocular pressure (IOP) was the primary outcome measure in this study. Surgical success rate, number of antiglaucoma medications used, best corrected visual acuity (BCVA), and postoperative complications were analyzed between the groups. All of the patients completed the study (follow-up of 12 months). Kaplan-Meier survival curve analysis indicated that the qualified success rates in the NVG and non-NVG groups at 12 months were 70.5% and 92.9%, respectively; this difference was significant (P = 0.036). The complete success rates in the NVG and non-NVG groups at 12 months were 66.7% and 89.3%, respectively (P = 0.049). Compared with preoperative examinations, the postoperative mean IOP and use of medications were significantly lower at all follow-up time points in both groups (all P < 0.05). There were significant differences in BCVA between the two groups at the 12-month follow-up (χ(2) = 9.86, P = 0.020). Cox proportional hazards regression showed NVG as a risk factor for surgical failure (RR = 15.08, P = 0.033). Postoperative complications were similar between the two groups. AGVI is a safe and effective procedure in refractory glaucoma, but the success rate of surgery was related to the type of refractory glaucoma. The complete and qualified success rates of NVG patient adjunctive anti-vascular endothelial growth factor treatment are still lower than those of non-NVG patients.

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach.

PubMed

Korsten, Peter; Strohmayer, Katharina; Baughman, Robert P; Sweiss, Nadera J

2016-03-01

Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach.

Illness identity in young adults with refractory epilepsy.

PubMed

Luyckx, Koen; Oris, Leen; Raymaekers, Koen; Rassart, Jessica; Moons, Philip; Verdyck, Ludo; Mijnster, Teus; Mark, Ruth E

2018-03-01

Refractory epilepsy is an intrusive condition with important implications for daily functioning in emerging and young adulthood. The present study examined the degree to which refractory epilepsy is integrated in one's identity, and examined how such a sense of illness identity was related to health-related quality of life (HRQOL). A total of 121 18- to 40-year-old patients with refractory epilepsy (56.2% women) completed self-report questionnaires assessing the four illness identity states of acceptance, enrichment, engulfment, and rejection (Illness Identity Questionnaire (IIQ)); HRQOL (Quality of Life in Epilepsy Inventory - 31); and seizure frequency and severity (Liverpool Seizure Severity Scale (LSSS)). Illness identity scores were compared with a sample of 191 patients with a nonneurological chronic disease (congenital heart disease). Hierarchical regression analyses were conducted to assess the predictive value of illness identity for HRQOL when simultaneously controlling for demographic and clinical features. Patients with refractory epilepsy scored higher on rejection and engulfment and lower on acceptance when compared with patients with congenital heart disease. Further, seizure severity and number of medication side-effects were positively related to engulfment and negatively to acceptance. Finally, when simultaneously controlling for various demographic and clinical variables, illness identity significantly predicted HRQOL (with engulfment being the strongest and most consistent predictor). The extent to which patients with refractory epilepsy succeed in integrating their illness into their identity may have important implications for HRQOL. Clinicians should be especially attentive for signs that patients feel engulfed by their epilepsy. Copyright © 2018 Elsevier Inc. All rights reserved.

[Epilepsy, cognition and ketogenic diet].

PubMed

Garcia-Penas, J J

2018-03-01

Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

Stimulation of the bilateral anterior nuclei of the thalamus in the treatment of refractory epilepsy: two cases of subcortical band heterotopia.

PubMed

Franco, Ana; Pimentel, José; Campos, Alexandre Rainha; Morgado, Carlos; Pinelo, Sara; Ferreira, António Gonçalves; Bentes, Carla

2016-12-01

Subcortical band heterotopia is a neuronal migration disorder that may cause refractory epilepsy. In these patients, resective surgery has yielded inadequate results. Deep brain stimulation of the anterior nuclei of the thalamus has been used for the treatment of refractory epilepsy with good results. We describe the first two patients with subcortical band heterotopia who were submitted to deep brain stimulation of the anterior nuclei of the thalamus, with evaluation of seizure outcome after 12 and 18 months of follow-up. At these times, both showed a >50% decrease in seizure frequency and an increase in seizure freedom. Both patients had a depressive syndrome after surgery that responded fully to anti-depressive medication in one patient and partly in the other. In both, deep brain stimulation of the anterior nuclei of the thalamus was associated with good seizure outcome. This procedure can therefore be considered in the treatment of patients with subcortical band heterotopia and refractory epilepsy. Depression may be a transient adverse event of the surgery or stimulation, however, its aetiology is probably multifactorial.

Genomic Testing and Resulting Medical Decisions

ClinicalTrials.gov

2017-10-03

Cancer of Unknown Origin; Cancer Refractory; Cancer of Stomach; Cancer Head Neck; Cancer of Skin; Cancer, Lung; Cancer Colorectal; Cancer of Esophagus; Cancer, Bladder; Cancer, Uterus; Cancer Cervix; Cancer Liver; Cancer, Kidney; Cancer, Breast; Hematologic Neoplasms

Relationship between neuronal network architecture and naming performance in temporal lobe epilepsy: A connectome based approach using machine learning.

PubMed

Munsell, B C; Wu, G; Fridriksson, J; Thayer, K; Mofrad, N; Desisto, N; Shen, D; Bonilha, L

2017-09-09

Impaired confrontation naming is a common symptom of temporal lobe epilepsy (TLE). The neurobiological mechanisms underlying this impairment are poorly understood but may indicate a structural disorganization of broadly distributed neuronal networks that support naming ability. Importantly, naming is frequently impaired in other neurological disorders and by contrasting the neuronal structures supporting naming in TLE with other diseases, it will become possible to elucidate the common systems supporting naming. We aimed to evaluate the neuronal networks that support naming in TLE by using a machine learning algorithm intended to predict naming performance in subjects with medication refractory TLE using only the structural brain connectome reconstructed from diffusion tensor imaging. A connectome-based prediction framework was developed using network properties from anatomically defined brain regions across the entire brain, which were used in a multi-task machine learning algorithm followed by support vector regression. Nodal eigenvector centrality, a measure of regional network integration, predicted approximately 60% of the variance in naming. The nodes with the highest regression weight were bilaterally distributed among perilimbic sub-networks involving mainly the medial and lateral temporal lobe regions. In the context of emerging evidence regarding the role of large structural networks that support language processing, our results suggest intact naming relies on the integration of sub-networks, as opposed to being dependent on isolated brain areas. In the case of TLE, these sub-networks may be disproportionately indicative naming processes that are dependent semantic integration from memory and lexical retrieval, as opposed to multi-modal perception or motor speech production. Copyright © 2017. Published by Elsevier Inc.

Contributions to singing ability by the posterior portion of the superior temporal gyrus of the non-language-dominant hemisphere: First evidence from subdural cortical stimulation, Wada testing, and fMRI

PubMed Central

Suarez, Ralph O.; Golby, Alexandra; Whalen, Stephen; Sato, Susumu; Theodore, William H.; Kufta, Conrad V.; Devinsky, Orrin; Balish, Marshall; Bromfield, Edward B.

2009-01-01

INTRODUCTION Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electrocortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity. METHODS We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional MRI. Functional organization of singing ability compared to language ability was determined based on four regions-ofinterest: left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG). RESULTS In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. FMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the regions-of-interest. CONCLUSION Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients. PMID:19570530

Surgical management of Crohn's disease.

PubMed

Lu, Kim C; Hunt, Steven R

2013-02-01

Although medical management can control symptoms in a recurring incurable disease, such as Crohn's disease, surgical management is reserved for disease complications or those problems refractory to medical management. In this article, we cover general principles for the surgical management of Crohn's disease, ranging from skin tags, abscesses, fistulae, and stenoses to small bowel and extraintestinal disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Seizures and Teens: Surgery for Seizures--What's It All About?

ERIC Educational Resources Information Center

Duchowny, Michael S.; Dean, Patricia

2006-01-01

Nearly 1 out of 2 children and teens with seizures may need to take medications throughout their lives. At least 25% will develop a condition called refractory epilepsy--meaning that their seizures do not respond to medical therapy. For these children and teens, non-drug therapies such as brain surgery are available that may offer a chance to…

The cost-effectiveness of sacral nerve stimulation (SNS) for the treatment of idiopathic medically refractory overactive bladder (wet) in the UK.

PubMed

Autiero, Silke Walleser; Hallas, Natalie; Betts, Christopher D; Ockrim, Jeremy L

2015-12-01

To estimate the long-term cost-effectiveness of specialised treatment options for medically refractory idiopathic overactive bladder (OAB) wet. The cost-effectiveness of competing treatment options for patients with medically refractory idiopathic OAB wet was estimated from the perspective of the National Health Service in the UK. We compared sacral nerve stimulation (SNS) with percutaneous nerve evaluation (PNE) or tined-lead evaluation (TLE) with optimal medical therapy (OMT), botulinum toxin type A (BoNT-A) injections, and percutaneous tibial nerve stimulation (PTNS). We used a Markov model with a 10-year time horizon for all treatment options with the exception of PTNS, which has a time horizon of 5 years. Costs and effects (measured as quality-adjusted life years) were calculated to derive incremental cost-effectiveness ratios (ICERs). Direct medical resources included are: device and drug acquisition costs, pre-procedure and procedure costs, and the cost of managing adverse events. Deterministic sensitivity analyses were performed to test robustness of results. At 5 years, SNS (PNE or TLE) was more effective and less costly than PTNS. Compared with OMT at 10 years, SNS (PNE or TLE) was more costly and more effective, and compared with BoNT-A, SNS PNE was less costly and more effective, and SNS TLE was more costly and more effective. Decreasing the BoNT-A dose from 150 to 100 IU marginally increased the 10 year ICERs for SNS TLE and PNE (SNS PNE was no longer dominant). However, both SNS options remained cost-effective. In the management of patients with idiopathic OAB wet, the results of this cost-utility analysis favours SNS (PNE or TLE) over PTNS or OMT, and the most efficient treatment strategy is SNS PNE over BoNT-A over a 10-year period. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Isotopic Dichotomy among Meteorites and Its Bearing on the Protoplanetary Disk

NASA Astrophysics Data System (ADS)

Scott, Edward R. D.; Krot, Alexander N.; Sanders, Ian S.

2018-02-01

Whole rock Δ17O and nucleosynthetic isotopic variations for chromium, titanium, nickel, and molybdenum in meteorites define two isotopically distinct populations: carbonaceous chondrites (CCs) and some achondrites, pallasites, and irons in one and all other chondrites and differentiated meteorites in the other. Since differentiated bodies accreted 1–3 Myr before the chondrites, the isotopic dichotomy cannot be attributed to temporal variations in the disk. Instead, the two populations were most likely separated in space, plausibly by proto-Jupiter. Formation of CCs outside Jupiter could account for their characteristic chemical and isotopic composition. The abundance of refractory inclusions in CCs can be explained if they were ejected by disk winds from near the Sun to the disk periphery where they spiraled inward due to gas drag. Once proto-Jupiter reached 10–20 M ⊕, its external pressure bump could have prevented millimeter- and centimeter-sized particles from reaching the inner disk. This scenario would account for the enrichment in CCs of refractory inclusions, refractory elements, and water. Chondrules in CCs show wide ranges in Δ17O as they formed in the presence of abundant 16O-rich refractory grains and 16O-poor ice particles. Chondrules in other chondrites (ordinary, E, R, and K groups) show relatively uniform, near-zero Δ17O values as refractory inclusions and ice were much less abundant in the inner solar system. The two populations were plausibly mixed together by the Grand Tack when Jupiter and Saturn migrated inward emptying and then repopulating the asteroid belt with roughly equal masses of planetesimals from inside and outside Jupiter’s orbit (S- and C-type asteroids).

An Approach to Diagnosis and Endovascular Treatment of Refractory Ascites in Liver Transplant: A Pictorial Essay and Clinical Practice Algorithm.

PubMed

Pereira, Keith; Salsamendi, Jason; Fan, Ji

2015-10-01

Recipients of liver transplant are surviving longer as both the surgical procedure and postsurgical care have improved. Despite improvements, serious complications from the procedure remain that significantly affect patient outcome and may result in retransplant. Refractory ascites is one complication, occurring in about 5.6% of transplant recipients. Management of refractory ascites after liver transplant presents a challenge to the multidisciplinary team caring for these patients. We discuss approaches to the diagnosis and treatment of refractory ascites after liver transplant, based on a literature review, with a primary focus on vascular causes. These approaches are illustrated by case examples highlighting our experiences at an academic tertiary medical center. We propose a clinical practice algorithm for optimal endovascular treatment of refractory ascites after liver transplant. The cornerstone of refractory ascites care is diagnosis and treatment of the cause. Vascular causes are not infrequently encountered and, if not treated early, are associated with graft loss and high morbidity and mortality and are major indications for retransplant. For patients with recurrent disease or graft rejection needing large volume paracentesis, the use of a transjugular intrahepatic portosystemic shunt may serve as a bridge to more definitive treatment (retransplant), although it may not be as effective for managing ascites as splenic artery embolization, arguably underused, which is emerging as a potential alternative treatment option. A multidisciplinary strategy for the diagnosis and care of patients with refractory ascites after liver transplant is crucial, with endovascular treatment playing an important role. The aim is for this document to serve as a concise and informative reference to be used by those who may care for patients with this rare yet serious diagnosis.

Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

PubMed

Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

2017-01-01

Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P < 0.05), the complete bolus transit ( P < 0.01), and the residual pressure of lower esophageal sphincter ( P < 0.05) in these patients. The overall score ( P < 0.01) and the subscale scores of acid reflux syndrome ( P < 0.05), abdominal pain ( P < 0.05), and indigestion syndrome ( P < 0.01) in the Gastrointestinal Symptom Rating Scale were significantly improved by the 8-week RKT treatment. In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

Dynamics of occurrence of refractory coeliac disease and associated complications over 25 years.

PubMed

Eigner, W; Bashir, K; Primas, C; Kazemi-Shirazi, L; Wrba, F; Trauner, M; Vogelsang, H

2017-01-01

Refractory coeliac disease, enteropathy associated T-cell lymphoma and small bowel adenocarcinoma are rare but prognostically important complications in coeliac disease. To analyse potential changes in occurrence of complicated coeliac disease over the last 25 years. One thousand one hundred and thirty eight patients were included and evaluated based on their time of first presentation at the Medical University of Vienna, Austria. Occurrences of refractory coeliac disease and associated malignancies were evaluated for 5-year intervals from January 1990 until December 2014 and were compared over time. 2.6% (n = 29) were diagnosed with refractory coeliac disease (females 65.6%, mean age at diagnosis 62.8 years). The proportion of those patients was 2.6%, 3.1%, 3.3%, 2.7% and 0.5% for the 5 year intervals from 1990 onwards. Thus, the number of refractory cases has been decreasing since 2000 (P = 0.024). The number of patients presenting with lymphoma (n = 7) was 0.6%, 0.4%, 1.1%, 0.8% and 0% from 1990 to 2014. Similarly the number of patients with adenocarcinoma (n = 4) decreased to 0% until 2014. Overall mortality in patients suffering from refractory disease was 48%. Of all patients diagnosed with lymphoma 71.4% died with a 5-year survival rate of 28.6%. Over the past 15 years the occurrence of complicated coeliac disease has been decreasing. This possibly reflects a higher awareness of coeliac disease and optimised diagnosis and treatment with avoidance of long-term immunological disease activity. Symptomatic disease and a delay in diagnosis are risk factors for refractory coeliac disease and related cancer. © 2016 John Wiley & Sons Ltd.

Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment?

PubMed

Hautvast, R W; DeJongste, M J; ter Horst, G J; Blanksma, P K; Lie, K I

1996-07-01

The treatment of angina pectoris as a symptom of coronary artery disease usually is focused on restoring the balance between oxygen demand and supply of the myocardium by administration of drugs interfering in heart rate, cardiac pre- and afterload, and coronary vascular tone. For nonresponders to drug therapy or for those with jeopardized myocardium, revascularization procedures such as coronary bypass surgery and percutaneous transluminal coronary angioplasty are at hand. However, the atherosclerotic process is not stopped by these therapies and, at longer terms, angina may recur. It is not always possible to revascularize all the patients who do not positively react to medical treatment. Those with angina, not responding to adequate medication and who are not suitable anymore for revascularization, are considered to suffer from refractory angina pectoris. This group of patients has a poor quality of life, for their exercise tolerance is severely afflicted. For these patients, neurostimulation has been described repeatedly as an effective and safe therapy. The mechanism of action of neurostimulation is not completely known, but recent studies suggest an anti-ischemic effect, exerted through changes in myocardial blood flow. As soon as its safety is sufficiently established, it may become a useful alternative in the treatment of refractory angina pectoris.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

PubMed Central

Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

2009-01-01

Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

Retrospective Analysis of Nonepileptic Patients With Isolated Epileptiform Discharges Treated With Anticonvulsants.

PubMed

Swatzyna, Ronald J; Tarnow, Jay D; Proler, Meyer L; Roark, Alexandra J; MacInerney, Erin K; Kozlowski, Gerald P

2017-09-01

Many antiepileptic drugs (AEDs) have been tested on nonepileptic patients with a variety of diagnoses. The Food and Drug Administration has only approved certain AEDs for a small number of psychiatric conditions. There are few studies of nonepileptic patients that recommend an empirical trial of AEDs when isolated epileptiform discharges (IEDs) are identified in the electroencephalogram (EEG). However, no trials have been published. The purpose of this study is to evaluate the outcome of treating nonepileptic patients with AEDs when IEDs are present. Refractory cases were reviewed from a multidisciplinary practice whose EEG readings contained IEDs and were subsequently medicated with anticonvulsants by the clinic's psychiatrist. The psychiatrist's progress notes were assessed to determine the impact of adding anticonvulsants based on parent reports, teacher reports, and clinical observation. The final sample was composed of 76 refractory cases. Of the 76 patients treated with anticonvulsants, the majority were found to be improved in follow-up progress notes: 65 improved (85.53%), 6 unchanged (7.89%), and 5 more severe (6.58%). These observational findings suggest that further studies will be needed to show that IEDs may predict positive treatment outcome to anticonvulsant medication and act as a step toward an evidence-based treatment. Also, EEG screening may prove to be useful for refractory cases regardless of age, gender, or diagnosis.

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study.

PubMed

Hausman-Kedem, Moran; Menascu, Shay; Kramer, Uri

2018-04-16

The objective of this observational study was to evaluate the efficacy of medical cannabis for the treatment of refractory epilepsy. Fifty-seven patients (age 1-20 years) with epilepsy of various etiologies were treated with Cannabis oil extract (CBD/THC ratio of 20:1) for at least 3 months (Median follow up time-18 months). Forty-Six Patients were included in the efficacy analysis. Average CBD dose was11.4 mg/kg/d. Twenty-six patients (56%) had ≤50% reduction in mean monthly seizure frequency. There was no statistically significant difference in response rate among various epilepsy etiologies, and cannabis strain used. Younger age at treatment onset (<10 years) and higher CBD dose (>11 mg/kg/d) were associated with better response to treatment. Adverse reactions were reported in 46% of patients and were the main reason for treatment cessation. Our results suggest that adding CBD-enriched cannabis extract to the treatment regimen of patients with refractory epilepsy may result in a significant reduction in seizure frequency according to parental reports. Randomized controlled trials are necessary to assess its true efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

A Case of Treatment- resistant Depression and Body Dysmorphic Disorder: The Role of Electroconvulsive Therapy Revisited.

PubMed

Mahato, Ram S; San Gabriel, Maria Chona P; Longshore, Carrol T; Schnur, David B

2016-01-01

Body dysmorphic disorder is a common, often disabling condition, and is frequently comorbid with major depressive disorder. Selective serotonin reuptake inhibitors constitute first line set of somatic interventions but the management of refractory patients remains challenging. Electroconvulsive therapy, an often highly beneficial treatment for medication resistant-depression, is not considered an effective therapeutic alternative for treatment refractory body dysmorphic disorder. Here we present a 50-year-old woman with body dysmorphic disorder and comorbid major depressive disorder who remained incapacitated and suicidal despite several trials with selective serotonin reuptake inhibitors and antipsychotic medication. Depressive and dysmorphic symptoms appeared to resolve with electroconvulsive therapy, and remission was sustained for two months. Electroconvulsive therapy has an important place in the management of treatment- resistant depression associated with body dysmorphic disorder, and, in select cases, may be effective for dysmorphic symptoms as well.

[The last phase in the progressive neoplasic disease: care at the end-of-life, refractory symptoms and sedation].

PubMed

González Barón, Manuel; Gómez Raposo, César; Vilches Aguirre, Yolanda

2006-09-23

End-of-life is one of the most stressful phases during course of a neoplasic disease. Frequently, death of patients with cancer comes after a continuous and progressive physical impairment. As death approaches, the medical team might redefine outcomes and treat as priority symptoms and relief suffering. That care encompasses the physical, psychological, social, spiritual, and existential needs of patients and their families. However, symptoms are frequently observed that are intolerable for the patient and which do not respond to usual palliative measures. The intolerable nature and being refractory to treatment indicates to the health-care team, on many occasions, the need for sedation of the patient. The medical team can take comfort in the knowledge that they did their best to provide safe passage to all their patients and that, although they did not always cure them, the patients often were healed.

Extra-adrenal phaeochromocytoma—a case report of refractory hypertension

PubMed Central

Singh, V.P.; Singh, Manjeet; Malhotra, Mridul; Kumar, Ashok; Agarwal, A.K.

2012-01-01

There are at least 5% of all hypertensive patients whose blood pressure (BP) remains elevated despite adequate treatment. In these cases, the clinician is forced to search for a secondary cause of the chronic BP elevation. Certain environmental factors are known to induce resistant-hypertension. Additionally, there may be pseudo-resistance occurring or the patient may be suffering from a secondary form of hypertension such as renovascular or endocrinological hypertension (phaeochromocytoma, Cushing's syndrome, etc.). We report a case of extra-adrenal phaeochromocytoma who was on adequate antihypertensive medications but remained refractory to treatment prior to the exact diagnosis. PMID:22572502

Successful treatment of refractory hepatic lymphorrhea after gastrectomy for early gastric cancer, using surgical ligation and subsequent OK-432 (Picibanil) sclerotherapy.

PubMed

Tanaka, Kouji; Ohmori, Yukinari; Mohri, Yasuhiko; Tonouchi, Hitoshi; Suematsu, Mina; Taguchi, Yukiko; Adachi, Yukihiko; Kusunoki, Masato

2004-01-01

Postoperative hepatic lymphorrhea is a very rare complication after abdominal surgery. Hepatic lymphorrhea, not containing chyle, involves an internal lymph fistula between the lymphatic channels toward the cisterna chyli and the peritoneal cavity. Over the past 20 years, 17 cases have been reported in Japan. Here, we report a further case, of a patient with successfully treated intractable hepatic lymphorrhea following gastrectomy for early gastric cancer. We review 18 cases, including the present case, with respect to the management of postoperative lymphorrhea refractory to conventional medical treatment.

Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy.

PubMed

Klinger, Neil V; Mittal, Sandeep

2016-01-01

Epilepsy affects 50 million people worldwide and about 30% of these patients will not be adequately controlled with antiepileptic drugs (AEDs) alone. For patients where resective surgery is not indicated, deep brain stimulation (DBS) may be an effective alternative. The majority of available literature targets the thalamic nuclei (anterior; centromedian), subthalamic nucleus, hippocampus, and cerebellum. Here, we review patient outcomes and adverse events related to DBS to these various targets. Data show DBS may be a safe and effective treatment option for refractory epilepsy. Copyright © 2015. Published by Elsevier B.V.

[A study of epilepsy according to the age at onset and monitored for 3 years in a regional reference paediatric neurology unit].

PubMed

Ochoa-Gómez, Laura; López-Pisón, Javier; Lapresta Moros, Carlos; Fuertes Rodrigo, Cristina; Fernando Martínez, Ruth; Samper-Villagrasa, Pilar; Monge-Galindo, Lorena; Peña-Segura, José Luis; García-Jiménez, María Concepción

2017-01-01

A study of epilepsy, according to the age at onset of the crisis and its causes, monitored by a Paediatric Neurology Unit over a period of three years. Historical cohorts study was conducted by reviewing the Paediatric Neurology medical records data base of epileptic children followed-up from 1 January 2008 to 31 December 2010. A total of 4,595 children were attended during the study period. The diagnosis of epilepsy was established in 605 (13.17%): 277 (45.79%) symptomatic, 156 (25.79%) idiopathic, and 172 (28.43%) with cryptogenic epilepsy. Absence epilepsy and benign childhood epilepsy with centro-temporal spikes are the idiopathic epileptic syndromes most prevalent, and the most prevalent symptomatic epilepsies are prenatal encephalopathies. More than one-quarter (26.12%) of epilepsies began in the first year of life, and 67.72% were symptomatic. Refractory epilepsy was observed in 25.29%, 42.46% with cognitive impairment, 26.45% with motor involvement, and 9.92% with an autism spectrum disorder, being more frequent at an earlier age of onset. The absence of a universally accepted classification of epileptic syndromes makes tasks like this difficult, starting with the terminology. A useful classification would be aetiological, with two groups: a large group with established aetiology, or very likely genetic syndromes, and another with no established cause. The age of onset of epilepsy in each aetiological group helps in the prognosis, which is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain aetiologies. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Epilepsy surgery and neurocysticercosis: Assessing the role of the cysticercotic lesion in medically-refractory epilepsy.

PubMed

Escalaya, Alejandro L; Burneo, Jorge G

2017-11-01

There is increasing evidence of the existence of refractoriness to treatment with antiepileptic medications in those with NCC-related epilepsy. We performed a systematic review with the objective to determine the role of a cysticercotic lesion in this group of patients. We sought those manuscripts, including case reports, describing patients with NCC-related medically-intractable epilepsy who underwent epilepsy surgery and were seizure-free a year after. Only 10 manuscripts fulfilled inclusion and exclusion criteria. Three different clinical presentations were identified: 1) the cysticercotic lesion was epileptogenic, 2) there was dual pathology, including the cysticercotic lesion, with the other lesion usually being hippocampal sclerosis, and 3) the cysticercotic lesion was not related to the epileptogenic focus. In the case of an epileptogenic cysticercotic lesion, the presence of gliosis appeared to be the culprit for epileptogenicity. More studies using large cohorts of patients might be able to confirm our findings. This article is part of a Special issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

Palliative Sedation in Patients With Cancer.

PubMed

Maltoni, Marco; Setola, Elisabetta

2015-10-01

Palliative sedation involves the use of sedative medication to relieve refractory symptoms in patients by reducing their level of consciousness. Although it is considered an acceptable clinical practice from most ethical points of view, palliative sedation is still a widely debated procedure and merits better understanding. The relevant medical literature pertaining to palliative sedation was analyzed and reviewed from various technical, relational, and bioethical perspectives. Proportionate palliative sedation is considered to be the most clinically appropriate modality for performing palliative sedation. However, guidelines must be followed to ensure that it is performed correctly. Benzodiazepines represent the first therapeutic option and careful monitoring of dosages is essential to avoid oversedation or undersedation. Proportionate palliative sedation is used to manage and relieve refractory symptoms in patients with cancer during their last days or hours of life. Evidence suggests that its use has no detrimental effect on survival. A different decision-making process is used to manage the withdrawal of hydration than the process used to determine whether proportionate palliative sedation is appropriate. Communication between patients, their relatives, and the health care staff is important during this medical intervention.

Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris.

PubMed

Konigstein, Maayan; Verheye, Stefan; Jolicœur, E Marc; Banai, Shmuel

2016-01-01

Alongside the remarkable advances in medical and invasive therapies for the treatment of ischemic heart disease, an increasing number of patients with advanced coronary artery disease unsuitable for revascularization continue to suffer from angina pectoris despite optimal medical therapy. Patients with chronic angina have poor quality of life and increased levels of anxiety and depression. A considerable number of innovative therapeutic modalities for the treatment of chronic angina have been investigated over the years; however, none of these therapeutic options has become a standard of care, and none are widely utilized. Current treatment options for refractory angina focus on medical therapy and secondary risk factor modification. Interventions to create increased pressure in the coronary sinus may alleviate myocardial ischemia by forcing redistribution of coronary blood flow from the less ischemic subepicardium to the more ischemic subendocardium, thus relieving symptoms of ischemia. Percutaneous, transvenous implantation of a balloon expandable, hourglass-shaped, stainless steel mesh in the coronary sinus to create a fixed focal narrowing and to increase backwards pressure, may serve as a new device-based therapy destined for the treatment of refractory angina pectoris.

Current Standard and Investigational Approaches to the Management of Hormone-Refractory Prostate Cancer

PubMed Central

Mendiratta, Prateek; Armstrong, Andrew J; George, Daniel J

2007-01-01

Prostate cancer is a common cause of death in men and remains incurable in the metastatic setting. In 2004, 2 landmark trials using docetaxel-based chemotherapy, TAX 327 and SWOG 99-16, showed a survival benefit for the first time in metastatic, hormone-refractory prostate cancer. Current research suggests that several distinct mechanisms of androgen-refractory disease may converge in patients with disease progression on androgen deprivation therapy. These findings have identified several potential targets for therapeutic intervention. Current standard and investigational treatment options for this disease are discussed, including chemotherapy and rapidly evolving therapies in phase II/III trials involving antiangiogenic therapies, signal transduction inhibitors, immunomodulatory agents, and nuclear receptor targets. In light of a growing array of treatment options and an increasingly chronic natural history, this review supports a multidisciplinary care approach to these patients, including medical oncologists, urologists, and radiation oncologists, to optimize survival and quality of life. PMID:17387372

Measuring Safety: A New Perspective on Outcomes of a Long-Term Intensive Case Management Program

DTIC Science & Technology

2005-05-01

treatment; complex treatment regimen, like electroconvulsive therapy (ECT), or new technologies; discharge against medical advice from inpatient...treatment; refractory to medication interventions; and need for therapy or psychiatric nursing in the home. While patients meeting the high acuity case...outpatient settings; individual, group, and family therapy ; and chemical dependency services. Exceptions to benefit limits were granted as needed, per

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

PubMed Central

Sanz-García, Ancor; Vega-Zelaya, Lorena; Pastor, Jesús; Torres, Cristina V.; Sola, Rafael G.; Ortega, Guillermo J.

2016-01-01

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area. PMID:28060326

[Recurrent retrieval of the core episode referred to as the onset of schizophrenia--psychopathological study on the autobiographical memory of the onset of the illness].

PubMed

Shimizu, Mitsue; Kato, Satoshi

2002-01-01

In this study, we explore the onset of psychotic episodes in schizophrenia. Patients with schizophrenia have sometimes reported specific life-events at the period of onset. For example: "It started on my 22nd birthday. From that day onward, my life was colored with extremes of happiness and tragedies", or "It was when I was playing with a cat in the park of S temple that I realized suddenly that my 'I'-ness had completely changed." In each case, patients referred to a specific event as a critical moment when the meaning of selfness and the surrounding world had changed. Interestingly, these moments were reported repeatedly throughout the history of their illnesses. We termed these clinical phenomena "Recurrent retrieval of the core episode referred to as the onset of schizophrenia" and investigated their psychopathologic implication. The autobiographical memory of nine schizophrenic patients with "Recurrent retrieval of the core episode referred to as the onset of schizophrenia" was investigated. Four representative cases are described in detail. Samples of subjective statements were collected from medical records and analyzed. 1) Form and content of the statement: Patients clearly referred to a specific moment in their life. They usually reported that their image of self or the world had completely changed. The content of their reports were always about the same theme. 2) Chronological pattern of the repetition: Although the reported life event occurred just before onset, the reminiscence usually occurred not only at the beginning of the refractory period but also at the beginning of the recovery period. Patients did not report such events when they were stable. In the refractory period, distinct symptoms of schizophrenia were observed after the reminiscence. In the recovery period, the reminiscence was accompanied by minor physical symptoms, such as fever elevation or gastrointestinal dysfunction. 3) Subjective characteristics of repetitive reminiscence: In the refractory period, patients relived the onset of schizophrenia by reporting it reminiscently. They were excited, in a state of high-tension, or feeling oppressed. In contrast, in the recovery period, they reported the critical moment in an emotionally stable state, and even recollected it with humor. They were able to maintain some emotional distance from the reminiscence. 4) Predictive factor on prognosis: Reminiscence in the recovery period predicted a good prognosis. Seven of nine such cases were in remission. Two patients with whom the reminiscence was observed only in the refractory period were chronically ill. Therefore, two patterns of repetitive reminiscence of the critical moment should be discriminated. 1. The statements of patients were developed on the possibility that the critical event had not happened. Therefore, it can be postulated that their statements reconstructed a temporality open to any possible future: the moment just before the critical event might not have happened. The proper temporality associated with repetitive reminiscence should be distinguished from that of repetition of a traumatic memory in post-traumatic stress disorder. 2. From a therapeutic viewpoint, it is important to know to whom the discourse of the patient was addressed. In the refractory period, patients reported the repetitive reminiscence to anyone in a non-discriminating fashion. In contrast, in the recovery period, their discourse on the reminiscence was directed to a particular person with whom they were in close contact. The structure of the latter discourse was similar to that of neurotic patients in that they both demand acceptance from others. That is, the discourse structure of our patients was drastically changed in the recovery period. Reconstruction of the critical moment found in the recovery period was accomplished by the patient's discourse directed to another person, one from whom they could realize self-acceptance.

Rituximab as first choice for patients with refractory rheumatoid arthritis: cost-effectiveness analysis in Iran based on a systematic review and meta-analysis.

PubMed

Ahmadiani, Saeed; Nikfar, Shekoufeh; Karimi, Somayeh; Jamshidi, Ahmad Reza; Akbari-Sari, Ali; Kebriaeezadeh, Abbas

2016-09-01

The aim of this study was to evaluate the effectiveness and cost-effectiveness of using rituximab as first line for patients with refractory rheumatoid arthritis in comparison with continuing conventional DMARDs, from a perspective of health service governors. A systematic review was implemented through searching PubMed, Scopus and Cochrane Library. Quality assessment was performed by Jadad scale. After meta-analysis of ACR index results, QALY gain was calculated through mapping ACR index to HAQ and utility index. To measure the direct and indirect medical costs, a set of interviews with patients were applied. Thirty-two patients were selected from three referral rheumatology clinics in Tehran with definite diagnosis of refractory rheumatoid arthritis in the year before and treatment regimen of either rituximab or DMARDs within last year. Incremental cost-effectiveness ratio was calculated for base case and scenario of generic rituximab. Threefold of GDP per capita was considered as threshold of cost-effectiveness. Four studies were eligible to be considered in this systematic review. Total risk differences of 0.3 for achieving ACR20 criteria, 0.21 for ACR50 and 0.1 for ACR70 were calculated. Also mean of total medical costs of patients for 24 weeks were $3985 in rituximab group and $932 for DMARDs group. Thus, the incremental cost per QALY ratio will be $45,900-$70,223 in base case and $32,386-$49,550 for generic scenario. Rituximab for treatment of patients with refractory rheumatoid arthritis is not considered as cost-effective in Iran in none of the scenarios.

The Ahmed Glaucoma Valve in Refractory Glaucoma: Experiences in Southwest Ethiopia.

PubMed

Gessesse, Girum W

2015-07-01

The management of refractory glaucoma is a challenging task for any glaucoma surgeon. This study is aimed to evaluate the efficacy of Ahmed Glaucoma Valve implantation in refractory glaucomas in South-West Ethiopia. A retrospective review was conducted on the charts of consecutive patients treated with Ahmed glaucoma valve implantation at Jimma University Specialized Hospital between August 2012 and August 2014. Success was defined as Intraocular Pressure (IOP) less than 22 mm Hg and greater than 5mm Hg at 6 months, with at least 30% reduction from baseline, without medical therapy (complete success) or either with or without medication (qualified successes). A total of 12 eyes of 11 patients were included. The mean age of patients was 40.7 (SD= 19.0) years; 63.6% of them were males. The main types of glaucoma were pseudoexfoliative (3 eyes), uveitic (2 eyes), chronic angle closure (2 eyes) and Juvenile Open Angle (JOAG) (2 eyes). The mean IOP was reduced from preoperative level (32.75±7.14 mmHg) to (15.75 ±4.35 mmHg) at six postoperative months, (P<0.001); 66.7% eyes had complete successes while 83.3% had qualified success. Intra-operative complications were encountered in 2(16.7%) eyes, while 5/12 (41.7%) eyes had post-operative complications-hypotony (one with choroidal effusion) and progression of cataract in 2 eyes each. Hypertensive phase was diagnosed in 2(16.7%) eyes. The Ahmed glaucoma valve implant appears to be effective and relatively safe for treating complicated glaucomas with success rate comparable with those reported from other studies. Ahmed glaucoma valve, refractory glaucoma, complications, Ethiopia.

Subpial transection surgery for epilepsy.

PubMed

Krishnaiah, Balaji; Ramaratnam, Sridharan; Ranganathan, Lakshmi Narasimhan

2013-08-20

Nearly 30% of patients with epilepsy continue to have seizures in spite of several antiepileptic drug (AED) regimens. In such cases they are regarded as having refractory, or uncontrolled epilepsy.There is no universally accepted definition for uncontrolled or medically refractory epilepsy, but for the purpose of this review, we will consider seizures to be drug resistant if they failed to respond to a minimum of two AEDs. It is believed that early surgical intervention may prevent seizures at a younger age and improve the intellectual and social status of children. There are many types of surgery for refractory epilepsy with subpial transection being one. Our main aim is to determine the benefits and adverse effects of subpial transection for partial-onset seizures and generalised tonic-clonic seizures in children and adults. We searched the Cochrane Epilepsy Group Specialised Register (8 August 2013), The Cochrane Central Register of Controlled Trials (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8 August 2013). We did not impose any language restrictions. We considered all randomised and quasi-randomised parallel group studies either blinded or non-blinded. Two review authors (BK and SR) independently screened the trials identified by the search. The same two authors planned to independently assess the methodological quality of studies. If studies had been identified for inclusion, one author would have extracted the data and the other would have verified it. No relevant studies were found. There is no evidence to support or refute the use of subpial transection surgery for medically refractory cases of epilepsy. Well designed randomised controlled trials are needed in future to guide clinical practice.

Successful treatment of refractory seizures with phenobarbital, propofol, and medetomidine following congenital portosystemic shunt ligation in a dog.

PubMed

Heidenreich, Dorothee C; Giordano, Paola; Kirby, Barbara M

2016-11-01

To report a case of refractory seizures following congenital portosystemic shunt (CPSS) ligation that regained normal neurologic and hepatic function with novel treatment. Medical care included constant rate infusions (CRI) of propofol and medetomidine in conjunction with phenobarbital and supportive intensive care. A 2-year-old neutered male Bichon Frise was diagnosed with a single extrahepatic CPSS based on typical clinical signs, laboratory data, abdominal ultrasound, and computed tomographic angiography. Following initiation of standard medical treatment, a complete surgical ligation of the CPSS was performed. Recovery was uneventful until postligation neurologic dysfunction developed 54 hours after surgery. Seizures were controlled with phenobarbital (6 mg/kg IM q 12 h) and propofol CRI (0.3-0.6 mg/kg/min). Attempts to wean the dog from the propofol CRI resulted in recurrence of seizure activity until the addition of medetomidine CRI (0.016 μg/kg/min) 76 hours after initiation of drug-induced coma allowed gradual discontinuation of the propofol CRI. The dog regained full neurologic and hepatic function and had no further seizure activity apart from a small number of seizure episodes 5 and 22 months later. Adjustments in antiepileptic treatment resulted in no further neurologic dysfunction at 27-month follow-up. This report highlights the potential benefit of medetomidine CRI for treatment of postattenuation refractory seizures, which to date have proven impossible to predict and difficult to treat with high mortality rates and persistent neurological deficits in surviving animals. Neuroprotective, drug-sparing, and anti-hypertensive features of medetomidine might improve outcome in postligation refractory seizures. Further investigation and clinical application of medetomidine CRI may improve outcome in this complication of CPSS attenuation. © Veterinary Emergency and Critical Care Society 2015.

When Should We Give Up Filtration Surgery: Indications, Techniques and Results of Cyclodestruction.

PubMed

Masis Solano, Marisse; Huang, Guofu; Lin, Shan C

2017-01-01

Cyclodestructive procedures are traditionally used in cases of glaucoma that are refractory to medical and surgical therapy. The goal of this chapter is to describe the indications, contraindications, techniques, and pitfalls of cyclodestructive procedures, including transscleral cyclophotocoagulation (TCP), micropulse TCP (MP-TCP), endoscopic cyclophotocoagulation (ECP), and ultrasound cilioplasty. A literature search for cyclodestructive techniques was performed, and relevant studies were included for evaluation and review. It is encouraging that TCP seems relatively efficacious even for patients who have been refractory to other treatments, depending on the energy setting, follow-up period, and definition of success. Repeated TCP is often required. TCP was more often used in eyes with limited visual potential caused by severe forms of glaucoma than in eyes with good visual potential. Serious complications were significant vision loss, inflammation, hypotony, and phthisis. ECP came later into clinical use for the treatment of refractory glaucoma. ECP is able to specifically target the ciliary epithelium under direct viewing as compared to TCP, which is an indirect cyclodestructive procedure. In the literature, it has been demonstrated that ECP has overall good success with relatively low complication rates when used for adult forms of glaucoma. A new technology using MP-TCP is a promising alternative to conventional cyclophotocoagulation. Early evidence shows that MP-TCP has clinical utility and a good safety profile. Ultrasound cilioplasty is a possible alternative to laser cyclodestruction that is already being commercialized and is currently under investigation. Both TCP and ECP are effective cyclodestructive procedures and alternatives for the treatment of glaucoma refractory to medical and surgical therapy, though potential for serious complications exists. TCP, ECP, and ultrasound cilioplasty are being used increasingly as the primary surgery for various kinds and stages of glaucoma. © 2017 S. Karger AG, Basel.

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

PubMed

Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p < .01). In addition, the low International Prognostic Index, low Prognostic Index for T cell lymphoma, or normal level of LDH in serum was associated with favorable prognosis. Grade 3/4 adverse effect was observed in 10 of 25 patients treated with GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections.

PubMed

Tai, Xin You; Koepp, Matthias; Duncan, John S; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y W; Reeves, Cheryl; Michalak, Zuzanna; Thom, Maria

2016-09-01

SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = -0.63), recall (r = -0.44) and graded naming test scores (r = -0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = -0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ(2), P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections

PubMed Central

Tai, Xin You; Koepp, Matthias; Duncan, John S.; Fox, Nick; Thompson, Pamela; Baxendale, Sallie; Liu, Joan Y. W.; Reeves, Cheryl; Michalak, Zuzanna

2016-01-01

Abstract See Bernasconi (doi:10.1093/aww202) for a scientific commentary on this article. Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer’s disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer’s disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer’s disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = −0.63), recall (r = −0.44) and graded naming test scores (r = −0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = −0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ2, P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications. PMID:27497924

Interferon alpha-2a treatment for refractory Behcet uveitis in Korean patients.

PubMed

Lee, Ji Hwan; Lee, Christopher Seungkyu; Lee, Sung Chul

2018-02-20

To evaluate therapeutic outcomes of interferon alpha-2a (IFNα2a) treatment in patients with Behcet's disease who were refractory to immunosuppressive agents. This retrospective case series reviewed the medical records of 5 patients with refractory Behcet uveitis from January 2011 to February 2017. IFNα2a was administered at a dose of 3 million IU 3 times per week. Clinical response, relapse rate, and change of visual acuity were evaluated. The mean age of patients was 39.60 ± 9.21 years, and the median treatment duration was 6 months. Four of the 5 patients (80%) presented with responses to IFNα2a without any uveitis attack during the treatment period. The mean number of uveitis attacks/year per patient during the treatment was 0.40 ± 0.89. The mean log of the Minimum Angle of Resolution visual acuity improved from 1.44 ± 0.38 at baseline to 1.02 ± 0.58 at the final follow up. IFNα2a is an effective therapy for Behcet uveitis refractory to conventional immunosuppressants in Korean patients.

Trace elements in ocean ridge basalts

NASA Technical Reports Server (NTRS)

Kay, R. W.; Hubbard, N. J.

1978-01-01

A study is made of the trace elements found in ocean ridge basalts. General assumptions regarding melting behavior, trace element fractionation, and alteration effects are presented. Data on the trace elements are grouped according to refractory lithophile elements, refractory siderophile elements, and volatile metals. Variations in ocean ridge basalt chemistry are noted both for regional and temporal characteristics. Ocean ridge basalts are compared to other terrestrial basalts, such as those having La/Yb ratios greater than those of chondrites, and those having La/Yb ratios less than those of chondrites. It is found that (1) as compared to solar or chondrite ratios, ocean ridge basalts have low ratios of large, highly-charged elements to smaller less highly-charged elements, (2) ocean ridge basalts exhibit low ratios of volatile to nonvolatile elements, and (3) the transition metals Cr through Zn in ocean ridge basalts are not fractionated more than a factor of 2 or 3 from the chondritic abundance ratios.

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

PubMed Central

Carvalho, Benilton S.; Bilevicius, Elizabeth; Alvim, Marina K. M.; Lopes-Cendes, Iscia

2017-01-01

Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in ABCB1, ABCC2, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner. PMID:28052106

Clinical outcomes of Ahmed glaucoma valve implantation in pediatric glaucoma.

PubMed

Pakravan, Mohammad; Esfandiari, Hamed; Yazdani, Shahin; Doozandeh, Azadeh; Dastborhan, Zahra; Gerami, Ebrahim; Kheiri, Bahareh; Pakravan, Parastou; Yaseri, Mehdi; Hassanpour, Kiana

2018-03-01

To evaluate the outcomes of Ahmed glaucoma valve implantation in refractory primary congenital glaucoma as well as primary procedure in aphakic glaucoma. In this retrospective study, medical records of patients who underwent Ahmed glaucoma valve implantation for refractory glaucoma and aphakic glaucoma were reviewed. Primary outcome measures were the surgical success defined as intraocular pressure ≤21 mm Hg and decreased ≥20% and no secondary glaucoma surgery. Secondary outcome measures were the number of glaucoma medications, complications, best corrected visual acuity, and intraocular pressure. A total of 62 eyes of refractory primary congenital glaucoma patients (group 1) and 33 eyes of aphakic glaucoma patients (group 2) were included in our study. Mean follow-up was 51 ± 33 months in group 1 and 49 ± 41 months in group 2 (p = 0.82). The cumulative probability of success was 90% in both groups at the first year; however, the success rate was 52.5% in group 1 and 71.5% in group 2 at 5 years' follow-up visit. In group 1, the mean intraocular pressure ± standard deviation was 33.1 ± 8.6 mm Hg at the baseline and decreased to 17.1 ± 5.3 mm Hg at 1 year and 18.5 ± 6.4 at 3 years postoperatively (all p's < 0.001). Corresponding values for group 2 were 28.9 ± 6.1, 15.2 ± 4.6, and 16.0 ± 5.9 mm Hg, respectively (all p's < 0.001). The baseline number of glaucoma medications was 3 ± 0.7 that decreased to 2 ± 0.8 at final follow-up (p = 0.02). Ahmed glaucoma valve implantation has a moderate success rate in the management of refractory primary congenital glaucoma with an increased chance of tube-related complications. The surgical success rate is higher in case of primary Ahmed glaucoma valve implant for aphakic glaucoma with acceptable safety profile.

Variation in Anticonvulsant Selection and Electroencephalographic Monitoring Following Severe Traumatic Brain Injury in Children-Understanding Resource Availability in Sites Participating in a Comparative Effectiveness Study.

PubMed

Kurz, Jonathan E; Poloyac, Samuel M; Abend, Nicholas S; Fabio, Anthony; Bell, Michael J; Wainwright, Mark S

2016-07-01

Early posttraumatic seizures may contribute to worsened outcomes after traumatic brain injury. Evidence to guide the evaluation and management of early posttraumatic seizures in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring, seizure prophylaxis, and the management of early posttraumatic seizures to provide essential information for trial design and the development of posttraumatic seizure management pathways. Surveys were sent to site principal investigators at all 43 sites participating in the Approaches and Decisions in Acute Pediatric TBI trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to 1) implement continuous electroencephalographic monitoring, 2) posttraumatic seizure prophylaxis, 3) treat acute posttraumatic seizures, 4) treat status epilepticus and refractory status epilepticus, and 5) monitor antiseizure drug levels. Institutions comprised a mixture of free-standing children's hospitals and university medical centers across the United States and Europe. Site principal investigators of the Approaches and Decisions in Acute Pediatric TBI trial. None. Continuous electroencephalographic monitoring was available in the PICU in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic antiseizure medications is anticipated in children (93%); yet, a minority reports that a specified protocol for treatment of posttraumatic seizures is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for refractory status epilepticus (81%). The presence of treatment protocols for seizure prophylaxis, early posttraumatic seizures, posttraumatic status epilepticus, and refractory status epilepticus was associated with decreased reported medications (all p < 0.05). This study reports the current management practices for early posttraumatic seizures in select academic centers after pediatric severe traumatic brain injury. The substantial variation in continuous electroencephalographic monitoring implementation, choice of seizure prophylaxis medications, and management of early posttraumatic seizures across institutions was reported, signifying the areas of clinical uncertainty that will help provide focused design of clinical trials. Although sites with treatment protocols reported a decreased number of medications for the scenarios described, completion of the Approaches and Decisions in Acute Pediatric TBI trial will be able to determine if these protocols lead to decreased variability in medication administration in children at the clinical sites.

Candida Infections of Medical Devices

PubMed Central

Kojic, Erna M.; Darouiche, Rabih O.

2004-01-01

The number of indwelling medical devices is escalating, and an increasing proportion of device-related infections are being caused by Candida spp. Candida spp. produce biofilms on synthetic materials, which facilitates adhesion of the organisms to devices and renders them relatively refractory to medical therapy. Management of device-related Candida infections can be challenging. Removal of the infected device is generally needed to establish cure of Candida infections of medical devices. However, since the pathogenesis of Candida bloodstream infection is complicated, more studies are necessary to determine the role of catheter exchange in patients with both gastrointestinal tract mucositis and indwelling catheters. The medical and economic impact of these infections is enormous. PMID:15084500

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.

PubMed

Kim, Ji Eun; Gweon, Tae-Geun; Yeo, Chang Dong; Cho, Young-Seok; Kim, Gi Jun; Kim, Jae Young; Kim, Jong Wook; Kim, Hyunho; Lee, Hye Won; Lim, Taeseok; Ham, Hyoju; Oh, Hyun Jin; Lee, Yeongbok; Byeon, Jaeho; Park, Sung Soo

2014-09-21

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Resolution of electroconvulsive therapy refractory major depressive disorder with unintentional hypoglycemic seizure: a case report.

PubMed

Rosenblat, Joshua D; Devarajan, Sivakumaran

2013-09-01

We report a 74-year-old white woman with type 1 diabetes and major depressive disorder refractory to multiple medications who received 15 electroconvulsive therapy treatments with minimal improvement. After an accidental hypoglycemic seizure, the patient's symptoms completely resolved. In conclusion, the present case reveals an instance where electroconvulsive therapy-induced seizures appeared to be minimally effective, whereas a single accidental hypoglycemia-induced seizure was incredibly effective for the resolutions of depressive symptoms. Although this case presents a single efficacious use of accidental insulin coma therapy, the applicability is limited because of the known risks of insulin coma therapy.

Gastroesophageal Reflux Management with the LINX® System for Gastroesophageal Reflux Disease Following Laparoscopic Sleeve Gastrectomy.

PubMed

Desart, Kenneth; Rossidis, Georgios; Michel, Michael; Lux, Tamara; Ben-David, Kfir

2015-10-01

Laparoscopic sleeve gastrectomy (LSG) has gained significant popularity in the USA, and consequently resulted in patients experiencing new-onset gastroesophageal reflux disease (GERD) following this bariatric procedure. Patients with GERD refractory to medical therapy present a more challenging situation limiting the surgical options to further treat the de novo GERD symptoms since the gastric fundus to perform a fundoplication is no longer an option. The aim of this study is to determine if the LINX® magnetic sphincter augmentation system is a safe and effective option for patients with new gastroesophageal reflux disease following laparoscopic sleeve gastrectomy. This study was conducted at the University Medical Center. This is a retrospective review of seven consecutive patients who had a laparoscopic LINX® magnetic sphincter device placement for patients with refractory gastroesophageal reflux disease after laparoscopic sleeve gastrectomy between July 2014 and April 2015. All patients were noted to have self-reported greatly improved gastroesophageal reflux symptoms 2-4 weeks after their procedure. They were all noted to have statistically significant improved severity and frequency of their reflux, regurgitation, epigastric pain, sensation of fullness, dysphagia, and cough symptoms in their postoperative GERD symptoms compared with their preoperative evaluation. This is the first reported pilot case series, illustrating that the LINX® device is a safe and effective option in patients with de novo refractory gastroesophageal reflux disease after a laparoscopic sleeve gastrectomy despite appropriate weight loss.

Direct medical costs for partial refractory epilepsy in Mexico.

PubMed

García-Contreras, Fernando; Constantino-Casas, Patricia; Castro-Ríos, Angélica; Nevárez-Sida, Armando; Estrada Correa, Gloria del Carmen; Carlos Rivera, Fernando; Guzmán-Caniupan, Jorge; Torres-Arreola, Laura del Pilar; Contreras-Hernández, Iris; Mould-Quevedo, Joaquin; Garduño-Espinosa, Juan

2006-04-01

The aim was to determine the direct medical costs in patients with partial refractory epilepsy at the Mexican Institute of Social Security (IMSS) in Mexico. We carried out a multicenter, retrospective-cohort partial-economic evaluation study of partial refractory epilepsy (PRE) diagnosed patients and analyzed patient files from four secondary- and tertiary-level hospitals. PRE patients >12 years of age with two or more antiepileptic drugs and follow-up for at least 1 year were included. The perspective was institutional (IMSS). Only direct healthcare costs were considered, and the timeline was 1 year. Cost techniques were microcosting, average per-service cost, and per-day cost, all costs expressed in U.S. dollars (USD, 2004). We reviewed 813 files of PRE patients: 133 had a correct diagnosis, and only 72 met study inclusion criteria. Fifty eight percent were females, 64% were <35 years of age, 47% were students, in 73% maximum academic level achieved was high school, and 53% were single. Fifty one percent of cases experienced simple partial seizures and 94% had more than one monthly seizure. Annual healthcare cost of the 72 patients was 190,486 USD, ambulatory healthcare contributing 76% and hospital healthcare with 24%. Annual mean healthcare cost per PRE patient was 2,646 USD; time of disease evolution and severity of the patient's illness did not affect costs significantly.

Sedation in palliative care – a critical analysis of 7 years experience

PubMed Central

Muller-Busch, H Christof; Andres, Inge; Jehser, Thomas

2003-01-01

Background The administration of sedatives in terminally ill patients becomes an increasingly feasible medical option in end-of-life care. However, sedation for intractable distress has raised considerable medical and ethical concerns. In our study we provide a critical analysis of seven years experience with the application of sedation in the final phase of life in our palliative care unit. Methods Medical records of 548 patients, who died in the Palliative Care Unit of GK Havelhoehe between 1995–2002, were retrospectively analysed with regard to sedation in the last 48 hrs of life. The parameters of investigation included indication, choice and kind of sedation, prevalence of intolerable symptoms, patients' requests for sedation, state of consciousness and communication abilities during sedation. Critical evaluation included a comparison of the period between 1995–1999 and 2000–2002. Results 14.6% (n = 80) of the patients in palliative care had sedation given by the intravenous route in the last 48 hrs of their life according to internal guidelines. The annual frequency to apply sedation increased continuously from 7% in 1995 to 19% in 2002. Main indications shifted from refractory control of physical symptoms (dyspnoea, gastrointestinal, pain, bleeding and agitated delirium) to more psychological distress (panic-stricken fear, severe depression, refractory insomnia and other forms of affective decompensation). Patients' and relatives' requests for sedation in the final phase were significantly more frequent during the period 2000–2002. Conclusion Sedation in the terminal or final phase of life plays an increasing role in the management of intractable physical and psychological distress. Ethical concerns are raised by patients' requests and needs on the one hand, and the physicians' self-understanding on the other hand. Hence, ethically acceptable criteria and guidelines for the decision making are needed with special regard to the nature of refractory and intolerable symptoms, patients' informed consent and personal needs, the goals and aims of medical sedation in end-of-life care. PMID:12744722

Extracorporeal shockwave myocardial therapy is efficacious in improving symptoms in patients with refractory angina pectoris--a multicenter study.

PubMed

Prasad, Megha; Wan Ahmad, Wan Azman; Sukmawan, Renan; Magsombol, Edward-Bengie L; Cassar, Andrew; Vinshtok, Yuri; Ismail, Muhammad Dzafir; Mahmood Zuhdi, Ahmad Syadi; Locnen, Sue Ann; Jimenez, Rodney; Callleja, Homobono; Lerman, Amir

2015-05-01

Medically refractory angina remains a significant health concern despite major advances in revascularization techniques and emerging medical therapies. We aimed to determine the safety and efficacy of extracorporeal shockwave myocardial therapy (ESMT) in managing angina pectoris. A single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II-IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3-6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT. The mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients. This multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.

Refractory overactive bladder: Beyond oral anticholinergic therapy

PubMed Central

Glinski, Ronald W.; Siegel, Steven

2007-01-01

Objectives: In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments. Materials and Methods: A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options. Results: In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted. Conclusion: The vast majority of OAB patients can be managed successfully by behavioral options with or without anticholinergic medications. When those fail, neuromodulation or intravesical botulinum toxin therapies are successful alternatives for most of the remaining group. We encourage practitioners responsible for the care of OAB patients to gain experience with these options. More research is needed to assess the cost-effectiveness of various OAB treatments PMID:19675795

Safety and efficacy of extracorporeal shock wave myocardial revascularization therapy for refractory angina pectoris.

PubMed

Cassar, Andrew; Prasad, Megha; Rodriguez-Porcel, Martin; Reeder, Guy S; Karia, Darshak; DeMaria, Anthony N; Lerman, Amir

2014-03-01

To assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris. A single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires. Fifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10). In this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder-neck dysfunction: objective and patient-reported outcomes.

PubMed

Sacco, Emilio; Tienforti, Daniele; Bientinesi, Riccardo; D'Addessi, Alessandro; Racioppi, Marco; Pinto, Francesco; Totaro, Angelo; Vittori, Matteo; D'Agostino, Daniele; Bassi, Pierfrancesco

2014-01-01

To determine efficacy and safety of OnabotulinumtoxinA (BoNT-A) injection therapy in medically refractory patients with lower urinary tract symptoms (LUTS) due to primary bladder-neck dysfunction (PBND). Thirty-five consecutive ambulatory males diagnosed with PBND and refractory to medical therapy, with IPSS > 15, Qmax < 15 ml/sec, and total prostate volume < 30 cm(3), were screened from January 2010 to December 2011. Eligible patients underwent transurethral bladder-neck injection of BoNT-A (200 U, 50 U/ml × 4 sites) and were assessed at baseline, 2-, 6-, 9-, and 12-month postprocedure and until duration of clinical response. The primary outcome was the change from baseline in total IPSS, and secondary outcome were storage- and voiding-IPSS, QoL score, Qmax, and postvoiding residual volume (PVR), patient-reported outcomes. Adverse effects were also recorded, including ejaculatory dysfunctions. Of 30 enrolled patients (mean age 33.8 years), 29 (96.7%) completed the study. A statistically significant improvement of total IPSS was observed from 21.9 at baseline, to 7.8, 10.3, and 16.6 at 2, 6, and 9 months, respectively (P < 0.000). Statistically significant improvements from baseline of storage- and voiding-IPSS, QoL score, Qmax, and PVR were also observed until 9-month postprocedure. The proportion of patients with overall satisfaction was favorable although decreasing from 80% at 2 months, to 44.8% at 12 months. No significant adverse effects or ejaculatory dysfunctions were noted. BoNT-A injection therapy appears effective and safe in medically refractory men with PBND, although repeated procedures are required for long-term sustained benefit. Randomized controlled trials are warranted in order to corroborate these results. © 2013 Wiley Periodicals, Inc.

Greater occipital nerve excision for occipital neuralgia refractory to nerve decompression.

PubMed

Ducic, Ivica; Felder, John M; Khan, Neelam; Youn, Sojin

2014-02-01

Patients who undergo occipital nerve decompression for treatment of migraine headaches due to occipital neuralgia have already exhausted medical options for treatment. When surgical decompression fails, it is unknown how best to help these patients. We examine our experience performing greater occipital nerve (GON) excision for pain relief in this select, refractory group of patients. A retrospective chart review supplemented by a follow-up survey was performed on all patients under the care of the senior author who had undergone GON excision after failing occipital nerve decompression. Headache severity was measured by the migraine headache index (MHI) and disability by the migraine disability assessment. Success rate was considered the percentage of patients who experienced a 50% or greater reduction in MHI at final follow-up. Seventy-one of 108 patients responded to the follow-up survey and were included in the study. Average follow-up was 33 months. The success rate of surgery was 70.4%; 41% of patients showed a 90% or greater decrease in MHI. The MHI changed, on average, from 146 to 49, for an average reduction of 63% (P < 0.001). Migraine disability assessment scores decreased by an average of 49% (P < 0.001). Multivariate analysis revealed that a diagnosis of cervicogenic headache was associated with failure of surgery. The most common adverse effect was bothersome numbness or hypersensitivity in the denervated area, occurring in up to 31% of patients. Excision of the GON is a valid option for pain relief in patients with occipital headaches refractory to both medical treatment and surgical decompression. Potential risks include failure in patients with cervicogenic headache and hypersensitivity of the denervated area. To provide the best outcome to these patients who have failed all previous medical and surgical treatments, a multidisciplinary team approach remains critical.

Cost-utility analysis of intravenous immunoglobulin for the treatment of steroid-refractory dermatomyositis in Thailand.

PubMed

Bamrungsawad, Naruemon; Chaiyakunapruk, Nathorn; Upakdee, Nilawan; Pratoomsoot, Chayanin; Sruamsiri, Rosarin; Dilokthornsakul, Piyameth

2015-05-01

Intravenous immunoglobulin (IVIG) has been shown to be effective in treating steroid-refractory dermatomyositis (DM). There remains no evidence of its cost-effectiveness in Thailand. Our objective was to estimate the cost utility of IVIG as a second-line therapy in steroid-refractory DM in Thailand. A Markov model was developed to estimate the relevant costs and health benefits for IVIG plus corticosteroids in comparison with immunosuppressant plus corticosteroids in steroid-refractory DM from a societal perspective over a patient's lifetime. The effectiveness and utility parameters were obtained from clinical literature, meta-analyses, medical record reviews, and patient interviews, whereas cost data were obtained from an electronic hospital database and patient interviews. Costs are presented in $US, year 2012 values. All future costs and outcomes were discounted at a rate of 3% per annum. One-way and probabilistic sensitivity analyses were also performed. Over a lifetime horizon, the model estimated treatment under IVIG plus corticosteroids to be cost saving compared with immunosuppressant plus corticosteroids, where the saving of costs and incremental quality-adjusted life-years (QALYs) were $US4738.92 and 1.96 QALYs, respectively. Sensitivity analyses revealed that probability of response of immunosuppressant plus corticosteroids was the most influential parameter on incremental QALYs and costs. At a societal willingness-to-pay threshold in Thailand of $US5148 per QALY gained, the probability of IVIG being cost effective was 97.6%. The use of IVIG plus corticosteroids is cost saving compared with treatment with immunosuppressant plus corticosteroids in Thai patients with steroid-refractory DM. Policy makers should consider using our findings in their decision-making process for adding IVIG to corticosteroids as the second-line therapy for steroid-refractory DM patients.

Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children with ADHD

PubMed Central

Blader, Joseph C.; Pliszka, Steven R.; Jensen, Peter S.; Schooler, Nina R.; Kafantaris, Vivian

2010-01-01

OBJECTIVES The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol’s methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy often culminates in reduced aggression that averts the need for additional agents. PMID:20837589

Use of acalabrutinib in patients with mantle cell lymphoma.

PubMed

Awan, Farrukh T; Jurczak, Wojciech

2018-06-01

Acalabrutinib, a selective Bruton tyrosine kinase (BTK) inhibitor, was granted accelerated approval by the FDA on 31 October 2017 for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Areas covered: This narrative review provides an overview of acalabrutinib, its use in clinical practice and potential future developments. Expert commentary: BTK inhibitors have demonstrated efficacy in patients with relapsed or refractory MCL. To prepare patients for therapy, all preexisting infections should be diagnosed and treated, and infection prophylaxis undertaken. Serious adverse reactions are rare with acalabrutinib; however, patients should be made aware of common adverse events such as headaches, which usually resolve within one month without medical treatment. Interaction with other drugs appears to be less of an issue with acalabrutinib than with ibrutinib; however, patients receiving acalabrutinib therapy must be advised not to take any additional medications without first consulting with their treating physician. A key unmet medical need is treatment options for patients in whom BTK inhibitors are discontinued, because of either intolerance or refractory disease. Patients not tolerating ibrutinib could be switched to acalabrutinib, which has improved selectivity and increased tolerability. First-line treatment with acalabrutinib is being investigated.

Clinical and immunologic effects of faecal microbiota transplantation in a patient with collagenous colitis

PubMed Central

Günaltay, Sezin; Rademacher, Lech; Hultgren Hörnquist, Elisabeth; Bohr, Johan

2017-01-01

One to six percent of patients with microscopic colitis are refractory to medical treatment. The effect of faecal microbiota transplantation (FMT) in active collagenous colitis (CC) has, to the best of our knowledge, never been reported before. Here, we report the effect of repeated FMT in a patient with CC. The patient presented with severe symptoms including profuse diarrhea and profound weight loss. Although she responded to budesonide in the beginning, she became gradually refractory to medical treatment, and was therefore treated with FMT. The patient remained in remission for 11 mo after the third faecal transplantation. The immunomodulatory effect of the therapy was evaluated using flow cytometry, which showed alterations in the profile of intraepithelial and lamina propria lymphocyte subsets after the second transplantation. Our observations indicate that FMT can have an effect in CC, which support the hypothesis that luminal factors, influencing the intestinal microbiota, are involved in the pathogenesis of CC. PMID:28275312

Portal hypertension and gastrointestinal bleeding: Diagnosis, prevention and management

PubMed Central

Biecker, Erwin

2013-01-01

Bleeding from esophageal varices is a life threatening complication of portal hypertension. Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal. Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method. Therapy of acute bleeding is based on three strategies: vasopressor drugs like terlipressin, antibiotics and endoscopic therapy. In refractory bleeding, self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate. Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS. Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common. Possible medical and endoscopic treatment options are discussed. PMID:23964137

Refractory hypocalcemia precipitated by dual infection with typhoid fever and hepatitis A in a patient with congenital hypoparathyroidism.

PubMed

Karanth, Suman S; Bhat, Ram; Gupta, Anurag

2012-08-01

We present this rare occurrence of a 17 yr old boy, a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures. Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels. Investigations revealed severe hypocalcaemia (3.2 mg/dL), low 25 hydroxyvitamin D levels and hypomagnesaemia. The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes. Microbiological investigations were confirmatory for both hepatitis A and typhoid fever. In spite of the aggressive management with intravenous calcium gluconate infusion, refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels. We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Two magneto-encephalographic epileptic foci did not coincide with the electrocorticographic ictal onset zone in a patient with temporal lobe epilepsy.

PubMed

Hisada, K; Morioka, T; Nishio, S; Yamamoto, T; Fukui, M

2001-12-01

To evaluate the usefulness and limitations of magneto-encephalography (MEG) for epilepsy surgery, we compared 'interictal' epileptic spike fields on MEG with ictal electrocorticography (ECoG) using invasive chronic subdural electrodes in a patient with intractable medial temporal lobe epilepsy (MTLE) associated with vitamin K deficiency intracerebral hemorrhage. A 19-year-old male with an 8-year history of refractory complex partial seizures, secondarily generalized, and right hemispheric atrophy and porencephaly in the right frontal lobe on MRI, was studied with MEG to define the interictal paroxysmal sources based on the single-dipole model. This was followed by invasive ECoG monitoring to delineate the epileptogenic zone. MEG demonstrated two paroxysmal foci, one each on the right lateral temporal and frontal lobes. Ictal ECoG recordings revealed an ictal onset zone on the right medial temporal lobe, which was different from that defined by MEG. Anterior temporal lobectomy with hippocampectomy was performed and the patient has been seizure free for two years. Our results indicate that interictal MEG does not always define the epileptogenic zone in patients with MTLE.

Declarative long-term memory and the mesial temporal lobe: Insights from a 5-year postsurgery follow-up study on refractory temporal lobe epilepsy.

PubMed

Salvato, Gerardo; Scarpa, Pina; Francione, Stefano; Mai, Roberto; Tassi, Laura; Scarano, Elisa; Lo Russo, Giorgio; Bottini, Gabriella

2016-11-01

It is largely recognized that the mesial temporal lobe and its substructure support declarative long-term memory (LTM). So far, different theories have been suggested, and the organization of declarative verbal LTM in the brain is still a matter of debate. In the current study, we retrospectively selected 151 right-handed patients with temporal lobe epilepsy with and without hippocampal sclerosis, with a homogeneous (seizure-free) clinical outcome. We analyzed verbal memory performance within a normalized scores context, by means of prose recall and word paired-associate learning tasks. Patients were tested at presurgical baseline, 6months, 2 and 5years after anteromesial temporal lobe surgery, using parallel versions of the neuropsychological tests. Our main finding revealed a key involvement of the left temporal lobe and, in particular, of the left hippocampus in prose recall rather than word paired-associate task. We also confirmed that shorter duration of epilepsy, younger age, and withdrawal of antiepileptic drugs would predict a better memory outcome. When individual memory performance was taken into account, data showed that females affected by left temporal lobe epilepsy for longer duration were more at risk of presenting a clinically pathologic LTM at 5years after surgery. Taken together, these findings shed new light on verbal declarative memory in the mesial temporal lobe and on the behavioral signature of the functional reorganization after the surgical treatment of temporal lobe epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Charles Bonnet syndrome in hemianopia, following antero-mesial temporal lobectomy for drug-resistant epilepsy.

PubMed

Contardi, Sara; Rubboli, Guido; Giulioni, Marco; Michelucci, Roberto; Pizza, Fabio; Gardella, Elena; Pinardi, Federica; Bartolomei, Ilaria; Tassinari, Carlo Alberto

2007-09-01

Charles Bonnet syndrome (CBS) is a disorder characterized by the occurrence of complex visual hallucinations in patients with acquired impairment of vision and without psychiatric disorders. In spite of the high incidence of visual field defects following antero-mesial temporal lobectomy for refractory temporal lobe epilepsy, reports of CBS in patients who underwent this surgical procedure are surprisingly rare. We describe a patient operated on for drug-resistant epilepsy. As a result of left antero-mesial temporal resection, she presented right homonymous hemianopia. A few days after surgery, she started complaining of visual hallucinations, such as static or moving "Lilliputian" human figures, or countryside scenes, restricted to the hemianopic field. The patient was fully aware of their fictitious nature. These disturbances disappeared progressively over a few weeks. The incidence of CBS associated with visual field defects following epilepsy surgery might be underestimated. Patients with post-surgical CBS should be reassured that it is not an epileptic phenomenon, and that it has a benign, self-limiting, course which does not usually require treatment.

Pre- and Post-Clerkship Knowledge, Perceptions, and Acceptability of Electroconvulsive Therapy (ECT) in 3rd Year Medical Students.

PubMed

Ithman, Muaid; O'Connell, Chris; Ogunleye, Ayodeji; Lee, Suhwon; Chamberlain, Brett; Ramalingam, Anupama

2018-05-26

To examine the impact of the third year psychiatry clerkship on medical students' knowledge and opinion of ECT at University of Missouri-Columbia School of Medicine. Despite overwhelming evidence of ECT's efficacy and safety for refractory affective illnesses, (among other conditions), it remains a misunderstood and underutilized intervention. Several studies indicate that ECT stigma and misinformation, unfortunately, does not spare the medical community. Medical students are an optimal group to study, as they are forming their perspectives on different specialties. Few studies have measured the effect of education programs (e.g., clerkships, lectures, observation of ECT) on medical students' perspectives on ECT.

Surgical Considerations of Intractable Mesial Temporal Lobe Epilepsy

PubMed Central

Boling, Warren W.

2018-01-01

Surgery of temporal lobe epilepsy is the best opportunity for seizure freedom in medically intractable patients. The surgical approach has evolved to recognize the paramount importance of the mesial temporal structures in the majority of patients with temporal lobe epilepsy who have a seizure origin in the mesial temporal structures. For those individuals with medically intractable mesial temporal lobe epilepsy, a selective amygdalohippocampectomy surgery can be done that provides an excellent opportunity for seizure freedom and limits the resection to temporal lobe structures primarily involved in seizure genesis. PMID:29461485

Adult extracorporeal life support: a failed or forgotten concept?

PubMed

Colafranceschi, Alexandre Siciliano; Monteiro, Andrey José de Oliveira; Canale, Leonardo Secchin; Campos, Luiz Antonio de Almeida; Montera, Marcelo Westerlund; Silva, Paulo Roberto Dutra da; Fernandes, Marcelo Ramalho; Pinto, Alexandre de Araújo; Molas, Stelmar Moura; Mesquita, Evandro Tinoco

2008-07-01

The extracorporeal membrane oxygenation (ECMO) has been used in the neonatal and childhood periods with excellent results. The adult experience has been modest with inferior immediate results. The intermediate survival, however, has been promising. We have been using the extracorporeal membrane oxygenation for temporary mechanical circulatory support of adults that present with acute refractory cardiogenic shock in our institution. There is no other published experience of the use of this system in this scenario in Brazil. To describe our experience with the use of the extracorporeal membrane oxygenation for circulatory support in adults. Retrospective analysis of the medical files of patients submitted to the implant of extracorporeal membrane oxygenation system for circulatory assistance in acute and refractory cardiogenic shock. Eleven patients (63,5 yo; 45,5% male) were considered for analysis from 2005 to 2007. Median support time was 77 hours (10-240 h) and 5 patients have survived 30 days (45,5%). Two patients were subsequently submitted to prolonged paracorporeal circulatory assistance. Mortality on ECMO (6 patients) was due to multiple organ failure (66,6%) and refractory bleeding (33,4%). ECMO system is an option to be used in acute refractory cardiogenic shock as a bridge to recovery or selecting patients that might benefit from prolonged paracorporeal assist devices (bridge to bridge).

Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.

PubMed

Warner, Nafisseh S; Watson, James C; Bendel, Markus A; Moeschler, Susan M

2018-05-01

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

The epileptic amygdala: Toward the development of a neural prosthesis by temporally coded electrical stimulation.

PubMed

Cota, Vinícius Rosa; Drabowski, Bruna Marcela Bacellar; de Oliveira, Jasiara Carla; Moraes, Márcio Flávio Dutra

2016-06-01

Many patients with epilepsy do not obtain proper control of their seizures through conventional treatment. We review aspects of the pathophysiology underlying epileptic phenomena, with a special interest in the role of the amygdala, stressing the importance of hypersynchronism in both ictogenesis and epileptogenesis. We then review experimental studies on electrical stimulation of mesiotemporal epileptogenic areas, the amygdala included, as a means to treat medically refractory epilepsy. Regular high-frequency stimulation (HFS) commonly has anticonvulsant effects and sparse antiepileptogenic properties. On the other hand, HFS is related to acute and long-term increases in excitability related to direct neuronal activation, long-term potentiation, and kindling, raising concerns regarding its safety and jeopardizing in-depth understanding of its mechanisms. In turn, the safer regular low-frequency stimulation (LFS) has a robust antiepileptogenic effect, but its pro- or anticonvulsant effect seems to vary at random among studies. As an alternative, studies by our group on the development and investigation of temporally unstructured electrical stimulation applied to the amygdala have shown that nonperiodic stimulation (NPS), which is a nonstandard form of LFS, is capable of suppressing both acute and chronic spontaneous seizures. We hypothesize two noncompetitive mechanisms for the therapeutic role of amygdala in NPS, 1) a direct desynchronization of epileptic circuitry in the forebrain and brainstem and 2) an indirect desynchronization/inhibition through nucleus accumbens activation. We conclude by reintroducing the idea that hypersynchronism, rather than hyperexcitability, may be the key for epileptic phenomena and epilepsy treatment. © 2016 Wiley Periodicals, Inc.

The Use of Clozapine among Individuals with Intellectual Disability: A Review

ERIC Educational Resources Information Center

Singh, Ashvind N.; Matson, Johnny L.; Hill, B. D.; Pella, Russell D.; Cooper, Christopher L.; Adkins, Angela D.

2010-01-01

Clozapine has been approved in the United States since 1990 for refractory or treatment resistant schizophrenia in the general population. However, as with many other antipsychotic medications, it is being prescribed for reasons other than those indicated. Among individuals with intellectual disabilities, clozapine is increasingly being prescribed…

Obsessive Compulsive Disorder

PubMed Central

Goli, Veeraindar; Krishnan, Ranga; Ellinwood, Everett

1991-01-01

An estimated three to seven million Americans suffer from obsessive compulsive disorder at some time in their lives. Until recently, obsessive compulsive disorder was considered refractory to most treatments. However, recent studies indicate a better prognosis with behavioral therapy, antidepressant medications, or both. Behavioral treatment is generally more effective for compulsions than for obsessions. PMID:21229040

Refractory Depression, Fatigue, Irritable Bowel Syndrome, and Chronic Pain: A Functional Medicine Case Report.

PubMed

Plotnikoff, Gregory; Barber, Melissa

2016-01-01

Single-disorder or single-organ-system clinical practice guidelines are often of limited usefulness in guiding effective management of patients with chronic multidimensional signs and symptoms. The presence of multiple long-standing medical problems in a given patient despite intensive medical effort suggests that addressing systemic core imbalances could complement more narrowly focused approaches. A 72-year-old man experiencing longstanding depression, fatigue, irritable bowel syndrome, and chronic pain in the context of additional refractory illnesses was assessed and treated, guided by a system-oriented approach to underlying core imbalances termed functional medicine. This patient was referred from a team of clinicians representing primary care, cardiology, gastroenterology, hematology, and psychology. Prior treatment had been unsuccessful in managing multiple chronic comorbidities. Diagnostic assessment included comprehensive stool and nutritional/metabolic laboratory testing. The blood-, urine-, or stool-based measurements of relevant markers for multiple systemic issues, including digestion/absorption, inflammation, oxidative stress, and methylation, identified previously unrecognized root causes of his constellation of symptoms. These functional measurements guided rational recommendations for dietary choices and supplementation. The patient experienced steady and significant improvement in his mental health, fatigue, chronic pain, and irritable bowel syndrome-as well as the unexpected resolution of his chronic idiopathic pancytopenia. The success in this case suggests that other patients with chronic, complex, and treatment-refractory illness may benefit from a system-oriented assessment of core imbalances guided by specialized nutritional/metabolic and digestive laboratory testing.

Next-Step Strategies for Panic Disorder Refractory to Initial Pharmacotherapy

PubMed Central

Simon, NM; Otto, MW; Worthington, JJ; Hoge, EA; Thompson, EH; LeBeau, RT; Moshier, SJ; Zalta, AK; Pollack, MH

2010-01-01

Background More data is needed to guide next step interventions for panic disorder refractory to initial intervention. Method This 24-week randomized clinical trial (RCT) consisted of three phases. Phase 1 is a 6-week lead-in with open-label sertraline flexibly dosed to 100mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 is a six-week double blind RCT of (1) increased dose serotonin selective reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 is a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to “medication-optimization” (MO) with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent to treat sample in each phase. Results In Phase 1, 20.5% (8/39) achieved remission, and only baseline severity predicted endpoint PDSS (β (SE)= 1.04(0.15), t=6.76, p<0.000). In Phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n=2] vs. increased dose 9%[n=1]: FET p=n.s.). In Phase 3, remission was minimal (MO = 11%; CBT =10%), with a lack of group difference in PDSS reduction (t(df)=0.51(17), p>0.60) consistent with a small effect size (d=0.24). Conclusion Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in non-remitted panic after 12 weeks of an SSRI did not differ, suggesting both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest better predictors of response to specific treatments over time and additional interventions are needed. PMID:19814948

Decompressive craniectomy or medical management for refractory intracranial hypertension: an AAST-MIT propensity score analysis.

PubMed

Nirula, Ram; Millar, D; Greene, Tom; McFadden, Molly; Shah, Lubdha; Scalea, Thomas M; Stein, Deborah M; Magnotti, Louis J; Jurkovich, Gregory J; Vercruysse, Gary; Demetriades, Demetrios; Scherer, Lynette A; Peitzman, Andrew; Sperry, Jason; Beauchamp, Kathryn; Bell, Scott; Feiz-Erfan, Iman; O'Neill, Patrick; Coimbra, Raul

2014-04-01

Moderate/severe traumatic brain injury (TBI) management involves minimizing cerebral edema to maintain brain oxygen delivery. While medical therapy (MT) consisting of diuresis, hyperosmolar therapy, ventriculostomy, and barbiturate coma is the standard of care, decompressive craniectomy (DC) for refractory intracranial hypertension (ICH) has gained renewed interest. Since TBI treatment guidelines consider DC a second-tier intervention after MT failure, we sought to determine if early DC (<48 hours) was associated with improved survival in patients with refractory ICH. Eleven Level 1 trauma centers provided clinical data and head computed tomographic scans for patients with a Glasgow Coma Scale (GCS) score of 13 or less and radiographic evidence of TBI excluding deaths within 48 hours. Computed tomographic scans were graded according to the Marshall classification. A propensity score to receive DC (regardless of whether DC was performed) was calculated for each patient based on patient characteristics, physiology, injury severity, GCS, severity of intracranial injury, and treatment center. Patients who actually received a DC were matched to patients with similar propensity scores who received MT for analysis. Outcomes were compared between early (<48 hours of injury) primary or secondary DC and matched controls and then between early primary DC only and matched controls. There were 2,602 patients who met the inclusion criteria ,of whom 264 (10.1%) received DC (either primary or secondary to another cranial procedure) and 109 (5%) had a DC that was primary. Variables associated with performing a DC included sex, race, intracranial pressure monitor placement, in-house trauma attending, traumatic subarachnoid hemorrhage, midline shift, and basal cistern compression. There was no survival benefit with early primary DC compared with the controls (relative risk, 1.07; 95% confidence interval, 0.67-1.73; p = 0.77), and resource use was higher. Early DC does not seem to significantly improve mortality in patients with refractory ICH compared with MT. Neurosurgeons should pause before entertaining this resource-demanding form of therapy. Therapeutic care/management, level III.

Cyclodiode photocoagulation for refractory glaucoma after penetrating keratoplasty.

PubMed

Shah, P; Lee, G A; Kirwan, J K; Bunce, C; Bloom, P A; Ficker, L A; Khaw, P T

2001-11-01

This study analyzes the results of intraocular pressure (IOP) reduction by contact diode cycloablation (cyclodiode) in cases of refractory glaucoma after penetrating keratoplasty. Retrospective noncomparative, interventional case series. Twenty-eight eyes in 28 patients attending the Moorfields Eye Hospital. Cyclodiode (40 applications x 1.5 W x 1.5 seconds over 270-300 degrees ) was used to control the IOP in refractory glaucoma after penetrating keratoplasty. Postoperative IOP, graft status, visual acuity, and number of antiglaucoma medications were recorded after cyclodiode treatment. Cyclodiode resulted in a reduction of IOP from a median of 33 mmHg (interquartile range [28, 40.5]) to a median of 15 mmHg (interquartile range [12, 20.5]). Most patients had a significant lowering in IOP with a median reduction of 16 mmHg (interquartile range [12, 25]; P < 0.0001). IOPs of 6 to 21 mmHg were achieved in 22 patients (79%). Sixteen patients (57%) required more than one treatment with cyclodiode to control the IOP, with three patients (11%) requiring three treatments and two patients (7%) requiring four treatments. Visual acuity improved (> two Snellen lines of acuity) in three patients (11%) and remained the same (+/- one Snellen line) in 17 patients (61%). The mean number of antiglaucoma medications before cycloablation was 2.6 and was 1.8 after treatment (P < 0.001). Of the 19 patients (68%) with originally clear grafts, three grafts (16%) developed opacification. One patient (4%), with a history of nanophthalmos and recurrent uveal effusion, had delayed hypotony (IOP < 6 mmHg) occurring 46 months after the diode treatment. All patients had at least 6 months follow-up. These patients have often undergone multiple previous complicated ocular interventions and are often not suitable for filtration surgery. Reduction of IOP with maintenance of visual acuity and a good safety profile was achieved in most patients in this study but may require multiple treatments. We propose cyclodiode as an effective treatment for many patients in the management of refractory glaucoma after penetrating keratoplasty.

Home-based drainage of refractory ascites by a permanent-tunneled peritoneal catheter can safely replace large-volume paracentesis.

PubMed

Solbach, Philipp; Höner Zu Siederdissen, Christoph; Taubert, Richard; Ziegert, Szilvia; Port, Kerstin; Schneider, Andrea; Hueper, Katja; Manns, Michael P; Wedemeyer, Heiner; Jaeckel, Elmar

2017-05-01

Refractory ascites has a poor prognosis. Recurrent large-volume paracentesis is the current standard of care; however, it results in circulatory dysfunction and renal dysfunction, and hospitalization is commonly required. Transjugular intrahepatic portosystemic shunt placement is not an option in a substantial number of patients because of contraindications. The placement of a tunneled peritoneal drainage catheter has been shown to be effective in patients with malignant ascites. However, data in patients with nonmalignant refractory ascites are rare. We followed 24 consecutive patients in whom tunneled peritoneal drainage catheters were placed in the Endoscopy Unit at Hannover Medical School between June 2013 and December 2014. Catheters were placed in 24 patients with refractory ascites in end-stage liver disease and with a contraindication to transjugular intrahepatic portosystemic shunt placement. Placement was technically successful in all patients. The dosage of diuretics could be reduced significantly. The number of paracentesis decreased from 2.2±1 to 0 per week, although the volume of daily ascites removal remained stable (2 l). Despite frequent drainage of ascites, kidney function, serum sodium, and serum albumin remained stable. Seven adverse events occurred in six (25%) patients. Five patients listed for liver transplantation underwent successful transplantation without a negative impact. The tunneled peritoneal drainage catheter placement is a viable and effective treatment alternative in patients with refractory ascites because of end-stage liver disease, reducing diuretic intake and the need for paracentesis. The procedure avoids hyponatremia, worsening kidney function, and albumin infusions without an increased risk of spontaneous bacterial peritonitis.

Radiological Insertion of Denver Peritoneovenous Shunts for Malignant Refractory Ascites: A Retrospective Multicenter Study (JIVROSG-0809)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugawara, Shunsuke, E-mail: suga_shun@hotmail.com; Sone, Miyuki; Arai, Yasuaki

Purpose: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites. Methods: A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data. Results: PVSs were successfully placed in allmore » patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor. Conclusions: Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS.« less

Propofol Infusion Syndrome in Refractory Status Epilepticus

PubMed Central

Hwang, Woo Sub; Gwak, Hye Min; Seo, Dae-Won

2013-01-01

Background and Purpose: Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus. Methods: This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups. Results: There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O. Conclusions: RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE. PMID:24649467

Anthropometric Indices in Children With Refractory Epilepsy.

PubMed

Aminzadeh, Vahid; Dalili, Setila; Ashoorian, Yalda; Kohmanaee, Shahin; Hassanzadeh Rad, Afagh

2016-01-01

We aimed to assess the effect of body mass index (BMI) on reducing the risk of refractory seizure due to lipoid tissue factors. This matched case-control study, consisted of cases (Patients with refractory epilepsy) and controls (Healthy children) referred to 17 Shahrivar Hospital, Guilan University of Medical Sciences, Guilan, Iran during 2013-2014. Data were gathered by a form including demographic characteristics, type of epilepsy, predominant time of epilepsy, therapeutic approach, frequency of epilepsy, time of disease onset and anthropometric indices. We measured anthropometric indices and transformed them into Z-scores. Data were reported by descriptive statistics (mean and standard deviation) and analyzed by Pearson correlation coefficient, paired t test and multinomial regression analysis test using SPSS 19. There was no significant difference between sex groups regarding anthropometric indices. Generalized and focal types of epilepsies were noted on 57.5% and 38.75% of patients, respectively. Daytime epilepsies happened in 46.25% of patients and 33.75% noted no predominant time for epilepsies. Clinicians indicated poly-therapy for the majority of patients (92.5%). The most common onset times for epilepsies were 36-72 months for 32.5% of patients. Lower onset time indicated lower frequency of refractory epilepsies. Although, there was significant difference between Zheight and predominant time of epilepsies but no significant relation was found between types of epilepsies and frequency of epilepsies with anthropometric indices. Using multivariate regression analysis by backward LR, Zweight and birth weight were noted as the predicting factors of refractory epilepsies. This effect may be because of leptin. Therefore, researchers recommend further investigations regarding this issue in children with epilepsy.

The health-related quality of life of children with refractory epilepsy: a comparison of those with and without intellectual disability.

PubMed

Sabaz, M; Cairns, D R; Lawson, J A; Bleasel, A F; Bye, A M

2001-05-01

To determine whether refractory epilepsy affects the health-related quality of life (HRQOL) of children with or without intellectual disability (ID), and if the presence of ID independently compromises HRQOL in children with refractory epilepsy. Subjects were parents of children with refractory epilepsy, whose syndrome had been defined using ILAE (International League Against Epilepsy) criteria and video-EEG monitoring. Children had the presence or absence of ID determined by formal neuropsychological or educational assessment. The relative effect of epilepsy on the two intellectual ability groups was determined using relevant clinical variables. Parents completed a valid epilepsy-specific HRQOL questionnaire for children, the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), and, depending on intellectual ability level, the Child Behaviour Checklist or Developmental Behaviour Checklist. Both intellectually normal children with epilepsy and children with epilepsy and ID were more likely to have psychosocial problems compared with their respective intellectual ability reference populations. The results also revealed that children with ID had reduced HRQOL compared with intellectually normal children; a result independent of epilepsy. Analysis of the relationship between epilepsy variables and HRQOL revealed that the QOLCE was the most sensitive in detecting variation in age at onset, seizure frequency, and medications taken. The HRQOL of children with refractory epilepsy is greatly affected, regardless of intellectual ability level. The presence of ID in children with epilepsy independently depresses HRQOL outcomes. Compared with two generic HRQOL measures, the QOLCE was the most sensitive measure to variation in epilepsy variables.

SU-F-T-647: Linac-Based Stereotactic Radiosurgery (SRS) in the Treatment of Trigeminal Neuralgia: Detailed Description of SRS Procedural Technique and Reported Clinical Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

Purpose: SRS is an effective non-invasive alternative treatment modality with minimal-toxicity used to treat patients with medically/surgically refractory trigeminal neuralgia root(TNR) or those who may not tolerate surgical intervention. We present our linac-based SRS procedure for TNR treatment and simultaneously report our clinical outcomes. Methods: Twenty-eight TNR-patients treated with frame-based SRS at our institution (2009–2015) with a single-fraction point-dose of 60-80Gy to TNR were included in this IRB-approved study. Experienced neurosurgeon and radiation oncologist delineated the TNR on 1.0mm thin 3D-FIESTA-MRI that was co-registered with 0.7mm thin planning-CT. Treatment plans were generated in iPlan (BrainLAB) with a 4-mm diameter conemore » using 79 arcs with differential-weighting for Novalis-TX 6MV-SRS(1000MU/min) beam and optimized to minimize brainstem dose. Winston-Lutz test was performed before each treatment delivery with sub-millimeter isocenter accuracy. Quality assurance of frame placement was maintained by helmet-bobble-measurement before simulation-CT and before patient setup at treatment couch. OBI-CBCT scan was performed for patient setup verification without applying shifts. On clinical follow up, treatment response was assessed using Barrow Neurological Institute Pain Intensity Score(BNI-score:I–V). Results: 26/28 TNR-patients (16-males/10-females) who were treated with following single-fraction point-dose to isocenter: 80Gy(n=22),75Gy(n=1),70Gy(n=2) and 60Gy(n=1, re-treatment) were followed up. Median follow-up interval was 8.5-months (ranged:1–48.5months). Median age was 70-yr (ranged:43–93-yr). Right/left TNR ratio was 15/11. Delivered total # of average MUs was 19034±1204. Average beam-on-time: 19.0±1.3min. Brainstem max-dose and dose to 0.5cc were 13.3±2.4Gy (ranged:8.1–16.5Gy) and 3.6±0.4Gy (ranged:3.0–4.9Gy). On average, max-dose to optic-apparatus was ≤1.2Gy. Mean value of max-dose to eyes/lens was 0.26Gy/0.11Gy. Overall, 20-patients (77%) responded to treatment: 5(19%) achieved complete pain relief without medication (BNI score: I); 5(19%) had no-pain, decreased medication (BNI-score:II); 2(7.7%) had no-pain, but, continued medication (BNI-score:IIIA), and 8(30.8%) had pain that was well controlled by medication (BNI-score: IIIB). Six-patients (23.0%) did not respond to treatment (BNI-score:IV–V). Neither cranial nerve deficit nor radio-necrosis of temporal lobe was clinically observed. Conclusion: Linac-based SRS for medically/surgically refractory TNR provided an effective treatment option for pain resolution/control with very minimal if any normal tissue toxicity. Longer follow up of these patients is anticipated/needed to confirm our observations.« less

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

Absence of gender effect on amygdala volume in temporal lobe epilepsy.

PubMed

Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

2010-11-01

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. Copyright © 2010 Elsevier Inc. All rights reserved.

Experimental evidence for an effect of early-diagenetic interaction between labile and refractory marine sedimentary organic matter on nitrogen dynamics

NASA Astrophysics Data System (ADS)

Turnewitsch, Robert; Domeyer, Bettina; Graf, Gerhard

2007-05-01

In most natural sedimentary systems labile and refractory organic material (OM) occur concomitantly. Little, however, is known on how different kinds of OM interact and how such interactions affect early diagenesis in sediments. In a simple sediment experiment, we investigated how interactions of OM substrates of different degradability affect benthic nitrogen (N) dynamics. Temporal evolution of a set of selected biogeochemical parameters was monitored in sandy sediment over 116 days in three experimental set-ups spiked with labile OM (tissue of Mytilus edulis), refractory OM (mostly aged Zostera marina and macroalgae), and a 1:1 mixture of labile and refractory OM. The initial amounts of particulate organic carbon (POC) were identical in the three set-ups. To check for non-linear interactions between labile and refractory OM, the evolution of the mixture system was compared with the evolution of the simple sum of the labile and refractory systems, divided by two. The sum system is the experimental control where labile and refractory OM are virtually combined but not allowed to interact. During the first 30 days there was evidence for net dissolved-inorganic-nitrogen (DIN) production followed by net DIN consumption. (Here 'DIN' is the sum of ammonium, nitrite and nitrate.) After ˜ 30 days a quasi steady state was reached. Non-linear interactions between the two types of OM were reflected by three main differences between the early-diagenetic evolutions of nitrogen dynamics of the mixture and sum (control) systems: (1) In the mixture system the phases of net DIN production and consumption commenced more rapidly and were more intense. (2) The mixture system was shifted towards a more oxidised state of DIN products [as indicated by increased (nitrite + nitrate)/(ammonium) ratios]. (3) There was some evidence that more OM, POC and particulate nitrogen were preserved in the mixture system. That is, in the mixture system more particulate OM was preserved while a higher proportion of the decomposed particulate N was converted into inorganic N. It can be concluded that during the first days and weeks of early diagenesis the magnitude and composition of the flux of decompositional dissolved N-compounds from sediments into the overlying water was influenced by non-linear interactions of OM substrates of different degradability. Given these experimental results it is likely that the relative spatial distributions of OM of differing degradability in sediments control the magnitude and composition of the return flux of dissolved N-bearing compounds from sediments into the overlying water column.

Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes

PubMed Central

Masserdotti, Giacomo; Gillotin, Sébastien; Sutor, Bernd; Drechsel, Daniela; Irmler, Martin; Jørgensen, Helle F.; Sass, Steffen; Theis, Fabian J.; Beckers, Johannes; Berninger, Benedikt; Guillemot, François; Götz, Magdalena

2015-01-01

Summary Direct lineage reprogramming induces dramatic shifts in cellular identity, employing poorly understood mechanisms. Recently, we demonstrated that expression of Neurog2 or Ascl1 in postnatal mouse astrocytes generates glutamatergic or GABAergic neurons. Here, we take advantage of this model to study dynamics of neuronal cell fate acquisition at the transcriptional level. We found that Neurog2 and Ascl1 rapidly elicited distinct neurogenic programs with only a small subset of shared target genes. Within this subset, only NeuroD4 could by itself induce neuronal reprogramming in both mouse and human astrocytes, while co-expression with Insm1 was required for glutamatergic maturation. Cultured astrocytes gradually became refractory to reprogramming, in part by the repressor REST preventing Neurog2 from binding to the NeuroD4 promoter. Notably, in astrocytes refractory to Neurog2 activation, the underlying neurogenic program remained amenable to reprogramming by exogenous NeuroD4. Our findings support a model of temporal hierarchy for cell fate change during neuronal reprogramming. PMID:26119235

Timing Actions to Avoid Refractoriness: A Simple Solution for Streaming Sensory Signals

PubMed Central

Nogueira, Javier; Caputi, Ángel Ariel

2011-01-01

Segmenting self- from allo-generated signals is crucial for active sensory processing. We report a dynamic filter used by South American pulse electric fish to distinguish active electro-sensory signals carried by their own electric discharges from other concomitant electrical stimuli (i.e. communication signals). The filter has a sensory component, consisting of an onset type central electro-sensory neuron, and a motor component, consisting of a change in the fish's discharge rate when allo-generated electrical events occur in temporal proximity to the fish's own discharge. We investigated the sensory component of the filter by in vitro mimicking synaptic inputs occurring during behavioral responses to allo-generated interfering signals. We found that active control of the discharge enhances self-generated over allo-generated responses by forcing allo-generated signals into a central refractory period. This hypothesis was confirmed by field potential recordings in freely discharging fish. Similar sensory-motor mechanisms may also contribute to signal segmentation in other sensory systems. PMID:21789228

Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure.

PubMed

Patarroyo, Maria; Wehbe, Edgard; Hanna, Mazen; Taylor, David O; Starling, Randall C; Demirjian, Sevag; Tang, W H Wilson

2012-11-06

The purpose of this study was to examine the clinical outcomes of using slow continuous ultrafiltration (SCUF) in patients with acute decompensated heart failure (HF) refractory to intensive medical therapy. Several studies have demonstrated the clinical usefulness of early SCUF in patients with acute decompensated HF to improve fluid overload and hemodynamics. We reviewed clinical data from 63 consecutive adult patients with acute decompensated HF admitted to the Heart Failure Intensive Care Unit from 2004 through 2009 who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. The mean creatinine level was 1.9 ± 0.8 mg/dl on admission and 2.2 ± 0.9 mg/dl at SCUF initiation. After 48 hours of SCUF, there were significant improvements in hemodynamic variables (mean pulmonary arterial pressure: 40 ± 12 mm Hg vs. 33 ± 8 mm Hg, p = 0.002, central venous pressure: 20 ± 6 mm Hg vs. 16 ± 8 mm Hg, p = 0.007, mean pulmonary wedge pressure: 27 ± 8 mm Hg vs. 20 ± 7 mm Hg, p = 0.02, Fick cardiac index: 2.2 l/min/m(2) [interquartile range: 1.87 to 2.77 l/min/m(2)] vs. 2.6 l/min/m(2) [interquartile range: 2.2 to 2.9 l/min/m(2)], p = 0.0008), and weight loss (102 ± 25 kg vs. 99 ± 23 kg, p < 0.0001). However, there were no significant improvements in serum creatinine levels (2.2 ± 0.9 mg/dl vs. 2.4 ± 1 mg/dl, p = 0.12) and blood urea nitrogen (60 ± 30 mg/dl vs. 60 ± 28 mg/dl, p = 0.97). Fifty-nine percent required conversion to continuous hemodialysis during their hospital course, and 14% were dependent on dialysis at hospital discharge. Thirty percent died during hospitalization, and 6 patients were discharged to hospice care. In our single-center experience, SCUF after admission for acute decompensated HF refractory to standard medical therapy was associated with high incidence of subsequent transition to renal replacement therapy and high in-hospital mortality, despite significant improvement in hemodynamics. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Developing the Pediatric Refractory Epilepsy Questionnaire: a pilot study.

PubMed

Purusothaman, Vaishnavi; Ryther, Robin C C; Bertrand, Mary; Harker, Lisa A; Jeffe, Donna B; Wallendorf, Michael; Smyth, Matthew D; Limbrick, David D

2014-08-01

Up to 14% of children with epilepsy continue to experience seizures despite having appropriate medical therapy and develop medically refractory epilepsy (MRE). Assessing clinical outcomes and therapeutic efficacy in children with MRE undergoing palliative epilepsy surgery has been challenging because of the lack of a quantitative instrument capable of estimating the clinical status of these patients. The ideal instrument would at once consider seizure control, neurodevelopment, caregiver burden, and quality of life. The purpose of this study was to develop and pilot the Pediatric Refractory Epilepsy Questionnaire (PREQ), a quantitative instrument to assess the severity and individual burden of epilepsy in children with MRE undergoing palliative epilepsy treatments. The caregivers of 25 patients with MRE completed the PREQ and the Quality of Life in Childhood Epilepsy (QOLCE) measure and participated in a semistructured interview. Medical records of the patients were reviewed, an Early Childhood Epilepsy Severity Scale (E-CHESS) score was calculated, and a Global Assessment of Severity of Epilepsy (GASE) score was obtained for each patient. The initial PREQ was modified based on the analysis of responses, association with previously validated scales, comments from caregivers, and expertise of the PREQ panelists. Pediatric Refractory Epilepsy Questionnaire subscale scores were calculated based on clinical paradigm and compared with independent measures of seizure severity and quality of life. Significant correlations were observed between the seizure severity subscale and the GASE score (r=0.55) and between the mood subscale and the well-being score (r=0.61) on the QOLCE. Significant correlations were also observed between the caregiver rating of seizure severity and the GASE score (r=0.53), the social activity score (r=0.57), and the behavior score (r=0.43) on the QOLCE. Correlations between the caregiver rating of quality of life and the quality of life score (r=0.58) and the number of AEDs used (r=0.45) were also significant. This pilot study is an initial, critical step in the development of the PREQ. The significant correlations between the PREQ subscales and the external epilepsy severity and quality of life measures lend preliminary support to our hypothesis that the PREQ is assessing the severity of epilepsy along with other important domains, such as mood, neurodevelopment, and quality of life. A larger prospective study of this modified PREQ is currently underway to further develop the PREQ. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of Convulsive Status Epilepticus.

PubMed

Grover, Eric H; Nazzal, Yara; Hirsch, Lawrence J

2016-03-01

Convulsive status epilepticus (CSE) is a medical emergency with an associated high mortality and morbidity. It is defined as a convulsive seizure lasting more than 5 min or consecutive seizures without recovery of consciousness. Successful management of CSE depends on rapid administration of adequate doses of anti-epileptic drugs (AEDs). The exact choice of AED is less important than rapid treatment and early consideration of reversible etiologies. Current guidelines recommend the use of benzodiazepines (BNZ) as first-line treatment in CSE. Midazolam is effective and safe in the pre-hospital or home setting when administered intramuscularly (best evidence), buccally, or nasally (the latter two possibly faster acting than intramuscular (IM) but with lower levels of evidence). Regular use of home rescue medications such as nasal/buccal midazolam by patients and caregivers for prolonged seizures and seizure clusters may prevent SE, prevent emergency room visits, improve quality of life, and lower health care costs. Traditionally, phenytoin is the preferred second-line agent in treating CSE, but it is limited by hypotension, potential arrhythmias, allergies, drug interactions, and problems from extravasation. Intravenous valproate is an effective and safe alternative to phenytoin. Valproate is loaded intravenously rapidly and more safely than phenytoin, has broad-spectrum efficacy, and fewer acute side effects. Levetiracetam and lacosamide are well tolerated intravenous (IV) AEDs with fewer interactions, allergies, and contraindications, making them potentially attractive as second- or third-line agents in treating CSE. However, data are limited on their efficacy in CSE. Ketamine is probably effective in treating refractory CSE (RCSE), and may warrant earlier use; this requires further study. CSE should be treated aggressively and quickly, with confirmation of treatment success with epileptiform electroencephalographic (EEG), as a transition to non-convulsive status epilepticus is common. If the patient is not fully awake, EEG should be continued for at least 24 h. How aggressively to treat refractory non-convulsive SE (NCSE) or intermittent non-convulsive seizures is less clear and requires additional study. Refractory SE (RSE) usually requires anesthetic doses of anti-seizure medications. If an auto-immune or paraneoplastic etiology is suspected or no etiology can be identified (as with cryptogenic new onset refractory status epilepticus, known as NORSE), early treatment with immuno-modulatory agents is now recommended by many experts.

Emerging therapeutic options in GERD.

PubMed

Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

2013-06-01

Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Supra-recommendation Treatment of Super-refractory Status Epilepticus.

PubMed

Vyas, Devashish Dhiren; Dash, Gopal Krishna

2016-06-01

A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India.

Immune deficiency in chronic rhinosinusitis: screening and treatment

PubMed Central

Chiarella, Sergio E.; Grammer, Leslie C.

2017-01-01

Introduction Chronic rhinosinusitis (CRS) is a prevalent disease with a high annual cost of treatment. Immune deficiencies are more common in individuals with CRS and should be especially considered in those patients who are refractory to medical and surgical therapy. Areas covered We performed a literature search in PubMed of the terms “immunodeficiency” and “sinusitis” or “rhinosinusitis” from 2006 through March 2016. All abstracts were reviewed to determine if they pertained to human disease; relevant articles were evaluated in their entirety and included in this review. Expert commentary CRS is a common disease; in those patients with frequent exacerbations or who are refractory to treatment, an immunodeficiency evaluation should be considered. Treatment includes vaccination, antibiotic therapy, immunoglobulin replacement and surgery. PMID:27500811

Time as a dimension of medical law.

PubMed

Harrington, John

2012-01-01

This paper considers the importance of temporal categories in medical law argumentation. Proceeding from a view of time as plural, rhetorical, and socially produced, it argues that decision making in areas such as the access of minors to contraception, abortion law, end of life care, and emergency caesarian sections can be usefully read as struggles over appropriate time frames. Judges, legislators, and commentators seek to establish the plausibility of a given legal development with reference to the common sense understanding of time which it embodies. Such understandings may be plausible because of their resonance with the diverse temporalities of the law itself. Alternatively, they may reproduce the temporal frames proper to medical science. Not only is time represented in medical law rhetoric, but deliberation in such cases is also subject to temporal pressures which may significantly affect their outcome. The paper concludes by considering the broader political stakes of intertemporal struggles in medical law.

Comparative randomized study on the efficaciousness of treatment of BOO due to BPH in patients with prostate up to 100 gr by endoscopic gyrus prostate resection versus open prostatectomy. Preliminary data.

PubMed

Giulianelli, Roberto; Brunori, Stefano; Gentile, Barbara Cristina; Vincenti, Giorgio; Nardoni, Stefano; Pisanti, Francesco; Shestani, Teuta; Mavilla, Luca; Albanesi, Luca; Attisani, Francesco; Mirabile, Gabriella; Schettini, Manlio

2011-06-01

With the advent of medical management and minimally techniques for benign prostate hypeplasia (BPH), invasive surgical procedures such open prostatectomy (OPSU) have become less common, although selected patients may still benefit from open prostatectomy. Aim of this study was to evaluate efficacy and safety of Bipolar TURP (Gyrus electro surgical system) versus standard open prostatectomy in patients with lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy. From January 2003 to January 2004, 140 patients affected by mild-severe LUTS, secondary to BOO from BPH, refractory to medical therapy, with markedly enlarged glands, were randomized in two groups (1:1), and subjected to open prostatectomy (OPSU) carried out with traditional method (Bracci Thechnique) versus transurethral resection of the prostate (TURP) utilizing the bipolar methodology. Preoperative work-up included IPSS, IIEF-5 and Qol questionnaires. All patients were submitted to uroflowmetry, transrectal ultrasound (TRUS), measurament of postvoidal residual urine and PSA determination. IPSS, IIEF-5 and Qol, uroflowmetry, TRUS, measurement of post-voidal residual urine, PSA determination and number of reoperations were evaluated at 1, 3, 6, 12, 18, 24, 30 and 36 months. Operative time, resected tissue weight and perioperative complications were also registered. Total post-operative catheter time, total postoperative hospital stay, haemoglobin loss were recorded in the 2 groups. Comparative data on IPSS symptom score, IIEF-5 and Qol, PSA, peak urinary flow rates and post-void residual urine volume in the 2 groups were similar but showed a significative improvement with respect to baseline value. Postoperative haemoglobin levels, postoperative catheterization, hospital stay and 3-yr overall surgical re-treatment-free rate were significantly better in the Bipolar group. In the treatment of LUTS due to bladder outlet obstruction (BOO) with markedly enlarged glands refractory to medical therapy, Bipolar TURP has a comparable outcome to open prostatectomy at short and medium term according to both subjective and objective outcome measures.

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

PubMed Central

Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

2015-01-01

Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment. PMID:25962114

Palliative sedation for intolerable suffering.

PubMed

Maltoni, Marco; Scarpi, Emanuela; Nanni, Oriana

2014-07-01

The purpose of this review is to provide an update on palliative sedation in palliative and end-of-life care. Palliative sedation is the medical procedure used to deal with refractory symptoms in advanced cancer patients when all other specific approaches have failed. Palliative sedation, in the strictest sense of the term, is a proportionate (proportionate palliative sedation, PPS) and intrinsically variable procedure used on an individual basis to relieve refractory symptoms in terminally ill patients, without the intention of hastening death. Completely separate from any other end-of-life decision and not intended to hasten death, palliative sedation has been shown not to have a detrimental impact on survival. To maintain palliative sedation as a legitimate clinical procedure from any ethical or clinical point of view, it must be limited to the restricted area for which it was conceived, that is, relief from refractory suffering as deemed necessary by a patient and by an experienced palliative care team. In this way, there is no risk of associating palliative sedation with other end-of-life decisions. Close collaboration is needed between oncologists and palliative care physicians for this clinical procedure.

Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

PubMed

Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S

2012-09-01

Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

ClinicalTrials.gov

2018-04-23

Neuroblastoma; Rhabdomyosarcoma; Ewing's Sarcoma; Ewing's Tumor; Sarcoma, Ewing's; Sarcomas, Epitheliod; Sarcoma, Soft Tissue; Sarcoma, Spindle Cell; Melanoma; Malignant Melanoma; Clinical Oncology; Oncology, Medical; Pediatrics, Osteosarcoma; Osteogenic Sarcoma; Osteosarcoma Tumor; Sarcoma, Osteogenic; Tumors; Cancer; Neoplasia; Neoplasm; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

Management of Status Epilepticus in Children

PubMed Central

Smith, Douglas M.; McGinnis, Emily L.; Walleigh, Diana J.; Abend, Nicholas S.

2016-01-01

Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children. PMID:27089373

75 FR 4407 - The Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... premarket approval application for the Deep Brain Stimulation System for Epilepsy sponsored by Medtronic...-onset seizures (affecting only a part of the brain when they begin), with or without secondary... a partial-onset seizure that later spreads to the whole brain. ``Refractory'' to antiepileptic...

Eye Disorders in Old People

PubMed Central

M., Khalaj; A., Barikani; H., Ghasemi

2013-01-01

Background: Visual impairment is one of a major public health problem among elderly people. Object: Aim of this study was determining the prevalence of visual impairment in median and old peoples in Qazvin (Iran). Method: In this cross sectional study, with a simple random sampling, 446 patients older than 5o years who were referred to outpatient ophthalmology clinics at Avecina hospital of Qazvin (a province of Iran) in 2010 were enrolled. Participants first complete a questionnaire with 25 questions toward demographic and past medical history and then were examined by ophthalmologist. These examinations includes direct and indirect ophthalmoscopy, slit lamp examination, measurement of uncorrected visual acuity and visual acuity with current glasses, lensometery of the previous glasses, refraction with and without the use of cycloplegic and determining the best corrected visual acuity. All slit lamp examinations were performed by the same ophthalmologist. Data were analyzed with SPSS16 with use of Chi – Square test with Pvalue <0.05. Results: In this study 446 patients were examined that 54.7% were male. Mean age of study population was 62+-9.3 years old. 96.4% of participants had refractory disorder. Prevalence of myopia, hyperopia and astigmatism were 33.6%, 45.9% and 16.8% respectively. Of patients 17.4% had diabetes. Of participants 28.9% had temporal headache, 37% red eye, 41.2% flashing, 27.3% and 28% had dryness and discharge of eye respectively. 31.1% of participants had eyelide problem, 4.7% Color Vision Deficiency (CVD) and 3.8% had family history of CVD. Of total 4.5% had glaucoma, 3.3% macular degeneration and 21.7% had hypertension. 0.6% of population had macular degeneration, 0.4% of population had glaucoma Of 892 eyes (446 individuals), 36.2% had visual acuity less than 7/10, 1.7% light perception (LP) and 0.22% no light perception (NLP) and 2.7% finger count. Conclusion: Refractory errors, cataract and amblyopia were most important eye disorders in older people in Qazvin. PMID:23283039

Demyelination of vestibular nerve axons in unilateral Ménière's disease.

PubMed

Spencer, Robert F; Sismanis, Aristides; Kilpatrick, Jefferson K; Shaia, Wayne T

2002-11-01

We conducted a study to determine whether vestibular nerves in patients with unilateral Ménière's disease whose symptoms are refractory to medical management exhibit neuropathologic changes. We also endeavored to determine whether retrocochlear abnormalities are primary or secondary factors in the disease process. To these ends, we obtained vestibular nerve segments from five patients during retrosigmoid (posterior fossa) neurectomy, immediately fixed them, and processed them for light and electron microscopy. We found that all five segments exhibited moderate to severe demyelination with axonal sparing. Moreover, we noted that reactive astrocytes produced an extensive proliferation of fibrous processes and that the microglia assumed a phagocytic role. We conclude that the possible etiologies of demyelination include viral and/or immune-mediated factors similar to those seen in other demyelinating diseases, such as multiple sclerosis and Guillain-Barré syndrome. Our findings suggest that some forms of Ménière's disease that are refractory to traditional medical management might be the result of retrocochlear pathology that affects the neuroglial portion of the vestibular nerve.

Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

PubMed

Segar, David J; Chodakiewitz, Yosef G; Torabi, Radmehr; Cosgrove, G Rees

2015-06-01

Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

Transcutaneous stimulation of the posterior tibial nerve for treating refractory urge incontinence of idiopathic and neurogenic origin.

PubMed

Valles-Antuña, C; Pérez-Haro, M L; González-Ruiz de L, C; Quintás-Blanco, A; Tamargo-Diaz, E M; García-Rodríguez, J; San Martín-Blanco, A; Fernandez-Gomez, J M

2017-09-01

To assess the efficacy of treatment with transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with urge urinary incontinence, of neurogenic or nonneurogenic origin, refractory to first-line therapeutic options. We included 65 patients with urge urinary incontinence refractory to medical treatment. A case history review, a urodynamic study and a somatosensory evoked potentials (SEP) study were conducted before the TPTNS, studying the functional urological condition by means of a voiding diary. The treatment consisted of 10 weekly sessions of TPTNS lasting 30minutes. Some 57.7% of the patients showed abnormal tibial SEPs, and 42% showed abnormal pudendal SEPs. A statistically significant symptomatic improvement was observed in all clinical parameters after treatment with TPTNS, and 66% of the patients showed an overall improvement, regardless of sex, the presence of underlying neurological disorders, detrusor hyperactivity in the urodynamic study or SEP disorders. There were no adverse effects during the treatment. TPTNS is an effective and well tolerated treatment in patients with urge incontinence refractory to first-line therapies and should be offered early in the treatment strategy. New studies are needed to identify the optimal parameters of stimulation, the most effective treatment protocols and long-term efficacy, as well as its applicability to patients with a neurogenic substrate. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

CSF Lumbar Drainage: A Safe Surgical Option in Refractory Intracranial Hypertension Associated with Acute Posttraumatic External Hydrocephalus.

PubMed

Manet, R; Schmidt, E A; Vassal, F; Charier, D; Gergelé, L

2016-01-01

External lumbar drainage (ELD) of cerebrospinal fluid (CSF) in posttraumatic refractory intracranial hypertension (ICHT) is controversial. We report our experience of ELD in ICHT associated with acute disturbance of CSF flow within subarachnoid spaces (SASs). Four adult patients admitted to the neurointensive care unit for severe TBI who presented with secondary ICHT are retrospectively reported. When refractory to second-tier therapy, if external ventricular drainage were not possible or failed, and in the absence of an indication for craniotomy to treat a mass lesion or decompressive craniectomy, we assessed the evolution of CSF volume within cranial SAS and checked the presence of basal cisterns and the absence of tonsillar herniation to evaluate interest in and the safety of ELD. As second-tier therapy failed to lower intracranial pressure (ICP; mean ICP 37 ± 5 mmHg), and computed tomography (CT) showed abnormally enlarged cranial SAS following traumatic subarachnoid hemorrhage, patients received ELD. ICP decreased, with immediate and long-term effect (mean ICP 5 mmHg ± 2 mmHg). There were no complications to report. Acute traumatic external hydrocephalus may explain some of the specific situations of secondary increased ICP, with a "normal" CT scan, that is refractory to medical treatment. In these situations, lumbar drainage should be considered to be a safe, minimally invasive, and effective surgical option.

The efficacy of Ahmed glaucoma valve drainage devices in cases of adult refractory glaucoma in Indian eyes

PubMed Central

Parihar, Jitendra K S; Vats, Devendra P; Maggon, Rakesh; Mathur, Vijay; Singh, Anirudh; Mishra, Sanjay K

2009-01-01

Aim: To evaluate the efficacy of Ahmed glaucoma valve (AGV) drainage devices in cases of adult refractory glaucoma in Indian eyes. Settings and Design: Retrospective interventional case series study. Materials and Methods: Fifty two eyes of 32 patients of refractory glaucoma in the age group of 35 to 60 years who underwent AGV implantation with or without concomitant procedures from January 2003 to Jan 2007 were studied. Of these, 46 eyes (88%) had undergone filtering surgery earlier whereas remaining eyes underwent primary AGV implantation following failure of maximal medical therapy. The follow up ranged between 12 months to 48 months Results: Eighteen eyes (35%) had undergone phacoemulsification with AGV implantation, penetrating keratoplasty (PK) with AGV and intraocular lens (IOL) implantation in 13 eyes (25%), AGV over preexisting IOL in eight eyes (15%). AGV implantation alone was done in six (11%) eyes. Anterior chamber (AC) reconstruction with secondary IOL and AGV was performed in the remaining eyes. The mean intra ocular pressure (IOP) decreased from 36.3 ± 15.7 mm Hg to 19.6 ± 9.2 mm Hg. Complete success as per criteria was achieved in 46 eyes (88%). None of the eyes had failure to maintain IOP control following AGV. Conclusion: The AGV resulted in effective and sustained control of IOP in cases of adult refractory glaucoma in intermediate follow up. PMID:19700871

Application of a temporal reasoning framework tool in analysis of medical device adverse events.

PubMed

Clark, Kimberly K; Sharma, Deepak K; Chute, Christopher G; Tao, Cui

2011-01-01

The Clinical Narrative Temporal Relation Ontology (CNTRO)1 project offers a semantic-web based reasoning framework, which represents temporal events and relationships within clinical narrative texts, and infer new knowledge over them. In this paper, the CNTRO reasoning framework is applied to temporal analysis of medical device adverse event files. One specific adverse event was used as a test case: late stent thrombosis. Adverse event narratives were obtained from the Food and Drug Administration's (FDA) Manufacturing and User Facility Device Experience (MAUDE) database2. 15 adverse event files in which late stent thrombosis was confirmed were randomly selected across multiple drug eluting stent devices. From these files, 81 events and 72 temporal relations were annotated. 73 temporal questions were generated, of which 65 were correctly answered by the CNTRO system. This results in an overall accuracy of 89%. This system should be pursued further to continue assessing its potential benefits in temporal analysis of medical device adverse events.

Safety and efficacy of a low-cost glaucoma drainage device for refractory childhood glaucoma.

PubMed

Kaushik, Sushmita; Kataria, Pankaj; Raj, Srishti; Pandav, Surinder Singh; Ram, Jagat

2017-12-01

To evaluate the safety and efficacy of a low-cost glaucoma drainage device (GDD), Aurolab aqueous drainage implant (AADI), similar in design to the Baerveldt glaucoma implant (BGI), in refractory childhood glaucoma. This prospective interventional study was conducted in a tertiary care postgraduate teaching institute. Children aged <16 years with uncontrolled intraocular pressure (IOP) refractory to medical treatment and considered at high risk of failure following trabeculectomy were recruited. Eligible children were implanted with the AADI. Those completing minimum 6-month follow-up were included. Main outcome measures were IOP reduction from preoperative values and postoperative complications. 34 eyes of 31 patients were analysed. Average follow-up was 18.3±6.9 months. Mean IOP reduced from 27.4±7.5 mm Hg on maximum medication to 14.6±10.74 mm Hg, 13.8±7.5 mm Hg, 12.8±5.6 mm Hg and 14.7±5.8 mm Hg at 1 week, 6 months, 1 year (32 eyes of 29 children) and 2 years (25 eyes of 22 children) postoperatively, respectively (p<0.001). The cumulative probability of success was 91.18% at 6 months and 81.7% at 18-24 months. Mean number of topical medications decreased from 3.1±0.6 to 1.8±1.3 at 6 months and 1.6±1.1 at 24 months (p<0.001). Preoperatively, 25 patients required systemic acetazolamide, decreasing to three patients at 2 years. There was no tube erosion or infection. One eye developed retinal detachment. The AADI appears to be a viable low-cost GDD with effectiveness and safety profile comparable with published reports of the BGI and Ahmed glaucoma valve implant in children. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Long-term results of Ahmed glaucoma valve implantation in Egyptian population

PubMed Central

Elhefney, Eman; Mokbel, Tharwat; Abou Samra, Waleed; Kishk, Hanem; Mohsen, Tarek; El-Kannishy, Amr

2018-01-01

AIM To evaluate the long-term results and complications of Ahmed glaucoma valve (AGV) implantation in a cohort of Egyptian patients. METHODS A retrospective study of 124 eyes of 99 patients with refractory glaucoma who underwent AGV implantation and had a minimum follow-up of 5y was performed. All patients underwent complete ophthalmic examination and intraocular pressure (IOP) measurement before surgery and at 1d, weekly for the 1st month, 3, 6mo, and 1y after surgery and yearly afterward for 5y. IOP was measured by Goldmann applanation tonometry and/or Tono-Pen. Complications and the number of anti-glaucoma medications needed were recorded. Success was defined as IOP less than 21 mm Hg with or without anti-glaucoma medication and without additional glaucoma surgery. RESULTS Mean age was 23.1±19.9y. All eyes had at least one prior glaucoma surgery. IOP was reduced from a mean of 37.2±6.8 to 19.2±5.2 mm Hg after 5y follow-up with a reduced number of medications from 2.64±0.59 to 1.81±0.4. Complete and qualified success rates were 31.5% and 46.0% respectively at the end of follow-up. The most common complications were encapsulated cyst formation in 51 eyes (41.1%), complicated cataract in 9 eyes (7.25%), recessed tube in 8 eyes (6.45%), tube exposure in 6 eyes (4.8%) and corneal touch in 6 eyes (4.8%). Other complications included extruded AGV, endophthalmitis and persistent hypotony. Each of them was recorded in only 2 eyes (1.6%). CONCLUSION Although refractory glaucoma is a difficult problem to manage, AGV is effective and relatively safe procedure in treating refractory glaucoma in Egyptian patients with long-term follow-up. Encapsulated cyst formation was the most common complication, which limits successful IOP control after AGV implantation. However, effective complications management can improve the rate of success. PMID:29600175

Long-term results of Ahmed glaucoma valve implantation in Egyptian population.

PubMed

Elhefney, Eman; Mokbel, Tharwat; Abou Samra, Waleed; Kishk, Hanem; Mohsen, Tarek; El-Kannishy, Amr

2018-01-01

To evaluate the long-term results and complications of Ahmed glaucoma valve (AGV) implantation in a cohort of Egyptian patients. A retrospective study of 124 eyes of 99 patients with refractory glaucoma who underwent AGV implantation and had a minimum follow-up of 5y was performed. All patients underwent complete ophthalmic examination and intraocular pressure (IOP) measurement before surgery and at 1d, weekly for the 1 st month, 3, 6mo, and 1y after surgery and yearly afterward for 5y. IOP was measured by Goldmann applanation tonometry and/or Tono-Pen. Complications and the number of anti-glaucoma medications needed were recorded. Success was defined as IOP less than 21 mm Hg with or without anti-glaucoma medication and without additional glaucoma surgery. Mean age was 23.1±19.9y. All eyes had at least one prior glaucoma surgery. IOP was reduced from a mean of 37.2±6.8 to 19.2±5.2 mm Hg after 5y follow-up with a reduced number of medications from 2.64±0.59 to 1.81±0.4. Complete and qualified success rates were 31.5% and 46.0% respectively at the end of follow-up. The most common complications were encapsulated cyst formation in 51 eyes (41.1%), complicated cataract in 9 eyes (7.25%), recessed tube in 8 eyes (6.45%), tube exposure in 6 eyes (4.8%) and corneal touch in 6 eyes (4.8%). Other complications included extruded AGV, endophthalmitis and persistent hypotony. Each of them was recorded in only 2 eyes (1.6%). Although refractory glaucoma is a difficult problem to manage, AGV is effective and relatively safe procedure in treating refractory glaucoma in Egyptian patients with long-term follow-up. Encapsulated cyst formation was the most common complication, which limits successful IOP control after AGV implantation. However, effective complications management can improve the rate of success.

The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

PubMed

Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

2016-12-01

More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

Usefulness of cardiac biomarkers to predict cardiac recovery in patients on extracorporeal membrane oxygenation support for refractory cardiogenic shock.

PubMed

Luyt, Charles-Edouard; Landivier, Antoine; Leprince, Pascal; Bernard, Maguy; Pavie, Alain; Chastre, Jean; Combes, Alain

2012-10-01

No prognostic markers of myocardial recovery in patients with refractory cardiogenic shock requiring circulatory support are known, but early identification of patients who will not recover might provide an opportunity to change the treatment strategy to improve outcome. Because N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic markers in patients with cardiac failure, we hypothesized that, among patients with refractory cardiogenic shock of potentially reversible cause supported with extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might help identify patients who would recover. This was a prospective, observational, single-center study in a medical-surgical intensive care unit. Among 41 consecutive patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, 18 recovered and were successfully weaned off the machine. Blood N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and 7 post-ECMO. Neither the absolute values of those biomarkers at days 1, 3, or 7 nor their kinetics during the first week differed between patients weaned or not. Areas under the receiver operating characteristic curves (95% confidence interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and 0.61 (0.43-0.78), respectively. In patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, early measurements of cardiac biomarkers are not useful for identifying those who would recover. Copyright © 2012 Elsevier Inc. All rights reserved.

Bumetanide is not capable of terminating status epilepticus but enhances phenobarbital efficacy in different rat models.

PubMed

Töllner, Kathrin; Brandt, Claudia; Erker, Thomas; Löscher, Wolfgang

2015-01-05

In about 20-40% of patients, status epilepticus (SE) is refractory to standard treatment with benzodiazepines, necessitating second- and third-line treatments that are not always successful, resulting in increased mortality. Rat models of refractory SE are instrumental in studying the changes underlying refractoriness and to develop more effective treatments for this severe medical emergency. Failure of GABAergic inhibition is a likely cause of the development of benzodiazepine resistance during SE. In addition to changes in GABAA receptor expression, trafficking, and function, alterations in Cl(-) homeostasis with increased intraneuronal Cl(-) levels may be involved. Bumetanide, which reduces intraneuronal Cl(-) by inhibiting the Cl(-) intruding Na(+), K(+), Cl(-) cotransporter NKCC1, has been reported to interrupt SE induced by kainate in urethane-anesthetized rats, indicating that this diuretic drug may be an interesting candidate for treatment of refractory SE. In this study, we evaluated the effects of bumetanide in the kainate and lithium-pilocarpine models of SE as well as a model in which SE is induced by sustained electrical stimulation of the basolateral amygdala. Unexpectedly, bumetanide alone was ineffective to terminate SE in both conscious and anesthetized adult rats. However, it potentiated the anticonvulsant effect of low doses of phenobarbital, although this was only seen in part of the animals; higher doses of phenobarbital, particularly in combination with diazepam, were more effective to terminate SE than bumetanide/phenobarbital combinations. These data do not suggest that bumetanide, alone or in combination with phenobarbital, is a valuable option in the treatment of refractory SE in adult patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

PubMed

Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

2018-06-01

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

PubMed

Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

2013-09-01

Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

Long-term clinical outcomes of Ahmed valve implantation in patients with refractory glaucoma.

PubMed

Lee, Chang Kyu; Ma, Kyoung Tak; Hong, Young Jae; Kim, Chan Yun

2017-01-01

To evaluate the long-term efficacy of intraocular pressure (IOP) reduction and complications of Ahmed Glaucoma Valve (AGV) implantation in patients with refractory glaucoma. Retrospective study. The study involved 302 refractory glaucoma patients who underwent AGV implantation and had a minimum follow-up of 6 months between March 1995 and December 2013. An operation was defined as successful when (1) the postoperative IOP remained between 5 and 21 mmHg and was reduced 30% compared to the baseline IOP with or without medication, (2) there was no loss of light perception or vision-threatening severe complications, and (3) no additional filtering or aqueous drainage surgery was required. Clinical records were reviewed. IOP, anti-glaucoma medications, and complications. The mean follow-up period was 62.25 months (range, 6 to 190 months). The cumulative probability of success was 89% at 6 months, 81% at 1 year, 66% at 3 years, 44% at 10 years, and 26% at 15 years. IOP was reduced from a mean of 32.2 ± 10.5 mmHg to 18.6 ± 9.1 mmHg at 1 month, 15.2 ± 7.0 mmHg at 6 months, and 14.2 ± 3.5 mmHg at 15 years. Surgical failures were significantly increased when preoperative IOP was high, and when severe complications occurred after AGV implantation (P < 0.05). AGV implantation was successful for IOP control in patients with refractive glaucoma in the long term. However, the success rate of surgery decreased over time. Preoperative high IOP and severe complications related to the operation were significant risk factors for failure.

A case of severe refractory chronic urticaria: a novel method for evaluation and treatment.

PubMed

Otto, Hans F; Calabria, Christopher W

2009-01-01

With cholinergic urticaria (ChU), the ultimate diagnosis often depends on the demonstration of characteristic urticaria by appropriate provocation. Several treatment options may be helpful but traditional options (antihistamines, leukotriene inhibitors, and immunosuppressives) may be exhausted by the refractory ChU patient. Here, we describe such a case. Demonstration of immediate hypersensitivity to autologous sweat skin testing (ASwST) may provide a rationale for use of omalizumab (Xolair, Genentech Novartis, South San Francisco, CA). Patients with severe ChU may have difficulty producing sufficient quantities of sweat for ASwST given that the very effort that produces the sample exacerbates ChU. Generation of sweat by iontophoresis with pilocarpine nitrate can be performed at many large medical centers. The procedure is simple, safe, and produces varying amounts of sweat depending on the individual. This sweat can then be used for ASwST. Our patient had a positive ASwST with appropriate positive and negative controls. Our testing methods were validated by negative ASwST, saline control, and positive histamine control in a nonatopic, nonurticarial control patient. By the patient's second injection of omalizumab, her quality of life score was significantly improved, as were her daily medication scores and exercise tolerance. We describe the first case of a patient with severe refractory ChU who had a positive ASwST by a novel collection method who has been successfully treated with omalizumab. We present a novel tool for the evaluation and demonstration of sweat-specific IgE in ChU patients who are unable to provide sweat by more traditional means.

Systematic review of the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion for the treatment of refractory chronic cluster headache.

PubMed

Sánchez-Gómez, L M; Polo-deSantos, M; Pinel-González, A; Oreja-Guevara, C; Luengo-Matos, S

2018-01-12

This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic cluster headache. Various medical databases were used to perform a systematic review of the scientific literature. The search for articles continued until 31 October 2016, and included clinical trials, systematic reviews and/or meta-analyses, health technology assessment reports, and clinical practice guidelines that included measurements of efficiency/effectiveness or adverse effects associated with the treatment. The review excluded cohort studies, case-control studies, case series, literature reviews, letters to the editor, opinion pieces, editorials, and studies that had been duplicated or outdated by later publications from the same institution. Regarding effectiveness, we found that SPG stimulation had positive results for pain relief, attack frequency, medication use, and patients' quality of life. In the results regarding safety, we found a significant number of adverse events in the first 30 days following the intervention. Removal of the device was necessary in some patients. Little follow-up data, and no long-term data, is available. These results are promising, despite the limited evidence available. We consider it essential for research to continue into the safety and efficacy of SPG stimulation for patients with refractory chronic cluster headache. In cases where this intervention may be indicated, treatment should be closely monitored. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease: A Randomized Clinical Trial.

PubMed

Bond, Aaron E; Shah, Binit B; Huss, Diane S; Dallapiazza, Robert F; Warren, Amy; Harrison, Madaline B; Sperling, Scott A; Wang, Xin-Qun; Gwinn, Ryder; Witt, Jennie; Ro, Susie; Elias, W Jeffrey

2017-12-01

Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown. To assess safety and efficacy at 12-month follow-up, accounting for placebo response, of unilateral FUS thalamotomy for patients with TDPD. Of the 326 patients identified from an in-house database, 53 patients consented to be screened. Twenty-six were ineligible, and 27 were randomized (2:1) to FUS thalamotomy or a sham procedure at 2 centers from October18, 2012, to January 8, 2015. The most common reasons for disqualification were withdrawal (8 persons [31%]), and not being medication refractory (8 persons [31%]). Data were analyzed using intention-to-treat analysis, and assessments were double-blinded through the primary outcome. Twenty patients were randomized to unilateral FUS thalamotomy, and 7 to sham procedure. The sham group was offered open-label treatment after unblinding. The predefined primary outcomes were safety and difference in improvement between groups at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor (CRST). Secondary outcomes included descriptive results of Unified Parkinson's Disease Rating Scale (UPDRS) scores and quality of life measures. Of the 27 patients, 26 (96%) were male and the median age was 67.8 years (interquartile range [IQR], 62.1-73.8 years). On-medication median tremor scores improved 62% (IQR, 22%-79%) from a baseline of 17 points (IQR, 10.5-27.5) following FUS thalamotomy and 22% (IQR, -11% to 29%) from a baseline of 23 points (IQR, 14.0-27.0) after sham procedures; the between-group difference was significant (Wilcoxon P = .04). On-medication median UPDRS motor scores improved 8 points (IQR, 0.5-11.0) from a baseline of 23 points (IQR, 15.5-34.0) following FUS thalamotomy and 1 point (IQR, -5.0 to 9.0) from a baseline of 25 points (IQR, 15.0-33.0) after sham procedures. Early in the study, heating of the internal capsule resulted in 2 cases (8%) of mild hemiparesis, which improved and prompted monitoring of an additional axis during magnetic resonance thermometry. Other persistent adverse events were orofacial paresthesia (4 events [20%]), finger paresthesia (1 event [5%]), and ataxia (1 event [5%]). Focused ultrasound thalamotomy for patients with TDPD demonstrated improvements in medication-refractory tremor by CRST assessments, even in the setting of a placebo response. ClinicalTrials.gov identifier NCT01772693.

Reduced sensitivity of the N400 and late positive component to semantic congruity and word repetition in left temporal lobe epilepsy.

PubMed

Olichney, John M; Riggins, Brock R; Hillert, Dieter G; Nowacki, Ralph; Tecoma, Evelyn; Kutas, Marta; Iragui, Vicente J

2002-07-01

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% "congruous" (category exemplars) and 50% "incongruous" (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from approximately 10-140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

The Role of Skull Modeling in EEG Source Imaging for Patients with Refractory Temporal Lobe Epilepsy.

PubMed

Montes-Restrepo, Victoria; Carrette, Evelien; Strobbe, Gregor; Gadeyne, Stefanie; Vandenberghe, Stefaan; Boon, Paul; Vonck, Kristl; Mierlo, Pieter van

2016-07-01

We investigated the influence of different skull modeling approaches on EEG source imaging (ESI), using data of six patients with refractory temporal lobe epilepsy who later underwent successful epilepsy surgery. Four realistic head models with different skull compartments, based on finite difference methods, were constructed for each patient: (i) Three models had skulls with compact and spongy bone compartments as well as air-filled cavities, segmented from either computed tomography (CT), magnetic resonance imaging (MRI) or a CT-template and (ii) one model included a MRI-based skull with a single compact bone compartment. In all patients we performed ESI of single and averaged spikes marked in the clinical 27-channel EEG by the epileptologist. To analyze at which time point the dipole estimations were closer to the resected zone, ESI was performed at two time instants: the half-rising phase and peak of the spike. The estimated sources for each model were validated against the resected area, as indicated by the postoperative MRI. Our results showed that single spike analysis was highly influenced by the signal-to-noise ratio (SNR), yielding estimations with smaller distances to the resected volume at the peak of the spike. Although averaging reduced the SNR effects, it did not always result in dipole estimations lying closer to the resection. The proposed skull modeling approaches did not lead to significant differences in the localization of the irritative zone from clinical EEG data with low spatial sampling density. Furthermore, we showed that a simple skull model (MRI-based) resulted in similar accuracy in dipole estimation compared to more complex head models (based on CT- or CT-template). Therefore, all the considered head models can be used in the presurgical evaluation of patients with temporal lobe epilepsy to localize the irritative zone from low-density clinical EEG recordings.

[Analysis of clinical features and treatment outcomes of patients with tuberculous otitis media and mastoiditis].

PubMed

Hao, Xin-ping; Gong, Shu-sheng; Li, Yong-xin; Xia, Yin; Zhao, Shou-qin; Zheng, Jun; Zheng, Ya-li; Zhao, Yan-ling; Ma, Xiao-bo

2010-11-01

To analyze the clinical features and the surgical treatment outcomes of patients with tuberculous otitis media and mastoiditis. The medical records of 16 patients (18 ears) with tuberculous otitis media and mastoiditis, who received surgery in Beijing Tongren hospital, were reviewed. The common symptoms were otorrhea and hearing loss, and 3 patients demonstrated severe sensorineural hearing loss. Three patients demonstrated a peripheral-type facial palsy. Temporal bone high resolution CT scans demonstrated the entire tympanum and mastoid air cells were occupied by soft tissue. Eleven patients demonstrated bone destruction and sequestra was found in 7 temporal bones. Contemporary pulmonary tuberculosis were diagnosed in 7 of the 16 patients. Surgical removal of disease lesions in combination with anti-tuberculosis treatment were given to 15 patients. Other than 2 cases of tuberculous otitis media and mastoiditis diagnosed by pre-operational biopsy through the perforated tympanic membrane, the remaining 14 cases were diagnosed intra-operatively or post-operatively. No relapse of tuberculosis in the middle ear and mastoid were found after follow-up for more than 1 year, except for the one case that was lost to follow-up. The 3 cases of facial nerve palsy almost recovered to normal. Clinicians should suspect tuberculous otitis media and mastoiditis if clinical findings include refractory otorrhea, total occupation of the tympanic cavity and mastoid ari cells by soft tissue, and erosion of the bone or sequestra as shown by CT. A history of tuberculosis should be asked carefully in order to differentiate tuberculous otitis media and mastoiditis. The patients who received surgery and anti-tuberculosis chemotherapy achieved more rapid healing of the ear.

Music and epilepsy: a critical review.

PubMed

Maguire, Melissa Jane

2012-06-01

The effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl's gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native-born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Sub-hubs of baseline functional brain networks are related to early improvement following two-week pharmacological therapy for major depressive disorder.

PubMed

Shen, Yuedi; Yao, Jiashu; Jiang, Xueyan; Zhang, Lei; Xu, Luoyi; Feng, Rui; Cai, Liqiang; Liu, Jing; Wang, Jinhui; Chen, Wei

2015-08-01

Accumulating evidence suggests that early improvement after two-week antidepressant treatment is predictive of later outcomes of patients with major depressive disorder (MDD); however, whether this early improvement is associated with baseline neural architecture remains largely unknown. Utilizing resting-state functional MRI data and graph-based network approaches, this study calculated voxel-wise degree centrality maps for 24 MDD patients at baseline and linked them with changes in the Hamilton Rating Scale for Depression (HAMD) scores after two weeks of medication. Six clusters exhibited significant correlations of their baseline degree centrality with treatment-induced HAMD changes for the patients, which were mainly categorized into the posterior default-mode network (i.e., the left precuneus, supramarginal gyrus, middle temporal gyrus, and right angular gyrus) and frontal regions. Receiver operating characteristic curve and logistic regression analyses convergently revealed excellent performance of these regions in discriminating the early improvement status for the patients, especially the angular gyrus (sensitivity and specificity of 100%). Moreover, the angular gyrus was identified as the optimal regressor as determined by stepwise regression. Interestingly, these regions possessed higher centrality than others in the brain (P < 10(-3)) although they were not the most highly connected hubs. Finally, we demonstrate a high reproducibility of our findings across several factors (e.g., threshold choice, anatomical distance, and temporal cutting) in our analyses. Together, these preliminary exploratory analyses demonstrate the potential of neuroimaging-based network analysis in predicting the early therapeutic improvement of MDD patients and have important implications in guiding earlier personalized therapeutic regimens for possible treatment-refractory depression. © 2015 Wiley Periodicals, Inc.

Psychotherapeutic Treatment of a Gastrointestinal Disorder: Individual and Family Systems Perspectives.

ERIC Educational Resources Information Center

Bauknight, S. Terry

A 17-year-old boy presented for treatment with chronic diarrhea that had proven refractory to medical treatment for a period of five years. The problem was sufficiently debilitating to cause highly erratic school attendance. Anamnesis revealed no precipitating event, though it was discovered that the patient's mother was a moderately compensated,…

Surgical Intervention for Medically Refractory Hyperthyroidism.

PubMed

Knollman, Philip D; Giese, Ann; Bhayani, Mihir K

2016-05-01

Pediatric hyperthyroidism can be multifactorial, with Graves' disease (GD) being the most common etiology. Treatment focuses on identification of the cause of the hyperthyroidism and achieving a biochemical cure with symptom resolution. This article highlights the clinical presentation, diagnosis, and treatment of a pediatric patient with GD. [Pediatr Ann. 2016;45(5):e171-e175.]. Copyright 2016, SLACK Incorporated.

Oculoplastic technique of connecting a glaucoma valve shunt to extraorbital locations in cases of severe glaucoma.

PubMed

Rubin, Peter A D; Chang, Eli; Bernardino, Carlo Roberto; Hatton, Mark P; Dohlman, Claes H

2004-09-01

To describe a technique for inserting glaucoma shunts to the sinuses or the lacrimal sac as a means of lowering intraocular pressure in patients with refractory glaucoma associated with severe ocular surface disease. Nineteen patients with severe ocular surface disease necessitating a keratoprosthesis and with intractable glaucoma underwent placement of a modified Ahmed shunt to direct aqueous in the maxillary or ethmoid sinus or lacrimal sac. Intraocular pressure is presently well controlled without glaucoma medications in two thirds of patients. None of the patients had endophthalmitis. Established oculoplastic surgery techniques may be used to redirect aqueous to extraorbital locations and effectively lower intraocular pressure in patients with severe ocular surface disease and refractory glaucoma. This procedure has not been associated with endophthalmitis.

Nondiabetic ketoacidosis in a pregnant woman due to acute starvation with concomitant influenza A (H1N1) and respiratory failure.

PubMed

Skalley, G; Rodríguez-Villar, S

2018-02-28

Threatening refractory metabolic acidosis due to short-term starvation nondiabetic ketoacidosis is rarely reported. Severe ketoacidosis due to starvation itself is a rare occurrence, and more so in pregnancy with a concomitant stressful clinical situation. This case report presents a nondiabetic woman admitted in intensive care for respiratory failure type 1 during the third trimester of pregnancy with a severe metabolic acidosis refractory to medical treatment. We diagnosed the patient with acute starvation ketoacidosis based on her history and the absence of other causes of high anion gap metabolic acidosis after doing a rigorous analysis of her acid-base disorder. Crown Copyright © 2018. Publicado por Elsevier España, S.L.U. All rights reserved.

Deep brain stimulation of the anterior limb of the internal capsule for treatment of therapy-refractory obsessive compulsive disorder (OCD): a case study highlighting neurocognitive and psychiatric changes.

PubMed

Choudhury, Tabina K; Davidson, Joyce E; Viswanathan, Ashwin; Strutt, Adriana M

2017-04-01

Obsessive compulsive disorder (OCD) is an anxiety disorder characterized by repeated, unwanted thoughts and behaviors. Individuals with this condition often experience significant emotional distress secondary to their symptoms. Additionally, impairments in attention/concentration, processing speed, and executive functions are typically observed. The exact pathology of OCD remains unknown; consequently, it can be difficult to treat patients with severe symptomatology. Deep brain stimulation (DBS) may be a viable treatment option for individuals who do not respond to medication and/or cognitive behavioral therapy. The following case discusses DBS of the anterior limb of the internal capsule for a patient with severe, therapy-refractory OCD, including pre- to postoperative neurocognitive and psychiatric changes.

Management of Intracranial Hypertension

PubMed Central

Rangel-Castillo, Leonardo; Gopinath, Shankar; Robertson, Claudia S.

2008-01-01

Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate increased intracranial pressure. When intracranial pressure becomes elevated, it is important to rule out new mass lesions that should be surgically evacuated. Medical management of increased intracranial pressure should include sedation, drainage of cerebrospinal fluid, and osmotherapy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical management, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. Steroids are not indicated and may be harmful in the treatment of intracranial hypertension resulting from traumatic brain injury. PMID:18514825

[Burning mouth syndrome - a joint biopsychosocial approach].

PubMed

Arpone, Francesca; Combremont, Florian; Weber, Kerstin; Scolozzi, Paolo

2016-02-10

Burning mouth syndrome (BMS) is a medical condition that is often refractory to conventional diagnostic and therapeutic methods. Patients suffering from BMS can benefit from a biopsychosocial approach in a joint, medical-psychological consultation model. Such a consultation exists at Geneva University Hospitals, involving the collaboration of the maxillo-facial and oral surgery division and the division of liaison psychiatry and crisis intervention, in order to take into account the multiple factors involved in BMS onset and persistence. This article will describe BMS clinical presentation, and present an integrate approach to treat these patients.

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

Colectomy is a risk factor for venous thromboembolism in ulcerative colitis.

PubMed

Kaplan, Gilaad G; Lim, Allen; Seow, Cynthia H; Moran, Gordon W; Ghosh, Subrata; Leung, Yvette; Debruyn, Jennifer; Nguyen, Geoffrey C; Hubbard, James; Panaccione, Remo

2015-01-28

To compare venous thromboembolism (VTE) in hospitalized ulcerative colitis (UC) patients who respond to medical management to patients requiring colectomy. Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by: (1) responsive to inpatient medical therapy (n=382); (2) medically refractory requiring emergent colectomy (n=309); and (3) elective colectomy (n=329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course (i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications (i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios (OR) with 95%CI. The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparin prophylaxis. In contrast, VTE was higher among patients who underwent an emergent (8.7%) and elective (4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal (45.8%) followed by lower extremity (19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective (adjusted OR=3.69; 95%CI: 1.30-10.44) and emergent colectomy (adjusted OR=5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time (adjusted OR=1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE. VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.

[Classical medications in the treatment of inflammatory bowel diseases].

PubMed

Duvnjak, Marko; Bilić, Ante; Barsić, Neven; Tomasić, Vedran; Stojsavljević, Sanja

2013-04-01

The treatment of inflammatory bowel diseases is complex and requires individual approach to every single patient. Traditionally, the approach is based on introduction of so called "classical" medication into the treatment regimen, from ones less potent and with fewer side effects to the ones more toxic but also therapeutically more effective. Aminosalicylates were the first choice of treatment for a long time. However, the role of aminosalicylates is becoming more and more diminished, although they are still the drug of choice in the treatment of mild to moderate ulcerative colitis. Corticosteroids are the therapy of choice in treatment of active IBD for achieving remission in moderate to severe disease. Azathioprine and 6- mercaptopurine belong to a group of thiopurines with an immunomodulatory effect which, in Crohn's disease as well as in ulcerative colitis, primarily have a role in a steroid dependant or steroid refractory type of disease and in maintenance of remission. Lately, early introduction of these medications is proposed to enhance the number of patients that remain in remission. Methotrexate is used for the therapy of active and relapsing Crohn's disease and represents an alternative in patients who do not tolerate or do not respond to azathioprine or 6-mercaptopurine therapy. Cyclosporine is used in treating steroid refractory ulcerative colitis and in some patients can postpone the need for colectomy. Antibiotics do not have a proven effect on the course of inflammatory bowel diseases and their primary role is to treat septic complications. Classic medications today represent a standard in the management of inflammatory bowel diseases, and the combination of the previously mentioned drugs often has a more potent effect on the course of the disease than any medication on its own and their combination is still an object of investigations and clinical studies.

Clinical and neurobiological factors in the management of treatment refractory attention-deficit hyperactivity disorder.

PubMed

Shim, Se-Hoon; Yoon, Hee-Jung; Bak, Jeongjae; Hahn, Sang-Woo; Kim, Yong-Ku

2016-10-03

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often continues into adolescence and adulthood. Stimulants such as methylphenidate (MPH) and non-stimulants such as atomoxetine are effective medications for the treatment of ADHD. However, about 30% of patients do not respond to these medications. Pharmacological treatment for ADHD, although highly effective, is associated with marked variabilities in clinical response, optimal dosage needed and tolerability. This article provides an overview of up-to-date knowledge regarding the clinical and neurobiological factors which contribute to and help predict treatment-refractory ADHD. Pharmacogenetic, pharmacogenomics and neuroimaging studies are still controversial with respect to determining the associations between response to medication and genetic factors, thereby resulting in hypotheses that differences in the genetic factors and neuroimaging findings contribute to treatment outcome. Much research on the potential role of genotype in pharmacological effects has focused on the catecholaminergic gene related to executive functions. Many neuroimaging studies have also reported a relationship between treatment response and common patterns of brain structure or activity according to various genetic polymorphisms. When children, adolescents and adults with ADHD do not respond to MPH, we should consider additional pharmacological options, including other classes of psychostimulants, the nonstimulant atomoxetine, bupropion, tricyclic antidepressant, clonidine, guanfacine and lisdexamphetamine. Prudent choice of an appropriate medication and active engagement of children, parents, and teachers in daily management may help to ensure long-term adherence. Therefore, additional research might help to optimize the treatment of children, adolescents and adults with ADHD and to find new options for the treatment of patients who do not respond to stimulants and the other medications. Because these findings should be interpreted cautiously, further studies are needed to elucidate these issues more clearly. Copyright © 2016 Elsevier Inc. All rights reserved.

[Diode laser in "Malignant Glaucoma" treatment].

PubMed

Bresson Dumont, H; Ballereau, L; Lehoux, A; Santiago, P-Y

2006-05-01

Malignant glaucoma remains one of the most dramatic complications of ocular surgery. It can occur after glaucoma surgery but also after iridotomy, capsulotomy, or cataract extraction. However, the mechanisms remain unclear. to evaluate diode laser cyclodestruction as a complementary treatment in refractory malignant glaucoma. Seven women with malignant glaucoma with onset several months before (mean, 43 months; range, 12-96 months), in whom shallow anterior chamber and high IOP (25 mmHg +/- 5.5 treated with 2.86 +/- 0.9 topical and systemic medications) persisted despite prior surgical treatment (mean, 2; range, 1-5). Controlateral eyes had hyperopia (mean, +3.7 D, range, +1 to +6), five had shallow anterior chamber and high IOP. UBM detected plateau iris in four women. Seven eyes with malignant glaucoma and three controlateral eyes underwent cyclodestruction with diode laser (Viridis Twin Quantel Medical, laser, 810 nm), 22 burns around 270 degrees , 2 mm from the limbus for glaucomatous eyes and 15 inferior burns for controlateral eyes. Resolution of malignant glaucoma, with lower pressure (mean, 35%; range, 10%-70%), lower levels of medications (64%), final IOP at 13.2 mmHg (+/- 4.7), and deepening anterior chamber was achieved in all cases (mean follow-up, 18 months; range, 12-22). Cycloplegic topical treatment was stopped in 70% of cases. Diode laser cyclodestruction can help to resolve refractory malignant glaucoma. Larger UBM studies could help us to better understand the mechanisms of malignant glaucoma.

Peripheral nerve field stimulation in chronic abdominal pain.

PubMed

Paicius, Richard M; Bernstein, Clifford A; Lempert-Cohen, Cheryl

2006-07-01

Spinal Cord Stimulation (SCS) has become an accepted therapeutic modality for the treatment of intractable pain syndromes, primarily used today in the settings of failed back surgery syndrome, neuropathic back and limb pain. The use of spinal cord stimulators for peripheral nerve field electrostimulation is becoming increasingly recognized as a safe, effective alternative for chronic pain conditions that are refractory to medical management and do not respond to traditional dorsal column stimulation. Advances in technology have allowed for minimally invasive percutaneous placement of multipolar leads with complex programmable systems to provide patient- controlled relief of pain in precisely targeted regions. With these improvements in hardware, the use of Peripheral Nerve Field Stimulation (PNFS) appears to have an untapped potential for providing patients with pain relief for a wider range of underlying conditions than was previously believed possible. We present three cases, each with a different etiology of chronic abdominal pain: one with inguinal neuralgia, one with chronic pancreatitis, and one with pain following liver transplant. Each patient was refractory to conventional medical approaches. For all three patients, PNFS provided significant relief from pain, enabling patients to decrease or discontinue their opioid medications and to enjoy significant improvement in their quality of life. We conclude that PNFS is a safe, effective and minimally invasive treatment that may be used successfully for a wide variety of indications including chronic abdominal pain.

Effect of intradiscal pulsed radiofrequency on refractory chronic discogenic neck pain: A case report.

PubMed

Kwak, So Young; Chang, Min Cheol

2018-04-01

Despite medication, exercise, and medical intervention, many patients complain of persistent discogenic neck pain. To manage discogenic neck pain, we performed intradiscal pulsed radiofrequency (PRF) stimulation in a patient with chronic discogenic neck pain refractory to oral medication and epidural steroid injection. A 26-year-old man presented with a numeric rating scale (NRS) score of 7 for chronic neck pain. His pain was worse when the neck was held in one position for a prolonged period. There was no pain in the upper extremities. Discography was positive at C4-5. Based on the pain characteristics, and the result of discography, we diagnosed him as having discogenic neck pain originating from C4-5. Intradiscal PRF on the C4-5 intervertebral disc was performed under C-arm fluoroscopy. The PRF treatment was administered at 2 Hz and a 20-ms pulsed width for 20 minutes at 60 V with the constraint that the electrode tip temperature should not exceed 42°C. At the 2-week, and 1-month follow-up visits, the patient's pain was completely relieved. At 2, and 3 months after intradiscal PRF, the pain was scored as NRS 2. No adverse effects of intradiscal PRF stimulation were observed. Application of intradiscal PRF appears to be an effective and safe technique for treating chronic discogenic neck pain.

Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy.

PubMed

Kim, Jon Soo; Kim, Hunmin; Lim, Byung Chan; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Hwang, Hee

2014-06-01

To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients' epilepsy and the outcome of lacosamide treatment was gathered and analyzed. Twenty-one patients (16 boys, 5 girls) were included, with a median age of 13.9 (range, 1.2-17.9) years. The mean number of concomitant antiepileptic drugs was 3.0 (range, 1-6) and the mean duration of follow-up was 10.1 (range, 6.1-13.0) months. The mean maintenance dose of lacosamide was 5.4 (range, 1.4-9.8) mg/kg/day. Fourteen patients (67%) were responders; four of these were seizure free at the last follow-up. Seven patients (33%) were nonresponders: two of these presented with <50% seizure reduction and five showed no change in seizure frequency. Two patients (10%) discontinued oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-related adverse events were observed in eight of the 21 patients (38%). Lacosamide represents a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and is well tolerated. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Paroxysmal events during prolonged video-video electroencephalography monitoring in refractory epilepsy.

PubMed

Sanabria-Castro, A; Henríquez-Varela, F; Monge-Bonilla, C; Lara-Maier, S; Sittenfeld-Appel, M

2017-03-16

Given that epileptic seizures and non-epileptic paroxysmal events have similar clinical manifestations, using specific diagnostic methods is crucial, especially in patients with drug-resistant epilepsy. Prolonged video electroencephalography monitoring during epileptic seizures reveals epileptiform discharges and has become an essential procedure for epilepsy diagnosis. The main purpose of this study is to characterise paroxysmal events and compare patterns in patients with refractory epilepsy. We conducted a retrospective analysis of medical records from 91 patients diagnosed with refractory epilepsy who underwent prolonged video electroencephalography monitoring during hospitalisation. During prolonged video electroencephalography monitoring, 76.9% of the patients (n=70) had paroxysmal events. The mean number of events was 3.4±2.7; the duration of these events was highly variable. Most patients (80%) experienced seizures during wakefulness. The most common events were focal seizures with altered levels of consciousness, progressive bilateral generalized seizures and psychogenic non-epileptic seizures. Regarding all paroxysmal events, no differences were observed in the number or type of events by sex, in duration by sex or age at onset, or in the number of events by type of event. Psychogenic nonepileptic seizures were predominantly registered during wakefulness, lasted longer, started at older ages, and were more frequent in women. Paroxysmal events recorded during prolonged video electroencephalography monitoring in patients with refractory epilepsy show similar patterns and characteristics to those reported in other latitudes. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

Spectrum of the WHO Classification De Novo Myelodysplastic Syndrome: Experience from Southern Pakistan.

PubMed

Sultan, Sadia; Irfan, Syed Mohammed; Jawed, Syeda Narisa

2016-01-01

Myelodysplastic syndrome (MDS) is a clonal disorder of hemopoeitic stem cells, characterized by infective hematopoiesis, peripheral cytopenias along with hypercellularity of marrow and marked dysplastic features. Our aim was to study the spectrum of the WHO classification in adult Pakistani patients with MDS at disease presentation. This retrospective descriptive study was conducted at Liaquat National Hospital and Medical College, extending from January 2010 to December 2014. Patient data were retrieved from the maintained archives. Overall, 45 patients were diagnosed at our institution with de novo MDS during the study period. There were 28 males and 17 females. Age ranged between 18 and 95 years with a mean of 57.6±17.4 years. The male to female ratio was 1.7:1. According to the WHO classification, 53.3% had refractory cytopenia with multilineage dysplasia, 22.2% had refractory cytopenia with unilineage dysplasia, 4.4% each had refractory anemia with excess of blasts-1 and II and 15.5% had MDS unclassified. The main presenting complaints were generalized fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and weight loss (11.1%). Physical examination revealed pallor in 37.7%, followed by petechial and purpuric rashes in 20% of patients. Hemoglobin was <10 g/dl in 41 (91.1%). Pancytopenia and bicytopenia were noted in 18 (40%) and 14 (31.1%) respectively. MDS in our patients presents at a relatively young age. Refractory c ytopenia with multilineage dysplasia was the dominant disease variant in our setting.

High-intensity focused ultrasound treatment in refractory glaucoma patients: results at 1 year of prospective clinical study.

PubMed

Melamed, Shlomo; Goldenfeld, Modi; Cotlear, Daniel; Skaat, Alon; Moroz, Iris

2015-01-01

To evaluate the safety and efficacy of the ultrasonic circular cyclo-coagulation procedure using high-intensity focused ultrasound by a miniaturized annular device containing 6 piezoceramic transducers in patients with refractory glaucoma. This was a prospective interventional noncomparative study of 20 eyes of 20 patients with refractory glaucoma. All eyes were treated with 6 activated transducers operating at 21 MHz. Ultrasound biomicroscopy and a complete ophthalmic examination were performed before the procedure and at 1 day, 1 week, and 1, 3, 6, and 12 months after the procedure. Primary outcomes were surgical success (defined as intraocular pressure (IOP) reduction from baseline ≥20% and IOP >5 mm Hg) at the last follow-up visit. Secondary outcomes were mean IOP at each follow-up visit compared to baseline, medication use, complications, and re-interventions. Intraocular pressure was significantly reduced (p<0.01) from a mean preoperative value of 36.4 ± 5.7 mm Hg to a mean postoperative value of 22.5 ± 10.3 mm Hg at 12 months. Four patients needed to be re-treated. The mean IOP reduction achieved was 38%. Surgical success was achieved in 13 of 20 eyes (65%). No major intraoperative or postoperative complications occurred. Ultrasonic circular cyclo-coagulation using high-intensity focused ultrasound delivered by a circular miniaturized device containing 6 piezoceramic transducers is an effective and well-tolerated method to reduce IOP in patients with refractory glaucoma.

Does education play a role in language reorganization after surgery in drug refractory temporal lobe epilepsy: An fMRI based study?

PubMed

Chaudhary, Kapil; Ramanujam, Bhargavi; Kumaran, S Senthil; Chandra, P Sarat; Wadhawan, Ashima Nehra; Garg, Ajay; Tripathi, Manjari

2017-10-01

Patients with drug refractory epilepsy (DRE) and a high level of education may differ in their language recovery after surgery. Our aim was to determine whether there were differences in the extent of improvement and pattern of reorganization of language functions on functional magnetic resonance imaging (fMRI) after surgery to treat refractory temporal lobe epilepsy (TLE) between patients with more than 12 years of formal education versus those with a shorter period of regular schooling. After approval by an institutional ethics committee, 60 right-handed, adult patients of left TLE and 20 right-handed, healthy controls were recruited to the study. Multiple aspects of language (Repetition, Naming, Word fluency, Visual word and Comprehension reading) were tested using the Indian Aphasia Battery (IAB) in the Hindi language; fMRI was performed using a standardized Hindi language paradigm (lexical, semantic, syntactic and comprehension components) in both cases and controls, before and after an anterior temporal lobectomy (in cases) with a 1.5T MR Scanner. An array of performance tests of intelligence and the verbal adult intelligence scale (VAIS) were used to measure the Intelligence Quotient (IQ) in Left TLE (LTLE) patients before and after surgery. Language laterality was estimated using the laterality index (LI-toolbox-spm8). Cohen's d test was performed to determine the effect sizes of the differences in the IAB scores, and Pearson's correlation was applied between regional (IFG and STG) activation in controls and TLE patients with more than 12 years of schooling [higher educational status (HES subgroup)] and those with less than 12 years of schooling [lower educational status (LES subgroup)]. At the baseline, clinical testing with IAB showed better scores in controls than in cases. Better scores were observed in subjects with higher levels of education than in those with lower levels of education. An improvement was observed in IQ scores in both the HES and LES groups after ATLR; significant worsening in the abstract ability subtest was noted in the LES group, whereas in the HES group there was an improvement. Blood-oxygen-level dependent (BOLD) activation during language tasks was observed in both cerebral hemispheres in the TLE cases, while it was observed in the traditional left hemispheric language areas in controls. Postoperatively, greater BOLD activation was observed in the left inferior frontal gyri (IFG, r=0.65 * ; p<0.05), middle frontal gyrus (MFG, r=0.77 ** ; p<0.01) superior temporal gyri (STG, r=0.88 * p<0.02) and angular gyrus (AG, r=0.73 * ; p<0.04) in HES compared to LES subjects. Similarly, LI showed left lateralization of the frontal (LIw=0.77 & 0.71) and temporal (LIw=0.74 & 0.5) regions in controls and the TLE group (post-surgery) compared to the pre-surgery group during language tasks. Greater improvement in language skills and BOLD activation in the left hemisphere in TLE-patients (after epilepsy surgery) with a high level of education was similar to that of healthy controls, implying that education has an effect on the functional reorganization/recovery of language areas. Copyright © 2017 Elsevier B.V. All rights reserved.

The Evaluation of a Temporal Reasoning System in Processing Clinical Discharge Summaries

PubMed Central

Zhou, Li; Parsons, Simon; Hripcsak, George

2008-01-01

Context TimeText is a temporal reasoning system designed to represent, extract, and reason about temporal information in clinical text. Objective To measure the accuracy of the TimeText for processing clinical discharge summaries. Design Six physicians with biomedical informatics training served as domain experts. Twenty discharge summaries were randomly selected for the evaluation. For each of the first 14 reports, 5 to 8 clinically important medical events were chosen. The temporal reasoning system generated temporal relations about the endpoints (start or finish) of pairs of medical events. Two experts (subjects) manually generated temporal relations for these medical events. The system and expert-generated results were assessed by four other experts (raters). All of the twenty discharge summaries were used to assess the system’s accuracy in answering time-oriented clinical questions. For each report, five to ten clinically plausible temporal questions about events were generated. Two experts generated answers to the questions to serve as the gold standard. We wrote queries to retrieve answers from system’s output. Measurements Correctness of generated temporal relations, recall of clinically important relations, and accuracy in answering temporal questions. Results The raters determined that 97% of subjects’ 295 generated temporal relations were correct and that 96.5% of the system’s 995 generated temporal relations were correct. The system captured 79% of 307 temporal relations determined to be clinically important by the subjects and raters. The system answered 84% of the temporal questions correctly. Conclusion The system encoded the majority of information identified by experts, and was able to answer simple temporal questions. PMID:17947618

Assessment of skills using a virtual reality temporal bone surgery simulator.

PubMed

Linke, R; Leichtle, A; Sheikh, F; Schmidt, C; Frenzel, H; Graefe, H; Wollenberg, B; Meyer, J E

2013-08-01

Surgery on the temporal bone is technically challenging due to its complex anatomy. Precise anatomical dissection of the human temporal bone is essential and is fundamental for middle ear surgery. We assessed the possible application of a virtual reality temporal bone surgery simulator to the education of ear surgeons. Seventeen ENT physicians with different levels of surgical training and 20 medical students performed an antrotomy with a computer-based virtual temporal bone surgery simulator. The ease, accuracy and timing of the simulated temporal bone surgery were assessed using the automatic assessment software provided by the simulator device and additionally with a modified Final Product Analysis Scale. Trained ENT surgeons, physicians without temporal bone surgical training and medical students were all able to perform the antrotomy. However, the highly trained ENT surgeons were able to complete the surgery in approximately half the time, with better handling and accuracy as assessed by the significant reduction in injury to important middle ear structures. Trained ENT surgeons achieved significantly higher scores using both dissection analysis methods. Surprisingly, there were no significant differences in the results between medical students and physicians without experience in ear surgery. The virtual temporal bone training system can stratify users of known levels of experience. This system can be used not only to improve the surgical skills of trained ENT surgeons for more successful and injury-free surgeries, but also to train inexperienced physicians/medical students in developing their surgical skills for the ear.

Evidence for a basal temporal visual language center: cortical stimulation producing pure alexia.

PubMed

Mani, J; Diehl, B; Piao, Z; Schuele, S S; Lapresto, E; Liu, P; Nair, D R; Dinner, D S; Lüders, H O

2008-11-11

Dejerine and Benson and Geschwind postulated disconnection of the dominant angular gyrus from both visual association cortices as the basis for pure alexia, emphasizing disruption of white matter tracts in the dominant temporooccipital region. Recently functional imaging studies provide evidence for direct participation of basal temporal and occipital cortices in the cognitive process of reading. The exact location and function of these areas remain a matter of debate. To confirm the participation of the basal temporal region in reading. Extraoperative electrical stimulation of the dominant hemisphere was performed in three subjects using subdural electrodes, as part of presurgical evaluation for refractory epilepsy. Pure alexia was reproduced during cortical stimulation of the dominant posterior fusiform and inferior temporal gyri in all three patients. Stimulation resulted in selective reading difficulty with intact auditory comprehension and writing. Reading difficulty involved sentences and words with intact letter by letter reading. Picture naming difficulties were also noted at some electrodes. This region is located posterior to and contiguous with the basal temporal language area (BTLA) where stimulation resulted in global language dysfunction in visual and auditory realms. The location corresponded with the visual word form area described on functional MRI. These observations support the existence of a visual language area in the dominant fusiform and occipitotemporal gyri, contiguous with basal temporal language area. A portion of visual language area was exclusively involved in lexical processing while the other part of this region processed both lexical and nonlexical symbols.

Expression of SHANK3 in the Temporal Neocortex of Patients with Intractable Temporal Epilepsy and Epilepsy Rat Models.

PubMed

Zhang, Yanke; Gao, Baobing; Xiong, Yan; Zheng, Fangshuo; Xu, Xin; Yang, Yong; Hu, Yida; Wang, Xuefeng

2017-07-01

SH3 and multiple ankyrin (ANK) repeat domain 3 (SHANK3) is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. SHANK3 plays an important role in the formation and maturation of excitatory synapses. In the brain, SHANK3 directly or indirectly interacts with various synaptic molecules including N-methyl-D-aspartate receptor, the metabotropic glutamate receptor (mGluR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Previous studies have shown that Autism spectrum disorder is a result of mutations of the main SHANK3 isoforms, which may be due to deficit in excitatory synaptic transmission and plasticity. Recently, accumulating evidence has demonstrated that overexpression of SHANK3 could induce seizures in vivo. However, little is known about the role of SHANK3 in refractory temporal lobe epilepsy (TLE). Therefore, we investigated the expression pattern of SHANK3 in patients with intractable temporal lobe epilepsy and in pilocarpine-induced models of epilepsy. Immunofluorescence, immunohistochemistry, and western blot analysis were used to locate and determine the expression of SHANK3 in the temporal neocortex of patients with epilepsy, and in the hippocampus and temporal lobe cortex of rats in a pilocarpine-induced epilepsy model. Double-labeled immunofluorescence showed that SHANK3 was mainly expressed in neurons. Western blot analysis confirmed that SHANK3 expression was increased in the neocortex of TLE patients and rats. These results indicate that SHANK3 participates in the pathology of epilepsy.

Efficacy of Enhanced External Counterpulsation in Patients With Chronic Refractory Angina on Canadian Cardiovascular Society (CCS) Angina Class: An Updated Meta-Analysis.

PubMed

Zhang, Chunmei; Liu, Xiangjuan; Wang, Xiaomeng; Wang, Qi; Zhang, Yun; Ge, Zhiming

2015-11-01

A growing number of patients with chronic artery disease suffer from angina, despite the optimal medical management (ie, β-blockers, calcium channel blockers, and long-acting nitrates) and revascularization. Currently, enhanced external counterpulsation (EECP) therapy has been verified as a noninvasive, safe therapy for refractory angina. The study was designed to evaluate the efficacy of EECP in patients with chronic refractory angina according to Canadian Cardiovascular Society (CCS) angina class.We identified systematic literature through MEDLINE, EMBASE, the Cochrane Clinical Trials Register Database, and the ClinicalTrials. gov Website from 1990 to 2015. Studies were considered eligible if they were prospective and reported data on CCS class before and after EECP treatment. Meta-analysis was performed to assess the efficacy of EECP therapy by at least 1 CCS angina class improvement, and proportion along with the 95% confidence interval (CI) was calculated. Statistical heterogeneity was calculated by I statistic and the Q statistic. Sensitivity analysis was addressed to test the influence of trials on the overall pooled results. Subgroup analysis was applied to explore potential reasons for heterogeneity.Eighteen studies were enrolled in our meta-analysis. Pooled analysis showed 85% of patients underwent EECP had a reduction by at least one CCS class (95%CI 0.81-0.88, I = 58.5%, P < 0.001). The proportion of patients enrolled at primarily different studies with chronic heart failure (CHF) improved by at least 1 CCS class was about 84% after EECP (95%CI 0.81-0.88, I = 32.7%, P = 0.1668). After 3 large studies were excluded, the pooled proportion was 82% (95%CI 0.79-0.86, I = 18%, P = 0.2528). Funnel plot indicated that some asymmetry while the Begg and Egger bias statistic showed no publication bias (P = 0.1495 and 0.2859, respectively).Our study confirmed that EECP provided an effective treatment for patients who were unresponsive to medical management and/or invasive therapy. However, the long-term benefits of EECP therapy needed further studies to evaluate in the management of chronic refractory angina.

Tumor necrosis factor alpha blocking agents as treatment for ulcerative colitis intolerant or refractory to conventional medical therapy: a meta-analysis.

PubMed

Lv, Ruxi; Qiao, Weiguang; Wu, Zhiyong; Wang, Yinjun; Dai, Shixue; Liu, Qiang; Zheng, Xuebao

2014-01-01

Efficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results. To assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy. Pubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects. Eight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23). TNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.

Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation.

PubMed

Li, Congxin; Cesbron, François; Oehler, Michael; Brunner, Michael; Höfer, Thomas

2018-04-25

Gene regulation is a complex non-equilibrium process. Here, we show that quantitating the temporal regulation of key gene states (transcriptionally inactive, active, and refractory) provides a parsimonious framework for analyzing gene regulation. Our theory makes two non-intuitive predictions. First, for transcription factors (TFs) that regulate transcription burst frequency, as opposed to amplitude or duration, weak TF binding is sufficient to elicit strong transcriptional responses. Second, refractoriness of a gene after a transcription burst enables rapid responses to stimuli. We validate both predictions experimentally by exploiting the natural, optogenetic-like responsiveness of the Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we demonstrate that differential regulation of WCC target genes is caused by different gene activation rates, not different TF occupancy, and that these rates are tuned by both the core promoter and the distance between TF-binding site and core promoter. In total, our work demonstrates the relevance of a kinetic, non-equilibrium framework for understanding transcriptional regulation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

PubMed Central

LINKE, R.; LEICHTLE, A.; SHEIKH, F.; SCHMIDT, C.; FRENZEL, H.; GRAEFE, H.; WOLLENBERG, B.; MEYER, J.E.

2013-01-01

SUMMARY Surgery on the temporal bone is technically challenging due to its complex anatomy. Precise anatomical dissection of the human temporal bone is essential and is fundamental for middle ear surgery. We assessed the possible application of a virtual reality temporal bone surgery simulator to the education of ear surgeons. Seventeen ENT physicians with different levels of surgical training and 20 medical students performed an antrotomy with a computer-based virtual temporal bone surgery simulator. The ease, accuracy and timing of the simulated temporal bone surgery were assessed using the automatic assessment software provided by the simulator device and additionally with a modified Final Product Analysis Scale. Trained ENT surgeons, physicians without temporal bone surgical training and medical students were all able to perform the antrotomy. However, the highly trained ENT surgeons were able to complete the surgery in approximately half the time, with better handling and accuracy as assessed by the significant reduction in injury to important middle ear structures. Trained ENT surgeons achieved significantly higher scores using both dissection analysis methods. Surprisingly, there were no significant differences in the results between medical students and physicians without experience in ear surgery. The virtual temporal bone training system can stratify users of known levels of experience. This system can be used not only to improve the surgical skills of trained ENT surgeons for more successful and injury-free surgeries, but also to train inexperienced physicians/medical students in developing their surgical skills for the ear. PMID:24043916

[Autism spectrum disorder and epilepsy: the role of ketogenic diet].

PubMed

Garcia-Penas, J J

2016-01-01

Between 5-40% of autistic patients will develop epilepsy. Most individuals with autism and epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. For this population, alternative treatments such as ketogenic diet (KD) can be highly efficacious and should be seriously considered. To discuss the use of the KD in refractory pediatric epilepsy and its role in patients with autism and epilepsy. KD is an effective and well-tolerated treatment for refractory childhood epilepsy, including those patients who associate autism and epilepsy. Accurate characterization of the electroclinical epilepsy syndrome is the key to deciding when to consider the KD. Otherwise, the positive effect of KD for treating mitochondrial oxidative disorders and different models of autistic animals suggest that KD could be a good alternative treatment for autistic patients. Based on the demonstrated efficacy of KD in patients who associate both epilepsy and autism, KD treatment has been recently used in the treatment of autism spectrum disorders; however, there is lacking of controlled studies to define the real efficacy of this therapy. A well designed randomized controlled study is needed to determine whether KD is really efficacious for these patients.

Excimer laser therapy and narrowband ultraviolet B therapy for exfoliative cheilitis.

PubMed

Bhatia, Bhavnit K; Bahr, Brooks A; Murase, Jenny E

2015-06-01

Exfoliative cheilitis is a condition of unknown etiology characterized by hyperkeratosis and scaling of vermilion epithelium with cyclic desquamation. It remains largely refractory to treatment, including corticosteroid therapy, antibiotics, antifungals, and immunosuppressants. We sought to evaluate the safety and efficacy of excimer laser therapy and narrowband ultraviolet B therapy in female patients with refractory exfoliative cheilitis. We reviewed the medical records of two female patients who had been treated unsuccessfully for exfoliative cheilitis. We implemented excimer laser therapy, followed by hand-held narrowband UVB treatments for maintenance therapy, and followed them for clinical improvement and adverse effects. Both patients experienced significant clinical improvement with minimal adverse effects with excimer laser therapy 600-700 mJ/cm 2 twice weekly for several months. The most common adverse effects were bleeding and burning, which occurred at higher doses. The hand-held narrowband UVB unit was also an effective maintenance tool. Limitations include small sample size and lack of standardization of starting dose and dose increments. Excimer laser therapy is a well-tolerated and effective treatment for refractory exfoliative cheilitis with twice weekly laser treatments of up to 700 mJ/cm 2 . Transitioning to the hand-held narrowband UVB device was also an effective maintenance strategy.

[End-of-life in specialized medical pediatrics department: A French national survey].

PubMed

Ravanello, Alice; Desguerre, Isabelle; Frache, Sandra; Hubert, Philippe; Orbach, Daniel; Aubry, Régis

2017-03-01

In France, most of children die in the hospital. This national survey aimed to achieve better understanding of end-of life care in specialized medical pediatrics departments for children facing the end-of-life, identify the available resources, put forward the difficulties encountered by professionals and describe end-of-life paths of children who died in these departments. This study is based on a nationwide survey conducted among all existing specialized medical pediatrics departments (onco-haematology, neurology, reanimation) in France in 2015. Among 94 specialized medical pediatrics departments in France, 53 participated in our survey (response rate=56%). At the time of the survey, 13% of inpatients were facing the end-of-life. Regarding training, 13% of departments did not have personnel trained in palliative care and 21% did not set up any professional support. However, when taking care of a child's end of life in 2014, 77% of these departments solicited a regional resource team of pediatric palliative care. This survey helps describe 225 end-of-life paths of children decease of a terminal illness in the specialized pediatrics departments. Seventy-two percent suffered from refractory symptoms before their death, 64% were concerned by a terminal sedation and 75% by a limitation of life-sustaining treatment decision. End-of-life care is a reality for specialized pediatrics departments. The frequency of major and refractory symptoms often requires the completion of sedation. The resources of service are acceptable but some deficiencies have been noted especially concerning training and support for caregivers, adaptation of premises or family support. Copyright © 2017. Published by Elsevier SAS.

A Physician's Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT).

PubMed

Brown, Tanida; Shao, Wanda; Ayub, Shehzad; Chong, David; Cornelius, Christian

2017-01-01

N,N-dimethyltryptamine (DMT) is a psychoactive substance that has been gaining popularity in therapeutic and recreational use. This is a case of a physician who chronically took DMT augmented with phenelzine in an attempt to self-medicate refractory bipolar depression. His presentation of altered mental status, mania, and psychosis is examined in regards to his DMT use. This case discusses DMT, the possible uses of DMT, and the theorized mechanism of DMT in psychosis and treatment of depression, particularly involving its agonist activity at 5-HT1A, 5-HT2A, and 5-HT2C. It is also important to recognize the dangers of self-medication, particularly amongst physicians.

Clinical Investigation.

DTIC Science & Technology

1979-09-30

Aeling, J.L. and Chalet, M.D.: Collagen : Basic Science and Re:ated Diseases. Accepted for Publication. J. of Assoc. of Military Derm., 1979...102 Minoxidil as an Antihypertensive in Patients Refractory to Available Medications (T) (P) (PR). ...... . 037 75/107 A Comparison of the Results of...of Systemic Scleroderma with Minoxidil (U-1858) (0) .... ........................... 100 78/115 The Effect of Immunotherapy on the Tissue Threshold

Studies of the Biology of Phleboviruses in Sandflies.

DTIC Science & Technology

1983-02-01

8217Ahiebotomus fever, sand fly fever, arbovirus, medical entomology, Phiebotomus, Lutzomyia, vector-borne diseases, insect cell cultures, _)_Laboratory...parenteral administration. Most of the viruses replicated in sand flies after intrathorazic inoculation; however, the insects were quite refractory to oral...cells was also established and tested for its ability to support the growth of a number of different arbaviruses. Most of the rhabdoviruses

A Review of Palliative Sedation.

PubMed

Bobb, Barton

2016-09-01

Palliative sedation has become a standard practice to treat refractory symptoms at end-of-life. Dyspnea and delirium are the two most commonly treated symptoms. The medications used in palliative sedation are usually benzodiazepines, barbiturates, antipsychotics, and/or anesthetics. Some ethical considerations remain, especially surrounding the use of palliative sedation in psychological distress and existential suffering. Copyright © 2016 Elsevier Inc. All rights reserved.

Greater occipital nerve neuralgia caused by pathological arterial contact: treatment by surgical decompression.

PubMed

Cornely, Christiane; Fischer, Marius; Ingianni, Giulio; Isenmann, Stefan

2011-04-01

Occipital nerve neuralgia is a rare cause of severe headache, and may be difficult to treat. We report the case of a patient with occipital nerve neuralgia caused by pathological contact of the nerve with the occipital artery. The pain was refractory to medical treatment. Surgical decompression yielded complete remission. © 2010 American Headache Society.

Accurate 3D Modeling of Breast Deformation for Temporal Mammogram Registration

DTIC Science & Technology

2009-09-01

U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION...MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland...Towards Registration of Temporal Mammograms by Finite Element Simulation of MR Breast Volumes”, Proceedings of SPIE Medical Imaging 2008 2. Qiu Y

Optimal management of collagenous colitis: a review

PubMed Central

O’Toole, Aoibhlinn

2016-01-01

Collagenous colitis (CC) is an increasingly recognized cause of chronic inflammatory bowel disease characterized by watery non-bloody diarrhea. As a lesser studied inflammatory bowel disease, many aspects of the CC’s natural history are poorly understood. This review discusses strategies to optimally manage CC. The goal of therapy is to induce clinical remission, <3 stools a day or <1 watery stool a day with subsequent improved quality of life (QOL). Antidiarrheal can be used as monotherapy or with other medications to control diarrhea. Budesonide therapy has revolutionized treatment and is superior to prednisone, however, the treatment is associated with high-relapse rates and the management of refractory disease is challenging. Ongoing trials will address the safety and efficacy of low-dose maintenance therapy. For those with refractory disease, case reports and case series support the role of biologic agents. Diversion of the fecal stream normalizes colonic mucosal changes and ileostomy may be considered where anti-tumor necrosis factor (TNF)-α agents are contraindicated. Underlying celiac disease, bile salt diarrhea, and associated thyroid dysfunction should be ruled out. The author recommends smoking cessation as well as avoidance of nonsteroidal anti-inflammatories as well as other associated medications. PMID:26929656

Treatment of Established Status Epilepticus.

PubMed

Falco-Walter, Jessica J; Bleck, Thomas

2016-04-25

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

PubMed

Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

2016-05-01

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic idiopathic intestinal pseudo-obstruction treated by near total small bowel resection: a 20-year experience.

PubMed

Lapointe, Roch

2010-12-01

Patients suffering from chronic idiopathic intestinal pseudo-obstruction (CIIPO) clearly benefit from home parenteral nutrition (HPN) to maintain adequate nutritional status and general health. But intestinal dismotility can seriously disturb their quality of life (QOL) to the point of making it intolerable. Report our clinical experience on the management of chronic severe occlusive symptoms in CIIPO by near total small bowel resection. A 20-year retrospective study of eight patients with end-stage CIIPO maintained on HPN and suffering of chronic occlusive symptoms refractory to medical treatment underwent extensive small bowel resection preserving less than 70 cm of total small bowel and less than 20 cm of ileum. The jejunum was anastomosed either to the ileum or to the colon. Six patients were completely relieved from obstructive symptoms. Two patients needed a second operation to remove the residual ileum because of recurrent symptoms. Two were significantly improved. There was no post-operative death. All patients experienced a significant improvement in their QOL. Near total small bowel resection appears to be a safe and effective procedure in end-stage CIIPO patients, refractory to optimal medical treatment.

Treatment of Established Status Epilepticus

PubMed Central

Falco-Walter, Jessica J.; Bleck, Thomas

2016-01-01

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

Treatment of Chronic Cough.

PubMed

Soni, Resha S; Ebersole, Barbara; Jamal, Nausheen

2017-01-01

Objective Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen. Study Design A case series with planned chart review of patients treated for chronic cough. Setting The review was performed with an outpatient electronic health record system at a tertiary care center. Subjects and Methods The charts of all patients treated for chronic cough by a single laryngologist over a 30-month period were analyzed. Patients' response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy. Results Thirty-eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech-language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms. Conclusion Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.

Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy.

PubMed

Ngo, Ly; Sperling, Michael R; Skidmore, Christopher; Mintzer, Scott; Nei, Maromi

2017-04-01

Frequent interictal epileptiform abnormalities may correlate with poor prognosis after temporal lobe resection for refractory epilepsy. To date, studies have focused on limited resections such as selective amygdalohippocampectomy and apical temporal lobectomy without hippocampectomy. However, it is unclear whether the frequency of spikes predicts outcome after standard anterior temporal lobectomy. Preoperative scalp video-EEG monitoring data from patients who subsequently underwent anterior temporal lobectomy over a three year period and were followed for at least one year were reviewed for the frequency of interictal epileptiform abnormalities. Surgical outcome for those patients with frequent spikes (>60/h) was compared with those with less frequent spikes. Additionally, spike frequency was evaluated as a continuous variable and correlated with outcome to determine if increased spike frequency correlated with worse outcome, as assessed by modified Engel Class outcome. Forty-seven patients (18 men, 29 women; mean age 40 years at surgery) were included. Forty-six patients had standard anterior temporal lobectomy (24 right, 22 left) and one had a modified left temporal lobectomy. There was no significant difference in seizure outcome between those with frequent (57% Class I) vs. those with less frequent (58% Class I) spikes. Increased spike frequency did not correlate with worse outcome. Greater than 20 complex partial seizures/month and generalized tonic-clonic seizures within one year of surgery correlated with worse outcome. This study suggests that absolute spike frequency does not predict seizure outcome after anterior temporal lobectomy unlike in selective procedures, and should not be used as a prognostic factor in this population. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Long-term clinical outcomes of Ahmed valve implantation in patients with refractory glaucoma

PubMed Central

Lee, Chang Kyu; Ma, Kyoung Tak; Hong, Young Jae

2017-01-01

Purpose To evaluate the long-term efficacy of intraocular pressure (IOP) reduction and complications of Ahmed Glaucoma Valve (AGV) implantation in patients with refractory glaucoma. Design Retrospective study. Subjects The study involved 302 refractory glaucoma patients who underwent AGV implantation and had a minimum follow-up of 6 months between March 1995 and December 2013. Methods An operation was defined as successful when (1) the postoperative IOP remained between 5 and 21 mmHg and was reduced 30% compared to the baseline IOP with or without medication, (2) there was no loss of light perception or vision-threatening severe complications, and (3) no additional filtering or aqueous drainage surgery was required. Clinical records were reviewed. Main outcome measures IOP, anti-glaucoma medications, and complications Results The mean follow-up period was 62.25 months (range, 6 to 190 months). The cumulative probability of success was 89% at 6 months, 81% at 1 year, 66% at 3 years, 44% at 10 years, and 26% at 15 years. IOP was reduced from a mean of 32.2 ± 10.5 mmHg to 18.6 ± 9.1 mmHg at 1 month, 15.2 ± 7.0 mmHg at 6 months, and 14.2 ± 3.5 mmHg at 15 years. Surgical failures were significantly increased when preoperative IOP was high, and when severe complications occurred after AGV implantation (P < 0.05). Conclusion AGV implantation was successful for IOP control in patients with refractive glaucoma in the long term. However, the success rate of surgery decreased over time. Preoperative high IOP and severe complications related to the operation were significant risk factors for failure. PMID:29095931

Who should be admitted to the intensive care unit? The outcome of intensive care unit admission in stage IIIB-IV lung cancer patients.

PubMed

Kim, Yu Jung; Kim, Mi-Jung; Cho, Young-Jae; Park, Jong Sun; Kim, Jin Won; Chang, Hyun; Lee, Jeong-Ok; Lee, Keun-Wook; Kim, Jee Hyun; Yoon, Ho Il; Bang, Soo-Mee; Lee, Jae Ho; Lee, Choon-Taek; Lee, Jong Seok

2014-03-01

Critical care for advanced lung cancer patients is still controversial, and the appropriate method for the selection of patients who may benefit from intensive care unit (ICU) care is not clearly defined. We retrospectively reviewed the medical records of stage IIIB-IV lung cancer patients admitted to the medical ICU of a university hospital in Korea between 2003 and 2011. Of 95 patients, 64 (67%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2, and 79 (84%) had non-small-cell lung cancer. In total, 28 patients (30%) were newly diagnosed or were receiving first-line treatment, and 22 (23%) were refractory or bedridden. Mechanical ventilation was required in 85 patients (90%), and ICU mortality and hospital mortality were 57 and 78%, respectively. According to a multivariate analysis, a PaO2/FiO2 ratio<150 [odds ratio (OR)=5.51, 95% confidence interval (CI) 2.10-14.48, p=0.001] was independently associated with ICU mortality, and an ECOG PS≥2 (OR=9.53, 95% CI 2.03-44.85, p=0.004) and a need for vasoactive agents (OR=6.94, 95% CI 1.61-29.84, p=0.009) were independently associated with hospital mortality. Refractory or bedridden patients (n=22) showed significantly poorer overall survival (11.0 vs. 29.0 days, p=0.005). Among 21 patients who were discharged from the hospital, 11 (52%) received further chemotherapy. Certain advanced lung cancer patients may benefit from ICU management. However, refractory patients and patients with a poor PS do not seem to benefit from ICU care. Oncologists should try to discuss palliative care and end-of-life issues in advance to avoid futile care.

Evaluation of a haptics-based virtual reality temporal bone simulator for anatomy and surgery training.

PubMed

Fang, Te-Yung; Wang, Pa-Chun; Liu, Chih-Hsien; Su, Mu-Chun; Yeh, Shih-Ching

2014-02-01

Virtual reality simulation training may improve knowledge of anatomy and surgical skills. We evaluated a 3-dimensional, haptic, virtual reality temporal bone simulator for dissection training. The subjects were 7 otolaryngology residents (3 training sessions each) and 7 medical students (1 training session each). The virtual reality temporal bone simulation station included a computer with software that was linked to a force-feedback hand stylus, and the system recorded performance and collisions with vital anatomic structures. Subjects performed virtual reality dissections and completed questionnaires after the training sessions. Residents and students had favorable responses to most questions of the technology acceptance model (TAM) questionnaire. The average TAM scores were above neutral for residents and medical students in all domains, and the average TAM score for residents was significantly higher for the usefulness domain and lower for the playful domain than students. The average satisfaction questionnaire for residents showed that residents had greater overall satisfaction with cadaver temporal bone dissection training than training with the virtual reality simulator or plastic temporal bone. For medical students, the average comprehension score was significantly increased from before to after training for all anatomic structures. Medical students had significantly more collisions with the dura than residents. The residents had similar mean performance scores after the first and third training sessions for all dissection procedures. The virtual reality temporal bone simulator provided satisfactory training for otolaryngology residents and medical students. Copyright © 2013. Published by Elsevier Ireland Ltd.

System Architecture for Temporal Information Extraction, Representation and Reasoning in Clinical Narrative Reports

PubMed Central

Zhou, Li; Friedman, Carol; Parsons, Simon; Hripcsak, George

2005-01-01

Exploring temporal information in narrative Electronic Medical Records (EMRs) is essential and challenging. We propose an architecture for an integrated approach to process temporal information in clinical narrative reports. The goal is to initiate and build a foundation that supports applications which assist healthcare practice and research by including the ability to determine the time of clinical events (e.g., past vs. present). Key components include: (1) a temporal constraint structure for temporal expressions and the development of an associated tagger; (2) a Natural Language Processing (NLP) system for encoding and extracting medical events and associating them with formalized temporal data; (3) a post-processor, with a knowledge-based subsystem to help discover implicit information, that resolves temporal expressions and deals with issues such as granularity and vagueness; and (4) a reasoning mechanism which models clinical reports as Simple Temporal Problems (STPs). PMID:16779164

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome

PubMed Central

Raghunathan, V.; Sethi, S. K.; Dragon-Durey, M. A.; Dhaliwal, M.; Raina, R.; Jha, P.; Bansal, S. B.; Kher, V.

2017-01-01

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency. PMID:28356668

Street ketamine-associated bladder dysfunction: an emerging health problem.

PubMed

Lee, Py; Ong, Ta; Chua, Cb; Lei, Ccm; Teh, Gc

2009-01-01

Ketamine is frequently abused nowadays as a recreational drug. Case reports are emerging since 2007 to describe a new clinical entity of severe bladder dysfunction associated with chronic abuse of street ketamine. Severe lower urinary tract symptoms of urinary frequency and urgency which are refractory to conventional treatment. Quality of life is adversely affected as a consequence. Chronic kidney disease will develop in advanced cases. Investigation findings: The urine is sterile on culture. Ultrasound will show reduced bladder capacity with thickened bladder wall. In advanced stage, hydronephrosis and renal impairment will develop. Patients should be advised to stop street ketamine use immediately. Anticholinergic medication could be tried to alleviate the symptoms. Refractory cases with dilatation of the upper urinary tract might need urinary diversion. Awareness of this new condition is essential in diagnosis. Early intervention offers better treatment outcome.

Functional Disorders of Constipation: Paradoxical Puborectalis Contraction and Increased Perineal Descent

PubMed Central

Payne, Isaac; Grimm, Leander M.

2017-01-01

Paradoxical puborectalis contraction (PPC) and increased perineal descent (IPD) are subclasses of obstructive defecation. Often these conditions coexist, which can make the evaluation, workup, and treatment difficult. After a thorough history and examination, workup begins with utilization of proven diagnostic modalities such as cinedefecography and anal manometry. Advancements in technology have increased the surgeon's diagnostic armamentarium. Biofeedback and pelvic floor therapy have proven efficacy for both conditions as first-line treatment. In circumstances where PPC is refractory to biofeedback therapy, botulinum toxin injection is recommended. Historically, pelvic floor repair has been met with suboptimal results. In IPD, surgical therapy now is directed toward the potentially attendant abnormalities such as rectoanal intussusception and rectal prolapse. When these associated abnormalities are not present, an ostomy should be considered in patients with IPD as well as medically refractory PPC. PMID:28144209

Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or adverse effect of vagal nerve stimulation?

PubMed

Akman, Cigdem; Riviello, James J; Madsen, Joseph R; Bergin, Ann M

2003-06-01

Sensory symptoms are commonly seen in association with focal epilepsy, but viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main clinical manifestation. With the introduction of vagal nerve stimulation (VNS) for medically refractory epilepsy, viscerosensory symptoms commonly occur as an adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local neck or throat pain, and cough are the most common adverse effects seen during active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a tingling sensation of the neck and throat is directly related to stimulation intensity. We present a case in which recurrent pharyngeal sensations caused a diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and correlating this with clinical symptoms helped determine the etiology of the recurrent sensory symptoms.

Pre- and post-operative Wisconsin card sorting test performance in patients with temporal lobe epilepsy due to hippocampal sclerosis

PubMed Central

Tisser, Luciana; Palmini, Andre; Paglioli, Eliseu; Portuguez, Mirna; Azambuja, Ney; da Costa, Jaderson Costa; Paglioli, Eduardo; Torres, Carolina; Martinez, Jose Victor

2007-01-01

Patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE/HS) have a distinct neuropsychological profile, but there is still debate on whether executive dysfunction is part of this profile and also whether temporal lobe surgery can modify this dysfunction. Objective To study the presence and reversibility of executive dysfunction in patients with unilateral TLE/HS. Methods Twenty-five patients with refractory seizures due to TLE/HS underwent presurgical evaluation which included the application of the Wiconsin Card Sorting Test (WCST). Nineteen were re-evaluated in follow up, at least 6 months after selective amygdalo-hippocampectomy (SAH). Twenty-two control subjects matched for age and education also performed the WCST. Results Sixteen of the 25 patients (64%) completed fewer than four categories in the WCST whereas only 4 of the 22 controls (18%) did not complete at least four categories (p<0.005). In addition, the performance of the patients involved significantly more perseverative responses and errors compared to controls. The patient group demonstrated significant post-operative improvement in many measures of the WCST following SAH. Conclusions These findings support the presence of executive dysfunction in patients with TLE/HS and suggest that such dysfunction can be partially reversed by selective resection of epileptogenic mesial temporal structures. PMID:29213385

Representing and querying now-relative relational medical data.

PubMed

Anselma, Luca; Piovesan, Luca; Stantic, Bela; Terenziani, Paolo

2018-03-01

Temporal information plays a crucial role in medicine. Patients' clinical records are intrinsically temporal. Thus, in Medical Informatics there is an increasing need to store, support and query temporal data (particularly in relational databases), in order, for instance, to supplement decision-support systems. In this paper, we show that current approaches to relational data have remarkable limitations in the treatment of "now-relative" data (i.e., data holding true at the current time). This can severely compromise their applicability in general, and specifically in the medical context, where "now-relative" data are essential to assess the current status of the patients. We propose a theoretically grounded and application-independent relational approach to cope with now-relative data (which can be paired, e.g., with different decision support systems) overcoming such limitations. We propose a new temporal relational representation, which is the first relational model coping with the temporal indeterminacy intrinsic in now-relative data. We also propose new temporal algebraic operators to query them, supporting the distinction between possible and necessary time, and Allen's temporal relations between data. We exemplify the impact of our approach, and study the theoretical and computational properties of the new representation and algebra. Copyright © 2018 Elsevier B.V. All rights reserved.

Pevonedistat and Ibrutinib in Treating Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-20

B-Cell Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; Richter Syndrome

Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

ClinicalTrials.gov

2017-07-14

Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory

Role of ictal baseline shifts and ictal high-frequency oscillations in stereo-electroencephalography analysis of mesial temporal lobe seizures.

PubMed

Wu, Shasha; Kunhi Veedu, Hari Prasad; Lhatoo, Samden D; Koubeissi, Mohamad Z; Miller, Jonathan P; Lüders, Hans O

2014-05-01

To assess the role of ictal baseline shifts (IBS) and ictal high-frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS). We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy-five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs. IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty-seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive pole at the posterior/lateral part of the A-H complex. The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Organizational fidelity to a medication management evidence-based practice in the treatment of schizophrenia.

PubMed

El-Mallakh, Peggy; Howard, Patricia B; Rayens, Mary Kay; Roque, Autumn P; Adkins, Sarah

2013-11-01

Organizational support is essential for successful implementation of evidence-based practice (EBP) in clinical settings. This 3-year study used a mixed qualitative and quantitative design to implement a medication management EBP in the treatment of schizophrenia in six community mental health clinics in a south-central state of the United States. Findings from organizational fidelity assessments indicate that support for EBP implementation was moderate. Organizational support was highest for prescriber access to relevant patient information at each medication visit, scheduling flexibility for patients' urgent problems, and availability of medication guidelines. Organizational support was lowest for medication availability and identification of treatment refractory patients. Findings suggest that leadership is essential to support successful implementation. Nurse educators can incorporate implementation research and leadership training into graduate nursing programs to facilitate successful EBP implementation in practice settings. Copyright 2013, SLACK Incorporated.

Impact of ranolazine on clinical outcomes and healthcare resource utilization in patients with refractory angina pectoris.

PubMed

Ling, Hua; Packard, Kathleen A; Burns, Tammy L; Hilleman, Daniel E

2013-12-01

Ranolazine is a novel antianginal medication approved for the treatment of chronic angina. There are only limited data concerning the efficacy of ranolazine in reducing healthcare resource utilization in patients with refractory angina pectoris. The primary objective of this analysis was to evaluate the efficacy and safety of ranolazine in refractory angina pectoris. In addition, the impact of ranolazine on healthcare resource utilization was assessed. Consecutive patients with refractory angina pectoris treated with ranolazine at two cardiology practices in the state of Nebraska were included in this analysis. The Canadian Cardiovascular Society (CCS) angina class and frequency and type of healthcare resource consumption were determined during the 12 months prior to and the 12 months after initiation of ranolazine. A total of 150 pts (64 % men) with a mean age of 66 ± 12 years were included in this analysis. All patients had previously undergone coronary revascularization. Nitrates, β-adrenoceptor antagonists (β-blockers), and calcium antagonists (calcium channel blockers) were being used in 83, 97, and 75 % of patients, respectively. During ranolazine treatment, a significant improvement in CCS angina class was observed, with 23 patients improving by one class and no patient experiencing a deterioration in functional class (p = 0.025). A total of 53 side effects occurred in 28 (19 %) patients receiving ranolazine. Of those patients with side effects, four required dose reduction and seven required drug discontinuation. The frequency of clinic visits and emergency room visits was lower during ranolazine treatment, but the differences in frequency were not significant. The number of patients hospitalized and the number of hospitalizations were significantly lower during ranolazine therapy than in the pre-ranolazine study period (p = 0.002). Ranolazine improved the CCS angina class and reduced hospitalizations over a 12-month follow-up period in a group of patients with difficult-to-treat refractory angina pectoris.

Tuberous Sclerosis with Epilepsy

DTIC Science & Technology

2009-02-01

seizures. She uses a vagal nerve stimulator (VNS) set at maximum level, and she is maintained on a modified ketogenic diet to help control seizure...refractory to medical treatment include ketogenic diet or VNS. The anticonvulsant effects of the ketogenic diet are a result of the persistent state of...patient’s situation improved seizure control was achieved with a combination of a modified ketogenic diet , VNS, and depot medroxyprogesterone acetate

Case Report. Prevention of Clozapine-Induced Granulocytopenia/Agranulocytosis with Granulocyte-Colony Stimulating Factor (G-CSF) in an Intellectually Disabled Patient with Schizophrenia

ERIC Educational Resources Information Center

Rajagopal, G.; Graham, J. G.; Haut, F. F. A.

2007-01-01

Background: While clozapine is an effective treatment for refractory schizophrenia, its use is limited by haematological side effects. Treatment options that allow continued prescription of clozapine by tackling these side effects will greatly aid patients for whom this medication is all too often their only hope of recovery. Method: In this case…

Successful treatment of severe pouchitis with rebamipide refractory to antibiotics and corticosteroids: A case report

PubMed Central

Miyata, Mitsuki; Konagaya, Toshihiro; Kakumu, Shiniti; Mori, Takeshi

2006-01-01

The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this report, we have described a successful treatment of severe refractory pouchitis with a novel agent, rebamipide, known to promote epithelial cell regeneration and angiogenesis. A 27-year-old male with ileo-anal pouch surgery presented with worsening anal pain, diarrhea, and abdominal pain. The patient was diagnosed to have pouchitis and was given metronidazole together with betamethasone enema (3.95 mg/dose). However, despite this intensive therapy, the patient did not improve. On endoscopy, ulceration and inflammation were seen in the ileal pouch together with contact bleeding and mucous discharge. The patient was treated with rebamipide enema (150 mg/dose) twice a day for 8 wk without additional drug therapy. Two weeks after the rebamipide therapy, stool frequency started to decrease and fecal hemoglobin became negative at the 4th wk. At the end of the therapy, endoscopy revealed that ulcers in the ileal pouch had healed with no obvious inflammation. The effect of rebamipide enema was dramatic and was maintained throughout the 11-mo follow-up. The patient continued to be in remission. No adverse effects were observed during the treatment or the follow-up period. The sustained response seen in this case with severe and refractory pouchitis indicates that agents, which promote epithelial cell growth, angiogenesis and mucosal tissue regeneration, are potential therapeutic agents for the treatment of refractory colorectal lesions. PMID:16489687

Refractory chronic migraine: is drug withdrawal necessary before starting a therapy with onabotulinum toxin type A?

PubMed

Butera, Calogera; Colombo, Bruno; Bianchi, Francesca; Cursi, Marco; Messina, Roberta; Amadio, Stefano; Guerriero, Roberta; Comi, Giancarlo; Del Carro, Ubaldo

2016-10-01

Onabotulinum toxin A (BT-A) is now one of the authorized prophylaxis treatments for chronic migraine (CM) thanks to previous clinical trials, which usually required a pharmacologic washout as a precondition for demonstrating its efficacy. Aim of our study was to assess the efficacy in daily clinical practice of BT-A injections in refractory CM patients, regardless of medication overuse without any standardized withdrawal protocol and without stopping the ongoing prophylaxis treatment as well. We treated 44 refractory CM patients (37 females and 7 males) trimonthly without any modification in symptomatic, or prophylactic drug therapy. Main efficacy variables included number of headache, or migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12-, 24-, and 36-week follow-up. All variables showed a statistically significant improvement at week 36. In general, more than 50 % of patients had a good clinical outcome (including all improved patients, either partial or full responder) and that the percentage of drug abuser patients significantly decreased from 75 to 50 %, thanks to a spontaneous reduction of the symptomatic drug intake. Adverse events were uncommon and did not require treatment discontinuation. Onabotulinum toxin A treatment in refractory CM patients with unsatisfactory prophylactic drug treatments and pharmacological abuse is effective in improving clinical outcome and quality of life. This result may be achieved through a flexible pharmacologic approach tailored to each patient's needs; moreover, the patient himself can be often expected to reduce drug consumption spontaneously.

Comparison of Efficacy Between Endoscopic Cyclophotocoagulation and Alternative Surgeries in Refractory Glaucoma

PubMed Central

Yang, Yangfan; Zhong, Jing; Dun, Zhongjun; Liu, Xiao-an; Yu, Minbin

2015-01-01

Abstract Refractory glaucoma refers to uncontrolled intraocular pressure (IOP) despite anti-glaucoma medication and surgical treatment, which remains a challenge to be treated. The objective of this study is to evaluate and statistically compare the clinical efficacy between endoscopic cyclophotocoagulation (ECP) and alternative surgical techniques in the treatment of refractory glaucoma in this article, as a meta-analysis. Data sources are China Biomedical Database (Sinomed, online version), China National Knowledge Infrastructure (CNKI), Cqvip, Wanfang database, and PubMed. The randomized controlled trial (RCT) and case–control study literatures evaluating the clinical efficacy between ECP and other surgical techniques were searched electronically from public databases. The methodology quality of the retrieved articles was evaluated according to the RCT or case–control study criteria. The success rate of treatment, intraocular pressure (IOP) and visual acuity were statistically compared. RevMan 5.3 software was used for the meta-analysis. In total, 6 relevant control studies were selected in this study with a total sampling of 429 cases (429 eyes), including 204 eyes in the ECP group and 225 in the non-ECP group. Meta-analysis demonstrated that the clinical efficacy did not significantly differ between 2 groups (P > 0.05). Postoperative IOP was dramatically reduced in both groups. However, it was difficult to evaluate the combined influence of ECP and non-ECP therapies upon IOP reduction. In conclusion, ECP and non-ECP treatment yielded almost equivalent clinical efficacy in treating refractory glaucoma. The IOP-lowering degree, safety, and incidence of complications remain to be further elucidated by RCTs with a larger sample size. PMID:26426659

Super-refractory status epilepticus in West China.

PubMed

Tian, L; Li, Y; Xue, X; Wu, M; Liu, F; Hao, X; Zhou, D

2015-07-01

This study aims to determine the general frequency, mortality, and risk factors of super-refractory status epilepticus (SRSE) versus non-refractory status epilepticus (NRSE) and refractory status epilepticus (RSE). This work is a retrospective study. Clinical data of patients who were diagnosed with status epilepticus (SE) in the neurological ward and neuro-intensive care unit of West China Hospital from January 2009 to December 2012 were collected and analyzed. A total of 98 patients were included in the study. The percentages of NRSE, RSE, and SRSE were 67.3%, 20.4%, and 12.2%, respectively. Convulsive SE was the main seizure type among the three groups. The most common cause of NRSE was related to epilepsy (EP). However, 67.7% of SRSE cases were caused by acute encephalitis. Moreover, 47% of SE and 40% of RSE cases had a history of EP, whereas only 8.3% of SRSE cases had such history (P < 0.01). The percentage of patients with STESS ≤2 was lowest in the SRSE group without statistical significance (P > 0.05). The general mortality of SE was 7.1%, whereas that of SRSE was 50%. During follow-up, most SRSE patients who survived have developed symptomatic EP. This study was the first to use the statistical percentage of SRSE. Approximately 12.2% of SE cases will result in SRSE, which is a challenging medical situation for doctors. Patients with first episodes and acute encephalitis were also prone to develop SRSE. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clozapine for Drug-Refractory Irritability in Individuals with Developmental Disability.

PubMed

Wink, Logan K; Badran, Ismail; Pedapati, Ernest V; Sorensen, Rena; Benton, Stacy C; Johnson, Mark C; Wissel, Gregory; Erickson, Craig A

2016-11-01

In this case series, we describe the acute clinical impact and tolerability of rapid titration of clozapine for treatment of refractory irritability in five hospitalized youth with developmental disability. We offer this descriptive report in an effort to expand the evidence base guiding treatment of refractory aggression in this population. Five youth with developmental disability and severe irritability were admitted to a 10-bed psychiatric crisis stabilization unit where they received thorough psychiatric and medical evaluation. Informed consent was obtained in each case, and each patient underwent rapid titration onto clozapine. Clozapine monitoring guidelines were followed for all patients throughout treatment, and clinical severity at baseline and improvement with treatment was measured by use of the Clinical Global Impressions-Severity scale (CGI-S) and the Clinical Global Impressions-Improvement scale (CGI-I). One female and four males diagnosed with developmental disability and at least one other psychiatric diagnosis, mean age of 13.1 ± 2.1 years, and mean CGI-S at baseline of 5.8, each received clozapine treatment by rapid titration. The mean therapeutic total daily dose of clozapine was 380 ± 200 mg. All patients demonstrated acute clinical improvement with the mean final CGI-I of 2.0, or "much improved." These initial results support the potential utility of clozapine rapid titration for treatment of severe refractory irritability in youth with developmental disability. These patients tolerated clozapine treatment in the short term. Future studies are needed to thoroughly evaluate the long-term safety of clozapine treatment in this population.

Management of refractory trigeminal neuralgia using extended duration pulsed radiofrequency application.

PubMed

Thapa, Deepak; Ahuja, Vanita; Dass, Christopher; Verma, Parul

2015-01-01

Trigeminal neuralgia (TN) produces incapacitating facial pain that reduces quality of life in patients. Thermal radiofrequency (RF) ablation of gasserian ganglion (GG) is associated with masseter weakness and unpleasant sensations along the distribution of the ablated nerve. Pulsed radiofrequency (PRF) of GG has minimal side effects but literature is inconclusive regarding its benefit in refractory TN. Increasing the duration of PRF application to 6 minutes in TN produced encouraging results. PRF application to the saphenous nerve for 8 minutes reported improved pain relief and patient satisfaction. We report successful management of two patients of classic TN, which were refractory to medical management and interventional nerve blocks. The lesion site were confirmed with motor and sensory stimulation through a 22 G, 10 cm RF needle with 5 mm active tip. Both the patients received four cycles of PRF at 42 °C with each cycle of 120 seconds (8 minutes). The visual analogue scale (VAS) in case 1 reduced from pre-block score of 80 to score 10 post-block, while in case 2 the VAS reduced from pre-block score of 85 to score 15 post-block. During follow up both the patients are now pain free with minimal dose of carbamazepine at 12 and 6 months respectively. We used PRF for longer duration (8 minutes) in these patients, which resulted in improved VAS and WHOQOL-BREF score in these patients. PRF of mandibular division of GG for extended duration provided long-term effective pain relief and quality of life in patients of refractory classic TN.

Surgical Outcomes of Additional Ahmed Glaucoma Valve Implantation in Refractory Glaucoma.

PubMed

Ko, Sung Ju; Hwang, Young Hoon; Ahn, Sang Il; Kim, Hwang Ki

2016-06-01

To evaluate the surgical outcomes of the implantation of an additional Ahmed glaucoma valve (AGV) into the eyes of patients with refractory glaucoma following previous AGV implantation. This study is a retrospective review of the clinical histories of 23 patients who had undergone a second AGV implantation after a failed initial implantation. Age, sex, prior surgery, glaucoma type, number of medications, intraocular pressure (IOP), visual acuity, and surgical complications were analyzed. Surgical success was defined as IOP maintained below 21 mm Hg, with at least a 20% overall reduction in IOP, regardless of the use of IOP-lowering medications. Following the implantation of a second AGV, the mean IOP decreased from 39.3 to 18.5 mm Hg (52.9% reduction, P<0.001). The mean number of postoperative IOP-lowering medications administered decreased from 2.8 to 1.7 after the second AGV implantation (P<0.001). The cumulative probability of success for the procedure was 87% after 1 year and 52% after 3 years. Three patients (13.0%) experienced bullous keratopathy after the second AGV implantation. None of the patients showed any evidence of diplopia or ocular movement limitation as a result of the presence of 2 AGVs in the same eye. Prior trabeculectomy was found to be a significant risk factor for failure (P=0.027). A second AGV implantation can be a good choice of surgical treatment when the first AGV has failed to control IOP.

Endolymphatic Sac Decompression With Intra-Sac Dexamethasone Injection in Menière's Disease.

PubMed

Bojrab, Dennis I; LaRouere, Michael J; Bojrab, Dennis I; Babu, Seilesh C; Sargent, Eric W; Chan, Eleanor Y; Hong, Robert S

2018-06-01

Endolymphatic sac decompression surgery (ELSD) may be used to treat patients who have Menière's 's disease refractory to medical therapy. In this study, we investigated whether or not the injection of steroid into the endolymphatic sac at the time of ELSD provides additional benefit to patient outcomes. Randomized prospective single-blinded placebo-controlled study. Tertiary center. Patients with Menière's disease with poorly controlled vertigo despite medical therapy and serviceable hearing that were offered ELSD. Patients randomized into two groups, with control group (n = 17) undergone ELSD without steroid injection and experimental group undergone ELSD with steroid injection (n = 18) MAIN OUTCOME MEASURE(S):: Audiogram, dizziness handicap inventory, tinnitus handicap inventory, frequency of vertigo spells, functional level scale, and quality of life were obtained at multiple intervals from preoperatively to 24 months postoperatively. ELSD resulted in a statistically significant improvement in vertigo control whether or not steroid was injected into the endolymphatic sac at the time of surgery. However, no additional benefit was observed with the addition of intra-sac steroid injection. No statistical difference in pure-tone average, tinnitus handicap inventory, dizziness handicap inventory, or quality of life was observed between the steroid and nonsteroid surgical groups up to 24 months postoperatively. ELSD is an effective treatment for Menière's disease refractory to medical therapy; however, the addition of intra-sac steroid injection at the time of surgery does not seem to result in a further improvement in patient outcomes.

Chemical composition of wildland and agricultural biomass burning particles measured downwind during the BBOP study

NASA Astrophysics Data System (ADS)

Onasch, T. B.; Shilling, J. E.; Wormhoudt, J.; Sedlacek, A. J., III; Fortner, E.; Pekour, M. S.; Chand, D.; Zhou, S.; Collier, S.; Zhang, Q.; Kleinman, L. I.; Lewis, E. R.; Yokelson, R. J.; Adachi, K.; Buseck, P. R.; Freedman, A.; Williams, L. R.

2017-12-01

The Biomass Burning Observation Project (BBOP), a Department of Energy (DOE) sponsored study, measured emissions from wildland fires in the Pacific Northwest and agricultural burns in the Central Southeastern US from the DOE Gulfstream-1 airborne platform over a four month period in 2013. Rapid physical, chemical and optical changes in biomass burning particles were measured downwind (< 3 hours temporally) from wildland fires. The chemical composition of the particulate emissions was characterized using an Aerodyne Soot Particle Aerosol Mass Spectrometer (SP-AMS) and a Single Particle Soot Photometer (SP2) and the measurement results will be presented in the context of the fire location, combustion conditions, and optical property measurements, including extinction and single scattering albedos. The SP-AMS was operated with both laser and resistively heated tungsten vaporizers, alternating between laser on and off. With the laser vaporizer off, the instrument operated as a standard high resolution AMS. Under these sampling conditions, the non-refractory chemical composition, including the level of oxidation (i.e., O:C, H:C, and organic mass/organic carbon ratios, OM:OC), of the biomass burning particles was characterized as a function of the fuel type burned, modified combustion efficiency, and degree of oxidation during downwind transport. With the laser vaporizer on, the SP-AMS was also sensitive to the refractory black carbon (rBC) content, in addition to the non-refractory components. The chemical measurements will be correlated with simultaneous optical measurements. We will also present preliminary results from laboratory studies on tar balls and SP-AMS OA quantification while operating with both laser and tungsten vaporizers.

Real-time fMRI neurofeedback to down-regulate superior temporal gyrus activity in patients with schizophrenia and auditory hallucinations: a proof-of-concept study.

PubMed

Orlov, Natasza D; Giampietro, Vincent; O'Daly, Owen; Lam, Sheut-Ling; Barker, Gareth J; Rubia, Katya; McGuire, Philip; Shergill, Sukhwinder S; Allen, Paul

2018-02-12

Neurocognitive models and previous neuroimaging work posit that auditory verbal hallucinations (AVH) arise due to increased activity in speech-sensitive regions of the left posterior superior temporal gyrus (STG). Here, we examined if patients with schizophrenia (SCZ) and AVH could be trained to down-regulate STG activity using real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF). We also examined the effects of rtfMRI-NF training on functional connectivity between the STG and other speech and language regions. Twelve patients with SCZ and treatment-refractory AVH were recruited to participate in the study and were trained to down-regulate STG activity using rtfMRI-NF, over four MRI scanner visits during a 2-week training period. STG activity and functional connectivity were compared pre- and post-training. Patients successfully learnt to down-regulate activity in their left STG over the rtfMRI-NF training. Post- training, patients showed increased functional connectivity between the left STG, the left inferior prefrontal gyrus (IFG) and the inferior parietal gyrus. The post-training increase in functional connectivity between the left STG and IFG was associated with a reduction in AVH symptoms over the training period. The speech-sensitive region of the left STG is a suitable target region for rtfMRI-NF in patients with SCZ and treatment-refractory AVH. Successful down-regulation of left STG activity can increase functional connectivity between speech motor and perception regions. These findings suggest that patients with AVH have the ability to alter activity and connectivity in speech and language regions, and raise the possibility that rtfMRI-NF training could present a novel therapeutic intervention in SCZ.

Neuronal zinc-α2-glycoprotein is decreased in temporal lobe epilepsy in patients and rats.

PubMed

Liu, Ying; Wang, Teng; Liu, Xi; Wei, Xin; Xu, Tao; Yin, Maojia; Ding, Xueying; Mo, Lijuan; Chen, Lifen

2017-08-15

Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used. The existence and level of ZAG in the brain were identified using immunohistochemistry, double-labeled immunofluorescence and western blot, and the expression level of AZGP1 mRNA was determined with quantitative real-time polymerase chain reaction (qrt-PCR). To explore the potential biological role of ZAG in the brain, co-immunoprecipitation (Co-IP) of phosphorylated ERK (p-ERK), TGF-β1 and ZAG was also performed. ZAG was found in the cytoplasm of neurons in brain tissue from both patients and rats. The levels of AZGP1 mRNA and ZAG were lower in refractory TLE patients and PTZ-kindled rats than in controls. In addition, the ZAG level decreased as PTZ kindling continued. Co-IP identified direct binding between p-ERK, TGF-β1 and ZAG. ZAG was found to be synthesized in neurons, and both the AZGP1 mRNA and ZAG protein levels were decreased in epilepsy patients and rat models. The reduction in ZAG may participate in the pathogenesis and pathophysiology of epilepsy by interacting with p-ERK and TGF-β1, promoting inflammation, regulating the metabolism of ketone bodies, or affecting other epilepsy-related molecules. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Laparoscopic Reversal of Roux-en-Y Gastric Bypass: Technique and Utility for Treatment of Endocrine Complications

PubMed Central

Campos, Guilherme M.; Ziemelis, Martynas; Paparodis, Rodis; Ahmed, Muhammed; Davis, Dawn Belt

2018-01-01

Background The anatomical and physiological changes with Roux-en-Y gastric bypass (RYGB) may lead to uncommon but occasionally difficult to treat complications such as hyperinsulinemic hypoglycemia with neuroglycopenia and recalcitrant hypocalcemia associated to hypoparathyroidism. Medical management of these complications is challenging. Laparoscopic reversal of RYGB anatomy with restoration of pyloric function and duodenal continuity is a potential treatment. Objective To present the indications, surgical technique and clinical outcomes of laparoscopic reversal of RYGB. Setting Tertiary Academic Medical Center, United States. Methods Prospective study of consecutive patients offered laparoscopic reversal of RYGB. Results Five patients with remote laparoscopic RYGB underwent laparoscopic reversal of RYGB to normal anatomy (n=2) or modified sleeve gastrectomy (n=3). Indications were medically refractory hyperinsulinemic hypoglycemia with neuroglycopenia (n=3), recalcitrant hypocalcemia with hypoparathyroidism (n=1) and both conditions simultaneously (n=1). Prior to reversal all patients had a gastrostomy tube placed in the excluded stomach to document improvement of symptoms. Laparoscopic reversal was accomplished successfully in all patients. Three post-operative complications occurred; bleeding that required transfusion, gallstone pancreatitis and a superficial trocar site infection. Average length of stay was 3 days. At a mean follow-up of 12 months (range 3 to 22), no additional episodes of neuroglycopenia occurred, average number of hypoglycemic episodes per week decreased from 18.5±12.4 to 1.5±1.9 (p=0.05) and hypocalcemia became responsive to oral replacement therapy in both patients. Conclusions Laparoscopic reversal of RYGB to normal anatomy or modified sleeve gastrectomy is feasible and may be a therapeutic option for selected patients with medically refractory hyperinsulinemic hypoglycemia and/or recalcitrant hypocalcemia associated to hypoparathyroidism. PMID:24120983

Bleb Analysis and Short-Term Results of Biodegradable Collagen Matrix-Augmented Ahmed Glaucoma Valve Implantation: 6-Month Follow-up.

PubMed

Rho, Seungsoo; Sung, Youngje; Ma, Kyoung Tak; Rho, Sae Heun; Kim, Chan Yun

2015-09-01

To evaluate the short-term efficacy of a biodegradable collagen matrix (BCM) as an adjuvant for Ahmed valve implantation surgery to prevent the hypertensive phase. This prospective study included 43 refractory glaucoma eyes, all followed for 6 months. Refractory glaucoma was defined as an IOP higher than 20 mm Hg with antiglaucoma eye drops without previous glaucoma surgery. Conventional method was performed in 21 eyes and BCM-augmented Ahmed valve implantation (BAAVI) in 22 eyes. In the BAAVI group, a 10 × 10 × 2-mm BCM was sutured on an Ahmed glaucoma valve FP7 model. Complete success was defined as an IOP of 21 mm Hg or lower (target IOP 1) or 17 mm Hg or lower (target IOP 2) without antiglaucoma medications and qualified success as an IOP of 21 mm Hg or lower with or without medications. Maximal bleb thickness was measured using anterior segment optical coherence tomography images. The preoperative IOPs and numbers of preoperative antiglaucoma medications were similar for both groups. Complete target IOP 1 success rates were 38.1% and 86.4%, complete target IOP 2 success rates were 19.0% and 59.1%, and qualified success rates were 52.4% and 90.9% in the conventional and BAAVI groups, respectively (P < 0.05). The hypertensive phase rate was lower in the BAAVI group (4.5% vs. 47.6%, P = 0.002). Maximal bleb thickness was increased in the BAAVI group on postoperative days 30 and 180 (P < 0.05). Success rates were higher in the BAAVI group than in the conventional group with the change of bleb morphology. Furthermore, use of BCM significantly decreased the need for antiglaucoma medications for at least 6 months postoperatively.

Outcomes of Ahmed Valve Implant Following a Failed Initial Trabeculotomy and Trabeculectomy in Refractory Primary Congenital Glaucoma

PubMed Central

Dave, Paaraj; Senthil, Sirisha; Choudhari, Nikhil; Sekhar, Garudadri Chandra

2015-01-01

Purpose: The aim was to report the outcome of Ahmed glaucoma valve (AGV) (New World Medical, Inc., Rancho Cucamonga, CA, USA) implantation as a surgical intervention following an initial failed combined trabeculotomy + trabeculectomy (trab + trab) in refractory primary congenital glaucoma (RPCG). Materials and Methods: Retrospective chart review of 11 eyes of 8 patients who underwent implantation of AGV (model FP8) for RPCG between 2009 and 2011. Prior trab + trab had failed in all the eyes. Success was defined as an intraocular pressure (IOP) >5 and ≤ 18 mmHg during examination under anesthesia with or without medications and without serious complications or additional glaucoma surgery. Results: The mean age at AGV implantation was 15.4 ± 4.9 months. The mean preoperative IOP was 28 ± 5.7 mmHg which reduced to 13.6 ± 3.4 mmHg postoperatively at the last follow-up (P < 0.0001). The number of topical antiglaucoma medications reduced from a mean of 2.6 ± 0.5 to 1.6 ± 0.9 postoperatively (P = 0.009). The definition of qualified success was met in 10 (90%) eyes. One eye developed a shallow anterior chamber with choroidal detachment at 1-week, which resolved spontaneously with medications. None of the eyes developed a hypertensive phase. One eye had a long tube resulting in tube corneal touch that required trimming of the tube. One eye developed tube retraction, which was treated with a tube extender. The mean follow-up was 17.9 ± 9.3 (6.2-35.4) months. Conclusion: Managing RPCG remains a challenge. AGV implant was successful in a significant proportion of cases. PMID:25624676

Combined Phacoemulsification and Ahmed Glaucoma Drainage Implant Surgery for Patients With Refractory Glaucoma and Cataract.

PubMed

Valenzuela, Felipe; Browne, Andrew; Srur, Miguel; Nieme, Carlos; Zanolli, Mario; López-Solís, Remigio; Traipe, Leonidas

2016-02-01

To examine the indications, safety, efficacy, and complications of combined phacoemulsification and Ahmed glaucoma drainage implant surgery. A retrospective case review of 35 eyes (31 patients) subjected to combined phacoemulsification and Ahmed glaucoma drainage implant surgery. Demographic characteristics of the study population, indications for combined surgery, and operative and postoperative complications were recorded. Visual acuity, intraocular pressure (IOP), and number of glaucoma medications were evaluated preoperatively and postoperatively. Complete success was defined as IOP ≤ 21 mm Hg without medication, qualified success if IOP ≤ 21 mm Hg with ≥ 1 medications, and failure if IOP>21 mm Hg or ≤ 5 mm Hg on ≥ 2 consecutive visits. Mean follow-up was 29.5 months (range, 6 to 87 mo). The most common indication for combined surgery was a history of prior failed trabeculectomy (60%). Postoperative visual acuity improved in 30 of 35 eyes (85%) (P<0.01) regardless of the indication for combined surgery. IOP was reduced from a mean of 24.7 to 15.0 mm Hg at the last follow-up visit (P<0.01). The number of IOP-lowering medications was reduced from a median of 3.1 preoperatively to 1.7 at the last follow-up (P<0.01). Overall, there were 31 eyes (89%) classified as qualified success and 4 eyes (11%) as complete success. The most common postoperative complication was a hypertensive phase in 18 eyes (51%). Combined phacoemulsification and Ahmed glaucoma drainage implant surgery seems to be a safe and effective surgical option, providing good visual rehabilitation and control of IOP for patients with refractory glaucoma and cataract.

[Towards a better use of midazolam in end of life: A survey in a department of medical oncology].

PubMed

Beneton, Aurélie; Vallard, Alexis; Brosse, Christelle; Poenou, Géraldine; Pacaut, Cécile; Magné, Nicolas; Morisson, Stéphanie

2017-11-01

At the end of life of cancer patients, sedation is sometimes needed, in order to palliate unbearable symptoms that other treatments fail to relieve. Midazolam is currently recommended for sedation and its prescription is guided by national guidelines. The aim of the present study was to evaluate the practices of midazolam prescription in a department of medical oncology and to compare the results with French national recommendations in order to improve the midazolam use in case of sedation. We conducted a retrospective survey studying midazolam prescriptions in patients who died between 2014 and 2015 in the medical oncology department. Compliance rates with recommendations were reviewed. A total of 99 medical files were analyzed. Fifty-three patients received midazolam: 64.4% for refractory symptoms, 22% for anxiolyse, 10.2% for acute respiratory distress syndrome. When reported, the titration indications and modalities systematically conformed to guidelines. In case of sedation for refractory symptoms, adherence to guidelines was 76% regarding the family information, 63% regarding the patient information, 61% regarding the collegial nature of the initiation decision, 34% regarding the titration achievement and 5% regarding the pluridisciplinary nature of the initiation decision. Although limited justifications in midazolam prescriptions could have resulted in an overestimate of sedation and in an underestimate of titrations, current guideline are not enough applied in routine, especially regarding the necessity of a pluridisciplinary decision-making. A list of requirements before midazolam initiation is suggested, to increase the adherence to guidelines. Our results highlight the necessity of a better midazolam use in life-end sedations. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Perirhinal cortex and temporal lobe epilepsy

PubMed Central

Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

2013-01-01

The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

Treatment of absolute painful glaucoma with dynamic arcs using novalis shaped beam radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez-Olhovich, Irene; Celis, Miguel Angel; Larraga-Gutierrez, Jose

2006-11-15

Purpose: We assessed the effect of shaped beam conformal stereotactic radiosurgery (SRS) in 1 patient with chronic painful glaucoma in one eye refractory to medical treatment. Methods and Materials: Left eye ciliary body was targeted at 18 Gy (90% isodose curve) with a dedicated linear accelerator (Novalis, BrainLAB, Germany) SRS. Interval follow-up was performed weekly for the first month, and every 2 months until 1 year was completed with clinical examinations and intraocular pressure (IOP) measurements. Results: Ocular pain resolved at 6 weeks after SRS treatment. IOP decreased and normalized at 1 year. Conclusions: We present a case in whichmore » SRS appears to be an effective treatment of chronic refractory painful glaucoma. Further Phase I studies are needed to know the best parameters for radiation dose, tolerance of organs at risk, and pathophysiologic effects.« less

Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK).

PubMed

Heaney, Liam G; Djukanovic, Ratko; Woodcock, Ashley; Walker, Samantha; Matthews, John G; Pavord, Ian D; Bradding, Peter; Niven, Robert; Brightling, Chris E; Chaudhuri, Rekha; Arron, Joseph R; Choy, David F; Cowan, Douglas; Mansur, Adel; Menzies-Gow, Andrew; Adcock, Ian; Chung, Kian F; Corrigan, Chris; Coyle, Peter; Harrison, Timothy; Johnston, Sebastian; Howarth, Peter; Lordan, James; Sabroe, Ian; Bigler, Jeannette; Smith, Dirk; Catley, Matthew; May, Richard; Pierre, Lisa; Stevenson, Chris; Crater, Glenn; Keane, Frank; Costello, Richard W; Hudson, Val; Supple, David; Hardman, Tim

2016-02-01

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Propofol-Based Palliative Sedation to Treat Antipsychotic-Resistant Agitated Delirium.

PubMed

Covarrubias-Gómez, Alfredo; López Collada-Estrada, Maria

Delirium is a common problem in terminally ill patients that is associated with significant distress and, hence, considered a palliative care emergency. The three subtypes of delirium are hyperactive, hypoactive, and mixed, depending on the level of psychomotor activity and arousal disturbance. When agitated delirium becomes refractory in the setting of imminent dying, the agitation may be so severe that palliative sedation (PS) is required. Palliative sedation involves the administration of sedative medications with the purpose of reducing level of consciousness for patients with refractory suffering in the setting of a terminal illness. Propofol is a sedative that has a short duration of action and a very rapid onset. These characteristics make it relatively easy to titrate. Reported doses range from 50 to 70 mg per hour. The authors present a case of antipsychotic-resistant agitated delirium treated with a propofol intravenous infusion.

XEN glaucoma treatment system in the management of refractory glaucomas: a short review on trial data and potential role in clinical practice.

PubMed

De Gregorio, A; Pedrotti, E; Stevan, G; Bertoncello, A; Morselli, S

2018-01-01

The recent development of new devices that are significantly less invasive, collectively termed minimally invasive glaucoma surgery, offers new perspective of intraocular pressure reduction with less risk, short operating times, and rapid recovery. The aim of this work is to provide a panoramic review of the currently published clinical data to assess the potential role of XEN gel stent (Allergan PLC, Irvine, CA, USA) in the management of glaucoma, which is the only filtering minimally invasive glaucoma surgery device that allows the subconjunctival filtration. The ab interno placement of the XEN gel stent offers an alternative for lowering intraocular pressure in refractory glaucoma as a final step, and in patients intolerant to medical therapy as an early surgical approach with minimum conjunctival tissue disruption, restricted flow to avoid hypotony, and long-term safety.

Renal Denervation: Intractable Hypertension and Beyond

PubMed Central

Ariyanon, Wassawon; Mao, Huijuan; Adýbelli, Zelal; Romano, Silvia; Rodighiero, Mariapia; Reimers, Bernhard; La Vecchia, Luigi; Ronco, Claudio

2014-01-01

Background Hypertension continues to be a major burden of public health concern despite the recent advances and proven benefit of pharmacological therapy. A certain subset of patients has hypertension resistant to maximal medical therapy and appropriate lifestyle measures. A novel catheter-based technique for renal denervation (RDN) as a new therapeutic avenue has great promise for the treatment of refractory hypertension. Summary This review included the physiology of the renal sympathetic nervous system and the renal nerve anatomy. Furthermore, the RDN procedure, technology systems, and RDN clinical trials as well as findings besides antihypertensive effects were discussed. Findings on safety and efficacy seem to suggest that renal sympathetic denervation could be of therapeutic benefit in refractory hypertensive patients. Despite the fast pace of development in RDN therapies, only initial and very limited clinical data are available. Large gaps in knowledge concerning the long-term effects and consequences of RDN still exist, and solid, randomized data are warranted. PMID:24847331

Occipital neuralgia secondary to unilateral atlantoaxial osteoarthritis: Case report and review of the literature.

PubMed

Guha, Daipayan; Mohanty, Chandan; Tator, Charles H; Shamji, Mohammed F

2015-01-01

Atlantoaxial osteoarthritis (AAOA), either in isolation or in the context of generalized peripheral or spinal arthritis, presents most commonly with neck pain and limitation of cervical rotational range of motion. Occipital neuralgia (ON) is only rarely attributed to AAOA, as fewer than 30 cases are described in the literature. A 64-year-old female presented with progressive incapacitating cervicalgia and occipital headaches, refractory to medications, and local anesthetic blocks. Computed tomography and magnetic resonance imaging studies documented advanced unilateral atlantoaxial arthrosis with osteophytic compression that dorsally displaced the associated C2 nerve root. Surgical decompression and atlantoaxial fusion achieved rapid and complete relief of neuralgia. Ultimately, postoperative spinal imaging revealed osseous union. Atlantoaxial arthrosis must be considered in the differential diagnosis of ON. Surgical treatment is effective for managing refractory cases. Intraoperative neuronavigation is also a useful adjunct to guide instrumentation and the intraoperative extent of bony decompression.

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

PubMed Central

Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

2018-01-01

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

Late glaucoma after interstitial keratitis.

PubMed

Grant, W M

1975-01-01

In a systematic study of 45 patients who had syphilitic interstitial keratitis early in life and, many years later, were discovered to have glaucoma, there was evidence of two different but equally common mechanisms. In one group of patients, a deep-chamber type of glaucoma was superimposed on old inflammatory changes, was characteristically refractory to medical treatment, but did well with filtering surgery. The other group of patients had reversible angle-closure glaucoma associated with anatomically small anterior segments, and typically responded well to iridectomy. The late, refractory, deep-chamber type of glaucoma may involve endothelialization and formation of glass membrane in the angle, as seen in one excised eye. Occurrence of the shallow-chamber, reversible angle-closure type of glaucoma after interstitial keratitis may be coincidental, since no other evidence supports the idea that small anterior segments might be particularly prevalent among patients who have had congenital syphilis or interstitial keratitis.

XEN glaucoma treatment system in the management of refractory glaucomas: a short review on trial data and potential role in clinical practice

PubMed Central

De Gregorio, A; Pedrotti, E; Stevan, G; Bertoncello, A; Morselli, S

2018-01-01

The recent development of new devices that are significantly less invasive, collectively termed minimally invasive glaucoma surgery, offers new perspective of intraocular pressure reduction with less risk, short operating times, and rapid recovery. The aim of this work is to provide a panoramic review of the currently published clinical data to assess the potential role of XEN gel stent (Allergan PLC, Irvine, CA, USA) in the management of glaucoma, which is the only filtering minimally invasive glaucoma surgery device that allows the subconjunctival filtration. The ab interno placement of the XEN gel stent offers an alternative for lowering intraocular pressure in refractory glaucoma as a final step, and in patients intolerant to medical therapy as an early surgical approach with minimum conjunctival tissue disruption, restricted flow to avoid hypotony, and long-term safety. PMID:29750009

A Phase 1-2 Multi-Center Study Evaluating Axicabtagene Ciloleucel in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

ClinicalTrials.gov

2018-06-18

Refractory Diffuse Large B Cell Lymphoma; Refractory Primary Mediastinal B Cell Lymphoma; Refractory Transformed Follicular Lymphoma; Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma; Relapsed/Refractory Large B Cell Lymphoma Including DLBCL, PMBCL, TFL and HGBCL After Two Systemic Lines of Therapy" in Phase 2 Expanded Cohorts

Stem cell transplant in inflammatory bowel disease: a promising modality of treatment for a complicated disease course.

PubMed

Salem, George A; Selby, George B

2017-01-01

Inflammatory bowel disease (IBD) is a complex, relapsing and remitting, disease characterized by an exaggerated immune response in a susceptible host. The symptoms and complications of the disease can be debilitating. Advances in medical treatment in the last decade changed the course of the disease in many patients. Despite the use of novel agents for controlling disease, a proportion of patients' disease courses continue to be either refractory, or become resistant, to available therapeutic options. Stem-cell therapy, with hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs), is a promising modality of treatment for severe refractory cases, mainly Crohn's disease (CD) patients. HSCs have the ability to migrate to damaged tissue, which provides them with further properties to differentiate to epithelial or immune-modulatory cells to restore normal mucosal tissue and integrity. MSCs therapy is a promising model for patients with perianal CD due to their immunosuppressive properties, ability to migrate to areas of injury, and demonstration of colonic healing, including fistulizing tracts. The results from ongoing clinical trials will provide a valuable understanding of the future of stem-cell therapy as a treatment option in refractory cases of IBD, a disease whose pathogenesis remains unknown, and is notoriously difficult to treat.

Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pereira, Keith, E-mail: keithjppereira@gmail.com; Carrion, Andres F., E-mail: andres.carrionmonsa@jhsmiami.org; Salsamendi, Jason, E-mail: JSalsamendi@med.miami.edu

Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3–7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between differentmore » specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a ‘bridge’ therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.« less

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

PubMed

Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F

2010-11-01

Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be relatively common, and not typically associated with hippocampal sclerosis, is an appropriate target for contemporary approaches to complex disorders such as genome-wide association studies for common genetic variants or deep sequencing for rare variants.

Risk factors for spatial memory impairment in patients with temporal lobe epilepsy.

PubMed

Amlerova, Jana; Laczo, Jan; Vlcek, Kamil; Javurkova, Alena; Andel, Ross; Marusic, Petr

2013-01-01

At present, the risk factors for world-centered (allocentric) navigation impairment in patients with temporal lobe epilepsy (TLE) are not known. There is some evidence on the importance of the right hippocampus but other clinical features have not been investigated yet. In this study, we used an experimental human equivalent to the Morris water maze to examine spatial navigation performance in patients with drug-refractory unilateral TLE. We included 47 left-hemisphere speech dominant patients (25 right sided; 22 left sided). The aim of our study was to identify clinical and demographic characteristics of TLE patients who performed poorly in allocentric spatial memory tests. Our results demonstrate that poor spatial navigation is significantly associated with younger age at epilepsy onset, longer disease duration, and lower intelligence level. Allocentric navigation in TLE patients was impaired irrespective of epilepsy lateralization. Good and poor navigators did not differ in their age, gender, or preoperative/postoperative status. This study provides evidence on risk factors that increase the likelihood of allocentric navigation impairment in TLE patients. The results indicate that not only temporal lobe dysfunction itself but also low general cognitive abilities may contribute to the navigation impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

The CardiAMP Heart Failure trial: A randomized controlled pivotal trial of high-dose autologous bone marrow mononuclear cells using the CardiAMP cell therapy system in patients with post-myocardial infarction heart failure: Trial rationale and study design.

PubMed

Raval, Amish N; Cook, Thomas D; Duckers, Henricus J; Johnston, Peter V; Traverse, Jay H; Abraham, William T; Altman, Peter A; Pepine, Carl J

2018-07-01

Heart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. CardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. This novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure. Copyright © 2018 Elsevier Inc. All rights reserved.

Using preoperative unsupervised cluster analysis of chronic rhinosinusitis to inform patient decision and endoscopic sinus surgery outcome.

PubMed

Adnane, Choaib; Adouly, Taoufik; Khallouk, Amine; Rouadi, Sami; Abada, Redallah; Roubal, Mohamed; Mahtar, Mohamed

2017-02-01

The purpose of this study is to use unsupervised cluster methodology to identify phenotype and mucosal eosinophilia endotype subgroups of patients with medical refractory chronic rhinosinusitis (CRS), and evaluate the difference in quality of life (QOL) outcomes after endoscopic sinus surgery (ESS) between these clusters for better surgical case selection. A prospective cohort study included 131 patients with medical refractory CRS who elected ESS. The Sino-Nasal Outcome Test (SNOT-22) was used to evaluate QOL before and 12 months after surgery. Unsupervised two-step clustering method was performed. One hundred and thirteen subjects were retained in this study: 46 patients with CRS without nasal polyps and 67 patients with nasal polyps. Nasal polyps, gender, mucosal eosinophilia profile, and prior sinus surgery were the most discriminating factors in the generated clusters. Three clusters were identified. A significant clinical improvement was observed in all clusters 12 months after surgery with a reduction of SNOT-22 scores. There was a significant difference in QOL outcomes between clusters; cluster 1 had the worst QOL improvement after FESS in comparison with the other clusters 2 and 3. All patients in cluster 1 presented CRSwNP with the highest mucosal eosinophilia endotype. Clustering method is able to classify CRS phenotypes and endotypes with different associated surgical outcomes.

Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment.

PubMed

Alguire, Catherine; Chbat, Jessica; Forest, Isabelle; Godbout, Ariane; Bourdeau, Isabelle

2018-01-01

Pheochromocytoma is a rare tumor of the adrenal gland. It often presents with the classic triad of headache, palpitations and generalized sweating. Although not described as a typical symptom of pheochromocytoma, anxiety is the fourth most common symptom reported by patients suffering of pheochromocytoma. We report the case of a 64 year old man who had severe anxiety and panic disorder as presenting symptoms of pheochromocytoma. After 13 years of psychiatric follow-up, the patient was diagnosed with malignant pheochromocytoma. After surgical resection of his pheochromocytoma and his hepatic metastases, the major panic attacks completely disappeared, the anxiety symptoms improved significantly and the psychiatric medications were stopped except for a very low maintenance dose of venlafaxine. We found in our cohort of 160 patients with pheochromocytoma 2 others cases of apparently benign tumors with severe anxiety that resolved after pheochromocytoma resection. These cases highlight that pheochromocytoma should be included in the differential diagnosis of refractory anxiety disorder. Anxiety and panic disorder may be the main presenting symptoms of pheochromocytoma.The diagnosis of pheochromocytoma should be excluded in cases of long-term panic disorder refractory to medications since the anxiety may be secondary to a catecholamine-secreting tumor.Surgical treatment of pheochromocytoma leads to significant improvement of anxiety disorders.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

PubMed

Boes, Aaron D; Kelly, Michael S; Trapp, Nicholas T; Stern, Adam P; Press, Daniel Z; Pascual-Leone, Alvaro

2018-04-24

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Production and application of chemical fibers with special properties for manufacturing composite materials and goods of different usage

NASA Technical Reports Server (NTRS)

Levit, R.

1993-01-01

The development of modern technologies demands the creation of new nonmetallic, fibrous materials with specific properties. The fibers and materials developed by NII 'Chimvolokno', St. Petersburg, can be divided into two groups. The first group includes heat-resistant fibers, fire-resistant fibers, thermotropic fibers, fibers for medical application, and textile structures. The second group contains refractory fibers, chemoresistant and antifriction fibers, fibers on the basis of polyvinyl alcohol, microfiltering films, and paperlike and nonwoven materials. In cooperation with NPO 'Chimvolokno' MYTITSHI, we developed and started producing heat-resistant high-strength fibers on the base of polyhetarearilin and aromatic polyimides (SVM and terlon); heat-resistant fibers on the base of polyemede (aramid); fire-retardant fibers (togilen); chemoresistant and antifriction fibers on the basis of homo and copolymers of polytetrafluoroethylene (polyfen and ftorin); and water soluble, acetylated, and high-modulus fibers from polyvinyl alcohol (vylen). Separate reports will deal with textile structures and thermotropic fibers, as well as with medical fibers. One of the groups of refractory fibers carbon fibers (CF) and the corresponding paperlike nonwoven materials are discussed in detail. Also, composite materials (CM) and their base, which is the subject of the author's research since 1968, is discussed.

Seizure clusters: characteristics and treatment.

PubMed

Haut, Sheryl R

2015-04-01

Many patients with epilepsy experience 'clusters' or flurries of seizures, also termed acute repetitive seizures (ARS). Seizure clustering has a significant impact on health and quality of life. This review summarizes recent advances in the definition and neurophysiologic understanding of clustering, the epidemiology and risk factors for clustering and both inpatient and outpatient clinical implications. New treatments for seizure clustering/ARS are perhaps the area of greatest recent progress. Efforts have focused on creating a uniform definition of a seizure cluster. In neurophysiologic studies of refractory epilepsy, seizures within a cluster appear to be self-triggering. Clinical progress has been achieved towards a more precise prevalence of clustering, and consensus guidelines for epilepsy monitoring unit safety. The greatest recent advances are in the study of nonintravenous route of benzodiazepines as rescue medications for seizure clusters/ARS. Rectal benzodiazepines have been very effective but barriers to use exist. New data on buccal, intramuscular and intranasal preparations are anticipated to lead to a greater number of approved treatments. Progesterone may be effective for women who experience catamenial clusters. Seizure clustering is common, particularly in the setting of medically refractory epilepsy. Clustering worsens health and quality of life, and the field requires greater focus on clarifying of definition and clinical implications. Progress towards the development of nonintravenous routes of benzodiazepines has the potential to improve care in this area.

Examination of nanosecond laser melting thresholds in refractory metals by shear wave acoustics

NASA Astrophysics Data System (ADS)

Abdullaev, A.; Muminov, B.; Rakhymzhanov, A.; Mynbayev, N.; Utegulov, Z. N.

2017-07-01

Nanosecond laser pulse-induced melting thresholds in refractory (Nb, Mo, Ta and W) metals are measured using detected laser-generated acoustic shear waves. Obtained melting threshold values were found to be scaled with corresponding melting point temperatures of investigated materials displaying dissimilar shearing behavior. The experiments were conducted with motorized control of the incident laser pulse energies with small and uniform energy increments to reach high measurement accuracy and real-time monitoring of the epicentral acoustic waveforms from the opposite side of irradiated sample plates. Measured results were found to be in good agreement with numerical finite element model solving coupled elastodynamic and thermal conduction governing equations on structured quadrilateral mesh. Solid-melt phase transition was handled by means of apparent heat capacity method. The onset of melting was attributed to vanished shear modulus and rapid radial molten pool propagation within laser-heated metal leading to preferential generation of transverse acoustic waves from sources surrounding the molten mass resulting in the delay of shear wave transit times. Developed laser-based technique aims for applications involving remote examination of rapid melting processes of materials present in harsh environment (e.g. spent nuclear fuels) with high spatio-temporal resolution.

Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

ClinicalTrials.gov

2018-04-27

Blastic Plasmacytoid Dendritic Cell Neoplasm; Hepatosplenic T-Cell Lymphoma; HTLV-1 Infection; NK-Cell Lymphoma, Unclassifiable; Primary Systemic Anaplastic Large Cell Lymphoma, ALK-Negative; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Mycosis Fungoides; Refractory Adult T-Cell Leukemia/Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Mycosis Fungoides; Refractory Nasal Type Extranodal NK/T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

ClinicalTrials.gov

2018-03-12

Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Plasma Cell Myeloma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Plasma Cell Myeloma; Refractory T-Cell Non-Hodgkin Lymphoma

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

ClinicalTrials.gov

2018-05-02

High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; MYC Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Localization of dense intracranial electrode arrays using magnetic resonance imaging

PubMed Central

Doyle, Werner K.; Halgren, Eric; Carlson, Chad; Belcher, Thomas L.; Cash, Sydney S.; Devinsky, Orrin; Thesen, Thomas

2013-01-01

Intracranial electrode arrays are routinely used in the pre-surgical evaluation of patients with medically refractory epilepsy, and recordings from these electrodes have been increasingly employed in human cognitive neurophysiology due to their high spatial and temporal resolution. For both researchers and clinicians, it is critical to localize electrode positions relative to the subject-specific neuroanatomy. In many centers, a post-implantation MRI is utilized for electrode detection because of its higher sensitivity for surgical complications and the absence of radiation. However, magnetic susceptibility artifacts surrounding each electrode prohibit unambiguous detection of individual electrodes, especially those that are embedded within dense grid arrays. Here, we present an efficient method to accurately localize intracranial electrode arrays based on pre- and post-implantation MR images that incorporates array geometry and the individual's cortical surface. Electrodes are directly visualized relative to the underlying gyral anatomy of the reconstructed cortical surface of individual patients. Validation of this approach shows high spatial accuracy of the localized electrode positions (mean of 0.96 mm±0.81 mm for 271 electrodes across 8 patients). Minimal user input, short processing time, and utilization of radiation-free imaging are strong incentives to incorporate quantitatively accurate localization of intracranial electrode arrays with MRI for research and clinical purposes. Co-registration to a standard brain atlas further allows inter-subject comparisons and relation of intracranial EEG findings to the larger body of neuroimaging literature. PMID:22759995

Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8-Year-Old Child.

PubMed

Bradley, Lucas; Bahgat, Diaa; Sharp, Gregory; Willis, Erin; Ocal, Eylem; Albert, Gregory; Serletis, Demitre

2015-10-01

We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure-free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies.

Carbamazepine toxicity during combination therapy with levetiracetam: a pharmacodynamic interaction.

PubMed

Sisodiya, Sanjay M; Sander, Josemir W A S; Patsalos, Philip N

2002-02-01

Levetiracetam is a novel antiepileptic drug with an unknown mechanism of action. To-date levetiracetam is not known to be associated with any clinically significant pharmacokinetic interaction. Similarly, levetiracetam has not been associated with any pharmacodynamic interactions. We present four patients with severe refractory epilepsy in whom introduction of levetiracetam led to disabling symptoms compatible with carbamazepine toxicity requiring either carbamazepine dose reduction or levetiracetam withdrawal. As carbamazepine and carbamazepine-epoxide blood levels were not altered during levetiracetam co-medication, a pharmacodynamic interaction is suggested. Therefore, during levetiracetam co-medication with carbamazepine, patients should be monitored closely for symptoms of carbamazepine toxicity.

Massive Atenolol, Lisinopril, and Chlorthalidone Overdose Treated with Endoscopic Decontamination, Hemodialysis, Impella Percutaneous Left Ventricular Assist Device, and ECMO.

PubMed

Heise, C William; Beutler, David; Bosak, Adam; Orme, Geoffrey; Loli, Akil; Graeme, Kimberlie

2015-03-01

Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome. Aggressive medical intervention did not provide sufficient hemodynamic stability in this patient with refractory cardiogenic and distributive shock. Impella® percutaneous left ventricular assist device and extracorporeal membrane oxygenation provided support while the effects of the overdose subsided. We present concentrations demonstrating removal of atenolol with continuous venovenous hemodiafiltration. This is the first report of esophagogastroduo denoscopy decontamination of this overdose with a large pill fragment burden.

Surgical Management of Neurogenic Lower Urinary Tract Dysfunction.

PubMed

Gor, Ronak A; Elliott, Sean P

2017-08-01

Surgery for patients with neurogenic urinary tract dysfunction (nLUTD) is indicated when medical therapy fails, to correct conditions affecting patient safety, or when surgery can enhance the quality of life better than nonoperative management. Examples include failure of maximal medical therapy, inability to perform or aversion to clean intermittent catheterization, refractory incontinence, and complications from chronic, indwelling catheters. Adults with nLUTD have competing risk factors, including previous operations, obesity, poor nutritional status, complex living arrangements, impaired dexterity/paralysis, and impaired executive and cognitive function. Complications are common in this subgroup of patients requiring enduring commitments from surgeons, patients, and their caretakers. Copyright © 2017 Elsevier Inc. All rights reserved.

Surgical outcome in patients with epilepsy and dual pathology.

PubMed

Li, L M; Cendes, F; Andermann, F; Watson, C; Fish, D R; Cook, M J; Dubeau, F; Duncan, J S; Shorvon, S D; Berkovic, S F; Free, S; Olivier, A; Harkness, W; Arnold, D L

1999-05-01

High-resolution MRI can detect dual pathology (an extrahippocampal lesion plus hippocampal atrophy) in about 5-20% of patients with refractory partial epilepsy referred for surgical evaluation. We report the results of 41 surgical interventions in 38 adults (mean age 31 years, range 14-63 years) with dual pathology. Three patients had two operations. The mean postoperative follow-up was 37 months (range 12-180 months). The extrahippocampal lesions were cortical dysgenesis in 15, tumour in 10, contusion/infarct in eight and vascular malformation in five patients. The surgical approach aimed to remove what was considered to be the most epileptogenic lesion, and the 41 operations were classified into lesionectomy (removal of an extrahippocampal lesion); mesial temporal resection (removal of an atrophic hippocampus); and lesionectomy plus mesial temporal resection (removal of both the lesion and the atrophic hippocampus). Lesionectomy plus mesial temporal resection resulted in complete freedom from seizures in 11/15 (73%) patients, while only 2/10 (20%) patients who had mesial temporal resection alone and 2/16 (12.5%) who had a lesionectomy alone were seizure-free (P < 0.001). When classes I and II were considered together results improved to 86, 30 and 31%, respectively. Our findings indicate that in patients with dual pathology removal of both the lesion and the atrophic hippocampus is the best surgical approach and should be considered whenever possible.

Percutaneous and Endoscopic Adhesiolysis in Managing Low Back and Lower Extremity Pain: A Systematic Review and Meta-analysis.

PubMed

Helm, Standiford; Racz, Gabor B; Gerdesmeyer, Ludger; Justiz, Rafael; Hayek, Salim M; Kaplan, Eugene D; El Terany, Mohamed Ahamed; Knezevic, Nebojsa Nick

2016-02-01

Chronic refractory low back and lower extremity pain is frustrating to treat. Percutaneous adhesiolysis and spinal endoscopy are techniques which can treat chronic refractory low back and lower extremity pain.Percutaneous adhesiolysis is performed by placing the catheter into the tissue plane at the ventrolateral aspect of the foramen so that medications can be injected. Adhesiolysis is used both for pain caused by scarring which is not resistant to catheter placement and other sources of pain, including inflammation in the absence of scarring.Mechanical lysis of scars with a catheter may or may not be necessary for percutaneous adhesiolysis to be effective. Spinal endoscopy allows direct visualization of the epidural space and has the possibility to use laser energy to treat pathology. A systematic review of the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. To evaluate and update the effectiveness of percutaneous adhesiolysis and spinal endoscopic adhesiolysis to treat chronic refractory low back and lower extremity pain. The available literature on percutaneous adhesiolysis and spinal endoscopic adhesiolysis in treating persistent low back and leg pain was reviewed. The quality of each article used in this analysis was assessed. The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials to weak, based upon consensus, as developed by the U.S. Preventive Services Task Force (USPSTF) and modified by ASIPP. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015, and manual searches of the bibliographies of known primary and review articles. Pain relief of at least 50% and functional improvement of at least 40% were the primary outcome measures. Short-term efficacy was defined as improvement of 6 months or less; whereas, long-term efficacy was defined more than 6 months. For this systematic review, 45 studies were identified. Of these, for percutaneous adhesiolysis there were 7 randomized controlled trials and 3 observational studies which met the inclusion criteria. For spinal endoscopy, there was one randomized controlled trial and 3 observational studies. Based upon 7 randomized controlled trials showing efficacy, with no negative trials, there is Level I or strong evidence of the efficacy of percutaneous adhesiolysis in the treatment of chronic refractory low back and lower extremity pain. Based upon one high-quality randomized controlled trial, there is Level II to III evidence supporting the use of spinal endoscopy in treating chronic refractory low back and lower extremity pain. The evidence is Level I or strong that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain. Percutaneous adhesiolysis may be considered as a first-line treatment for chronic refractory low back and lower extremity pain. The evidence is Level II to III that spinal endoscopy is effective in the treatment of chronic refractory low back and lower extremity pain. Spinal pain, chronic low back pain, post lumbar surgery syndrome, epidural scarring, adhesiolysis, endoscopy, radicular pain.

A Method for Automatic Extracting Intracranial Region in MR Brain Image

NASA Astrophysics Data System (ADS)

Kurokawa, Keiji; Miura, Shin; Nishida, Makoto; Kageyama, Yoichi; Namura, Ikuro

It is well known that temporal lobe in MR brain image is in use for estimating the grade of Alzheimer-type dementia. It is difficult to use only region of temporal lobe for estimating the grade of Alzheimer-type dementia. From the standpoint for supporting the medical specialists, this paper proposes a data processing approach on the automatic extraction of the intracranial region from the MR brain image. The method is able to eliminate the cranium region with the laplacian histogram method and the brainstem with the feature points which are related to the observations given by a medical specialist. In order to examine the usefulness of the proposed approach, the percentage of the temporal lobe in the intracranial region was calculated. As a result, the percentage of temporal lobe in the intracranial region on the process of the grade was in agreement with the visual sense standards of temporal lobe atrophy given by the medical specialist. It became clear that intracranial region extracted by the proposed method was good for estimating the grade of Alzheimer-type dementia.

Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

ClinicalTrials.gov

2017-10-24

CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

[Efficacy of infliximab in the treatment of korean patients with crohns disease].

PubMed

Kim, Sai Hui; Yang, Suk; Kim, Kyung Jo; Kim, Eun Hee; Yoon, Soon Man; Ye, Byong Duk; Byeon, Jeong Sik; Myung, Seung Jae; Kim, Jin Ho

2009-08-01

Infliximab has been proven to be effective for refractory luminal and fistulizing Crohns disease (CD). We performed this study to demonstrate the efficacy of infliximab in Korean CD patients. Medical records of 40 CD patients who had been treated with infliximab were reviewed retrospectively. Among 40 patients, 11 (27.5%) patients were treated for refractory luminal disease, 14 (35%) for fistulizing disease, and 15 (37.5%) for both types. Clinical response rate was higher in 26 patients with refractory luminal disease (Complete response (CR), 73.1%; Partial response (PR), 23.1%) than in 29 patients with fistulizing disease (CR, 41.4%; PR, 31%) (p=0.024). The clinical response rate tended to be higher in 28 patients with external fistulas (CR, 46.4%; PR, 32.2%) than 4 patients with internal fistulas (PR, 25%; NR, 75%) (p=0.064). Among patients with external fistulas, the response rate of 8 patients with enterocutaneous fistulas (CR, 50%; PR, 12.5%) was not different from 20 patients with perianal fistulas (CR, 45%; PR, 40%). Among 20 patients with perianal fistulas, the response rate of 6 patients with perianal fistulas without a history of operation (CR, 83.3%; PR, 0%) was higher than 14 patients with perianal fistulas resistant to previous surgical treatment (CR, 28.6%; PR, 57.1%) (p=0.044). As for adverse reaction, 7 patients experienced mild infusion reaction, and 2 patients developed serious infection. Infliximab is more effective for refractory luminal disease than for fistulizing disease. In addition, clinical responses to infliximab are different according to subtypes of fistulas. These findings should be considered for the proper use of infliximab.

Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Crohn’s Disease: Current Status and Future Directions. A Review on Behalf of the EBMT Autoimmune Diseases Working Party and the Autologous Stem Cell Transplantation In Refractory CD—Low Intensity Therapy Evaluation Study Investigators

PubMed Central

Pockley, Alan Graham; Lindsay, James O.; Foulds, Gemma A.; Rutella, Sergio; Gribben, John G.; Alexander, Tobias; Snowden, John A.

2018-01-01

Patients with treatment refractory Crohn’s disease (CD) suffer debilitating symptoms, poor quality of life, and reduced work productivity. Surgery to resect inflamed and fibrotic intestine may mandate creation of a stoma and is often declined by patients. Such patients continue to be exposed to medical therapy that is ineffective, often expensive and still associated with a burden of adverse effects. Over the last two decades, autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a promising treatment option for patients with severe autoimmune diseases (ADs). Mechanistic studies have provided proof of concept that auto-HSCT can restore immunological tolerance in chronic autoimmunity via the eradication of pathological immune responses and a profound reconfiguration of the immune system. Herein, we review current experience of auto-HSCT for the treatment of CD as well as approaches that have been used to monitor immune reconstitution following auto-HSCT in patients with ADs, including CD. We also detail immune reconstitution studies that have been integrated into the randomized controlled Autologous Stem cell Transplantation In refractory CD—Low Intensity Therapy Evaluation trial, which is designed to test the hypothesis that auto-HSCT using reduced intensity mobilization and conditioning regimens will be a safe and effective means of inducing sustained control in refractory CD compared to standard of care. Immunological profiling will generate insight into the pathogenesis of the disease, restoration of responsiveness to anti-TNF therapy in patients with recurrence of endoscopic disease and immunological events that precede the onset of disease in patients that relapse after auto-HSCT. PMID:29670622

Diagnostic yield of capsule endoscopy in refractory celiac disease.

PubMed

Barret, Maximilien; Malamut, Georgia; Rahmi, Gabriel; Samaha, Elia; Edery, Joël; Verkarre, Virginie; Macintyre, Elizabeth; Lenain, Emilie; Chatellier, Gilles; Cerf-Bensussan, Nadine; Cellier, Christophe

2012-10-01

Capsule endoscopy (CE) allows for the assessment of the small bowel in numerous intestinal diseases, including celiac disease (CD). The main advantage of CE is the complete visualization of the intestinal mucosal surface. The objective of this study was to investigate whether CE can predict the severity of CD and detect complications. We retrospectively studied the medical files of 9 patients with symptomatic CD, 11 patients with refractory celiac disease type I (RCDI) and 18 patients with refractory celiac disease type II (RCDII), and 45 patients without CD who were investigated both CE and upper endoscopy or enteroscopy. The type of CD was diagnosed on the basis of a centralized histological review, flow cytometry analysis of intraepithelial lymphocytes, and the analysis of T-cell receptor rearrangement by multiplex polymerase chain reaction. A total of 47 CEs (10, 11, and 26 CEs in the symptomatic CD, RCDI, and RCDII groups, respectively) from the 38 celiac patients and 47 CEs from the 45 nonceliac patients were retrospectively reviewed. Villous atrophy, numerous, or distally located ulcers were more frequent in celiac patients than in controls. Among celiac patients, CE was of acceptable quality in 96% of cases and was complete in 62% of cases. The concordance of CE with histology for villous atrophy was better than that of optic endoscopy (κ coefficient =0.45 vs. 0.24, P<0.001). Extensive mucosal damage on CE was associated with low serum albumin (P=0.003) and the RCDII form (P=0.02). Three cases of overt lymphoma were detected by CE during the follow-up. CE findings have a satisfactory concordance with histology and nutritional status in patients with symptomatic or refractory CD. Moreover, CE may predict the type of RCD and allows for the early detection of overt lymphoma.

Treatment of transfusional iron overload in patients with myelodysplastic syndrome or severe anemia: data from multicenter clinical practices.

PubMed

Raptis, Anastasios; Duh, Mei Sheng; Wang, Si-Tien; Dial, Ellison; Fanourgiakis, Ilias; Fortner, Barry; Paley, Carole; Mody-Patel, Nikita; Corral, Mitra; Scott, Jeffrey

2010-01-01

Patients with myelodysplastic syndrome (MDS) or severe anemia requiring repeated red blood cell (RBC) transfusions risk developing transfusional iron overload, which can reduce survival. Iron chelation therapy (ICT) has been shown to improve survival and quality of life in patients; however, ICT utilization in clinical practices is not well understood. Medical records of patients diagnosed with MDS or severe anemia at least 6 months before data extraction, aged at least 21 years at diagnosis, and who received at least one RBC transfusion were reviewed. ICT eligibility was defined as at least 20 units of RBCs transfused or at least two serum ferritin levels exceeding 1000 microg/L. Study endpoint was ICT treatment rate among ICT-eligible patients with lower-risk MDS (International Prognostic Scoring System [low or intermediate-1]; World Health Organization [refractory anemia {RA}, refractory anemia with ringed sideroblasts {RARS}, refractory cytopenia with multilineage dysplasia {RCMD}, refractory cytopenia with multilineage dysplasia and ringed sideroblasts, or 5q]; French-American-British [RA/RARS]). Among 78 ICT-eligible patients with lower-risk MDS, 32 (41%) received ICT. At ICT initiation, treated patients received on average 13.3 transfusions (27.6 units) and mean first post-ICT initiation serum ferritin was twice the MDS Foundation recommendation at 1949 microg/L. Median overall survival for all ICT-eligible patients was significantly longer for those ICT-treated patients than untreated patients (8.7 years vs. 4.7 years, log-rank p = 0.02; multivariate hazard ratio 0.372, p = 0.03). This study finds only 41% of ICT-eligible patients with lower-risk MDS received ICT in clinical practice, and treatment was initiated later than recommended. Receipt of ICT was associated with significantly longer survival.

Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory Glaucoma in the Mainland Chinese Population

PubMed Central

Yang, Xuejiao; Deng, Shuifeng; Li, Zuohong; Li, Fei; Zhuo, Yehong

2015-01-01

Background To evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV) and the risk factors associated with AGV implantation failure in a population of Chinese patients with refractory glaucoma. Method In total, 79 eyes with refractory glaucoma from 79 patients treated in our institution from November 2007 to November 2010 were enrolled in this retrospective study. The demographic data, preoperative and postoperative intraocular pressures (IOPs), best corrected visual acuity (BCVA), number of anti-glaucoma medications used, completed and qualified surgery success rates and postoperative complications were recorded to evaluate the outcomes of AGV implantation. Factors that were associated with implant failure were determined using Cox proportional hazard regression model analysis and multiple linear regression analysis. Principle Findings The average follow-up time was 12.7±5.8 months (mean±SD). We observed a significant reduction in the mean IOP from 39.9±12.6 mm Hg before surgery to 19.3±9.6 mm Hg at the final follow-up. The complete success rate was 59.5%, and the qualified success rate was 83.5%. The number of previous surgeries was negatively correlated with qualified success rate (P<0.05, OR=0.736, 95% CI 0.547-0.99). Patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control IOP (P<0.01). The primary complication was determined to be a flat anterior chamber (AC). Conclusion AGV implantation was safe and effective for the management of refractory glaucoma. Patients with a greater number of previous surgeries were more likely to experience surgical failure, and patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control postoperative IOP. PMID:25996991

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

PubMed

Gibbons, Kathleen; DeMonbrun, Andrea; Beckman, Elizabeth J; Keefer, Patricia; Wagner, Deb; Stewart, Margaret; Saul, D'Anna; Hakel, Stephanie; Liu, My; Niedner, Matthew

2016-07-01

Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children. © 2016 Wiley Periodicals, Inc.

Spinal cord stimulation for patients with refractory angina and previous coronary surgery.

PubMed

Lapenna, Elisabetta; Rapati, Dino; Cardano, Paola; De Bonis, Michele; Lullo, Francesca; Zangrillo, Alberto; Alfieri, Ottavio

2006-11-01

Refractory angina pectoris is an exceptionally debilitating condition affecting patients who have typically failed multiple percutaneous and surgical revascularizations and optimal medical therapy and who are not amenable for further revascularization procedures. Spinal cord stimulation (SCS) has been adopted in this context at our institution and midterm mortality, anginal status, and quality of life have been evaluated. From 1998 to 2004, 51 patients with refractory class III-IV angina, who were not considered candidates for revascularization procedures, underwent SCS. All patients had already undergone previous surgical revascularization and a median of two percutaneous procedures. Transmyocardial laser revascularization had been previously performed in 8 cases (15.6%). Most of the patients (70.5%) had experienced a myocardial infarction. Mean ejection fraction was 0.42 +/- 0.121, Canadian Cardiovascular Society class 3.5 +/- 0.5, quality of life (Spitzer index) 4.5 +/- 1.2, and the median frequency of weekly angina episodes was 10. There were no SCS implantation-related complications. At follow-up (100% complete, mean 24 +/- 18 months), a significant improvement of anginal symptoms (>50% reduction of weekly anginal episodes) occurred in 45 patients (88.2%). In those patients (Responders), the quality of life improved significantly (6.8 +/- 1.5; p < 0.0001), CCS class decreased to 2 +/- 0.7 (p < 0.0001), and the median frequency of weekly angina episodes to 3 (p < 0.0001). At 3 years, Responders' survival was 91.8 +/- 4.6% and the freedom from cardiac events 72.6 +/- 8.42%. Spinal cord stimulation is a safe and effective procedure in truly no-option patients affected by refractory angina. A midterm sustained improvement of symptoms and quality of life have been documented with a satisfactory 3-year survival rate.

Immediate and long-term clinical outcome after spinal cord stimulation for refractory stable angina pectoris.

PubMed

Di Pede, Francesco; Lanza, Gaetano Antonio; Zuin, Guerrino; Alfieri, Ottavio; Rapati, Massimo; Romanò, Massimo; Circo, Antonio; Cardano, Paola; Bellocci, Fulvio; Santini, Massimo; Maseri, Attilio

2003-04-15

The treatment of patients with angina pectoris refractory to medical therapy and unsuitable for revascularization procedures has yet not been well standardized. Previous retrospective studies and small prospective studies have suggested beneficial effects of spinal cord stimulation (SCS) in these patients. We created a Prospective Italian Registry of SCS to evaluate the short- and long-term clinical outcome of patients who underwent SCS device implantation because of severe refractory angina pectoris. Overall, 104 patients were enrolled in the registry (70 men, aged 68 +/- 17 years), most of whom (83%) had severe coronary artery disease. Average follow-up was 13.2 +/- 8 months. Overall, 17 patients (16%) died, 8 (8%) due to cardiac death. Among clinical variables, only age was found to be significantly associated both with total mortality (p = 0.04) and cardiac mortality (p = 0.02) on Cox regression analysis. A significant improvement of anginal symptoms (> or =50% reduction of weekly anginal episodes, compared with baseline) occurred in 73% of patients, and Canadian Cardiovascular Society angina class improved by > or =1 class in 80% and by > or =2 classes in 42% of patients, with a relevant reduction in the rate of hospital admission and days spent in the hospital because of angina (p <0.0001 for both). No life-threatening or clinically serious complications were observed. The most frequent side effect consisted of superficial infections, either at the site of puncture of electrode insertion or of the abdominal pocket, which occurred in 6 patients. In conclusion, our prospective data point out that SCS can be performed safely and is associated with a sustained improvement of anginal symptoms in a relevant number of patients with refractory stable angina pectoris.

The role of gastroesophageal reflux in relation to symptom onset in patients with proton pump inhibitor-refractory nonerosive reflux disease accompanied by an underlying esophageal motor disorder.

PubMed

Izawa, Shinya; Funaki, Yasushi; Iida, Akihito; Tokudome, Kentaro; Tamura, Yasuhiro; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

2014-01-01

The symptom improvement rate is low with proton pump inhibitors (PPIs) in nonerosive reflux disease (NERD). The underlying pathogenic mechanism is complex. Esophageal motility disorders (EMDs) are thought to be a factor, but their prevalence, type, symptoms and the role played by gastroesophageal reflux (GER) in symptom onset have not been fully investigated. To investigate the role of GER in symptom onset in PPI-refractory NERD patients with EMDs. This study comprised 76 patients with PPI-refractory NERD. Manometry was performed during PPI treatment and patients were divided into an EMD group and normal motility (non-EMD) group. Then, multichannel intraluminal impedance-pH monitoring was performed and medical interviews were conducted. Nineteen patients (25%) had an EMD. Data were compared between 17 patients, excluding 2 with achalasia and 57 non-EMD patients. No significant differences were observed between groups in 24-hour intraesophageal pH <4 holding time (HT), mean number of GER episodes or mean number of proximal reflux episodes. The reflux-related symptom index (≥50%) showed a relationship between reflux and symptoms in 70.5% of EMD patients and 75% of non-EMD patients. In the EMD group, the score for FSSG (Frequency Scale for the Symptoms of GERD) question (Q)10 was significantly correlated with the number of GER episodes (r = 0.58, p = 0.02) and the number of proximal reflux episodes (r = 0.63, p = 0.02). In addition, the score for Q9 tended to be correlated with the number of GER episodes (r = 0.44, p = 0.06). Our results suggest that some PPI-refractory NERD patients have EMDs, and that GER plays a role in symptom onset.

Clinical Outcomes of FP-7/8 Ahmed Glaucoma Valves in the Management of Refractory Glaucoma in the Mainland Chinese Population.

PubMed

Zhu, Yingting; Wei, Yantao; Yang, Xuejiao; Deng, Shuifeng; Li, Zuohong; Li, Fei; Zhuo, Yehong

2015-01-01

To evaluate the efficacy and safety of the Ahmed glaucoma valve (AGV) and the risk factors associated with AGV implantation failure in a population of Chinese patients with refractory glaucoma. In total, 79 eyes with refractory glaucoma from 79 patients treated in our institution from November 2007 to November 2010 were enrolled in this retrospective study. The demographic data, preoperative and postoperative intraocular pressures (IOPs), best corrected visual acuity (BCVA), number of anti-glaucoma medications used, completed and qualified surgery success rates and postoperative complications were recorded to evaluate the outcomes of AGV implantation. Factors that were associated with implant failure were determined using Cox proportional hazard regression model analysis and multiple linear regression analysis. The average follow-up time was 12.7±5.8 months (mean±SD). We observed a significant reduction in the mean IOP from 39.9±12.6 mm Hg before surgery to 19.3±9.6 mm Hg at the final follow-up. The complete success rate was 59.5%, and the qualified success rate was 83.5%. The number of previous surgeries was negatively correlated with qualified success rate (P<0.05, OR=0.736, 95% CI 0.547-0.99). Patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control IOP (P<0.01). The primary complication was determined to be a flat anterior chamber (AC). AGV implantation was safe and effective for the management of refractory glaucoma. Patients with a greater number of previous surgeries were more likely to experience surgical failure, and patients with previous trabeculectomy were more likely to use multiple anti-glaucoma drugs to control postoperative IOP.

Clinical assessment of diode laser-assisted endoscopic intrasphenoidal vidian neurectomy in the treatment of refractory rhinitis.

PubMed

Lai, Wen-Sen; Cheng, Sheng-Yao; Lin, Yuan-Yung; Yang, Pei-Lin; Lin, Hung-Che; Cheng, Li-Hsiang; Yang, Jinn-Moon; Lee, Jih-Chin

2017-12-01

For chronic rhinitis that is refractory to medical therapy, surgical intervention such as endoscopic vidian neurectomy (VN) can be used to control the intractable symptoms. Lasers can contribute to minimizing the invasiveness of ENT surgery. The aim of this retrospective study is to compare in patients who underwent diode laser-assisted versus traditional VN in terms of operative time, surgical field, quality of life, and postoperative complications. All patients had refractory rhinitis with a poor treatment response to a 6-month trial of corticosteroid nasal sprays and underwent endoscopic VN between November 2006 and September 2015. They were non-randomly allocated into either a cold instrument group or a diode laser-assisted group. Vidian nerve was excised with a 940-nm continuous wave diode laser through a 600-μm silica optical fiber, utilizing a contact mode with the power set at 5 W. A visual analog scale (VAS) was used to grade the severity of the rhinitis symptoms for quality of life assessment before the surgery and 6 months after. Of the 118 patients enrolled in the study, 75 patients underwent cold instrument VN and 43 patients underwent diode laser-assisted VN. Patients in the laser-assisted group had a significantly lower surgical field score and a lower postoperative bleeding rate than those in the cold instrument group. Changes in the VAS were significant in preoperative and postoperative nasal symptoms in each group. The application of diode lasers for vidian nerve transection showed a better surgical field and a lower incidence of postoperative hemorrhage. Recent advancements in laser application and endoscopic technique has made VN safer and more effective. We recommend this surgical approach as a reliable and effective treatment for patients with refractory rhinitis.

Parenting stress in parents of children with refractory epilepsy before and after vagus nerve stimulation implantation.

PubMed

Li, Sung-Tse; Chiu, Nan-Chang; Kuo, Yung-Ting; Shen, Ein-Yiao; Tsai, Pei-Chieh; Ho, Che-Sheng; Wu, Wen-Hsiang; Chen, Juei-Chao

2017-12-01

The purpose of this study was to evaluate parenting stress in parents of children with refractory epilepsy before and after their children received vagus nerve stimulation (VNS) implantation. Parents of children with refractory epilepsy completed the Parenting Stress Index (PSI) under a psychologist's assessment before and at least 12 months after their children received VNS implantation. The PSI questionnaire measures parenting stress in two domains; a parent domain with seven subscales, and a child domain with six. Age, gender, epilepsy comorbidity, VNS implantation date, seizure frequency, and anticonvulsant history before and after VNS implantation were obtained from reviews of medical charts. In total, 30 parents completed the first and follow-up PSI questionnaires. Seventeen of their children (56.7%) were boys. The children aged from 1 to 12 years (7.43 ± 3.59 years, mean ± SD). After VNS implantation, the mean total parenting stress scores decreased from 282.1 ± 38.0 to 272.4 ± 42.9. A significant decrease was found on the spouse subscale of the parent domain. For the parents of boys, the mean total parenting stress scores decreased significantly. The mean total parenting stress scores also decreased significantly for parents of epileptic children without autism and who did not taper off the number of different anticonvulsants used after VNS. VNS is an advisable choice to treat refractory epilepsy. Our study showed that 12 months or more after VNS implantation, seizure frequency and parenting stress typically decreased. However, in some special cases the parenting stress may increase, and external help may be required to support these patients and their parents. Copyright © 2017. Published by Elsevier B.V.

Genetic variation in arthropod vectors of disease-causing organisms: obstacles and opportunities.

PubMed Central

Gooding, R H

1996-01-01

An overview of the genetic variation in arthropods that transmit pathogens to vertebrates is presented, emphasizing the genetics of vector-pathogen relationships and the biochemical genetics of vectors. Vector-pathogen interactions are reviewed briefly as a prelude to a discussion of the genetics of susceptibility and refractoriness in vectors. Susceptibility to pathogens is controlled by maternally inherited factors, sex-linked dominant alleles, and dominant and recessive autosomal genes. There is widespread interpopulation (including intercolony) and temporal variation in susceptibility to pathogens. The amount of biochemical genetic variation in vectors is similar to that found in other invertebrates. However, the amount varies widely among species, among populations within species, and temporally within populations. Biochemical genetic studies show that there is considerable genetic structuring of many vectors at the local, regional, and global levels. It is argued that genetic variation in vectors is critical in understanding vector-pathogen interactions and that genetic variation in vectors creates both obstacles to and opportunities for application of genetic techniques to the control of vectors. PMID:8809462

Memory retrieval and the passage of time: from reconsolidation and strengthening to extinction

PubMed Central

Inda, Maria Carmen; Muravieva, Elizaveta V.; Alberini, Cristina M.

2011-01-01

An established memory can be made transiently labile if retrieved or reactivated. Over time, it becomes again resistant to disruption and this process that renders the memory stable is termed reconsolidation. The reasons why a memory becomes labile after retrieval and reconsolidates still remains debated. Here, using inhibitory avoidance (IA) learning in rats, we provide evidence that retrievals of a young memory, which are accompanied by its reconsolidation, result in memory strengthening and contribute to its overall consolidation. This function associated to reconsolidation is temporally limited. With the passage of time, the stored memory undergoes important changes, as revealed by the behavioral outcomes of its retrieval. Over time, without explicit retrievals, memory first strengthens and becomes refractory to both retrieval-dependent interference and strengthening. At later times, the same retrievals that lead to reconsolidation of a young memory extinguish an older memory. We conclude that the storage of information is very dynamic and that its temporal evolution regulates behavioral outcomes. These results are important for potential clinical applications. PMID:21289172

[The role of neurologists in deep brain stimulation for Parkinson disease: a neurosurgical perspective].

PubMed

Umemura, Atsushi

2012-01-01

Deep brain stimulation (DBS) has been accepted as an effective treatment for medically refractory Parkinson disease (PD). Appropriate patient selection, safe and precise surgery, and proper postoperative adjustment of stimulation and medication, are essential for the success of DBS. Patient selection is the most important role for the neurologist in DBS treatment. Neurologists treating PD should understand the correct indications and contraindications for DBS, and introduce it in a timely manner to patients who can be expected to benefit substantially from it. For long term treatment of PD, ideally the neurologist in charge of the patient should adjust both the stimulation parameters and medication. Neurologists engaged in this treatment should also have a comprehensive understanding of the probable complications and how to avoid them.

Microvascular decompression or neuromodulation in patients with SUNCT and trigeminal neurovascular conflict?

PubMed

Hassan, Samih; Lagrata, Susie; Levy, Andrew; Matharu, Manjit; Zrinzo, Ludvic

2018-02-01

Objectives To assess the effectiveness of neuromodulation and trigeminal microvascular decompression (MVD) in patients with medically-intractable short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Methods Two patients with medically refractory SUNCT underwent MVD following beneficial but incomplete response to neuromodulation (occipital nerve stimulation and deep brain stimulation). MRI confirmed neurovascular conflict with the ipsilateral trigeminal nerve in both patients. Results Although neuromodulation provided significant benefit, it did not deliver complete relief from pain and management required numerous postoperative visits with adjustment of medication and stimulation parameters. Conversely, MVD was successful in eliminating symptoms of SUNCT in both patients with no need for further medical treatment or neuromodulation. Conclusion Neuromodulation requires expensive hardware and lifelong follow-up and maintenance. These case reports highlight that microvascular decompression may be preferable to neuromodulation in the subset of SUNCT patients with ipsilateral neurovascular conflict.

Temporal Lobe Epilepsy in Children

PubMed Central

Nickels, Katherine C.; Wong-Kisiel, Lily C.; Moseley, Brian D.; Wirrell, Elaine C.

2012-01-01

The temporal lobe is a common focus for epilepsy. Temporal lobe epilepsy in infants and children differs from the relatively homogeneous syndrome seen in adults in several important clinical and pathological ways. Seizure semiology varies by age, and the ictal EEG pattern may be less clear cut than what is seen in adults. Additionally, the occurrence of intractable seizures in the developing brain may impact neurocognitive function remote from the temporal area. While many children will respond favorably to medical therapy, those with focal imaging abnormalities including cortical dysplasia, hippocampal sclerosis, or low-grade tumors are likely to be intractable. Expedient workup and surgical intervention in these medically intractable cases are needed to maximize long-term developmental outcome. PMID:22957247

Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-20

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Hodgkin Lymphoma; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; EZH2 Gain of Function; EZH2 Gene Mutation; Histiocytosis; Loss of BRG1 Protein Expression; Loss of INI 1 Protein Expression; Low Grade Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Hodgkin Lymphoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Hodgkin Lymphoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Soft Tissue Sarcoma; Rhabdoid Tumor; SMARCA4 Gene Inactivation; SMARCB1 Gene Inactivation; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Clinical characteristics, surgical and neuropsychological outcomes in drug resistant tumoral temporal lobe epilepsy.

PubMed

Ravat, Sangeeta; Iyer, Vivek; Muzumdar, Dattatraya; Shah, Urvashi; Pradhan, Pranjali; Jain, Neeraj; Godge, Yogesh

2016-12-01

Glioneuronal tumors are found in nearly one third patients who undergo surgery for pharmacoresistant epilepsy with temporal lobe being the most common location. Few studies, however have concentrated on the neurological and neuropsychological outcomes after surgery, hitherto none from India. We studied 34 patients with temporal lobe tumors and drug resistant epilepsy. These patients underwent anterior temporal lobectomy or lesionectomy based on the involvement of the hippocampus and mesial temporal structures. The clinical history, EEG, neuropsychology profile and MRI were compared. Seizure outcome was categorized using Engel's classification. At a mean follow up of 62 months, 85.29% of the patients were seizure free (Engel's Class I). All 8 patients with intraoperative electrocorticography (ECoG) guided resection were seizure free. Presence of a residual lesion was significantly associated with persistence of seizures post surgery (p = 0.002). Group analysis revealed no significant shifts in IQ and memory scores postoperatively. There was a significant improvement in the quality of life scores (total and across all subdomains) in all patients (p < 0.001). Postoperative EEG abnormalities predicted unfavorable ​seizure outcome. Surgery for temporal lobe tumors and refractory epilepsy offers complete seizure freedom in majority. Complete surgical excision of the epileptogenic zone is of paramount importance in achieving seizure freedom. Intraoperative electrocorticography (EcoG) is a useful adjunct to ensure complete removal of epileptogenic zone, thus achieving optimal seizure freedom. There is a significant improvement in the quality of life scores (p < 0.001) with no negative impact of surgery on memory and intelligence. Even the patients who are not seizure free can achieve worthwhile improvement post surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant

ClinicalTrials.gov

2017-10-03

Blastoid Variant Mantle Cell Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma

Development of refractories and related products for steel melting, finishing, and casting

NASA Astrophysics Data System (ADS)

Smirnov, A. N.

2013-06-01

The transformation of the consumption of refractories for the production, out-of-furnace treatment, and casting of steel is considered. The main trends in developing the refractory market are shown to be a significant decrease in the specific consumption of refractories per 1 t liquid steel and the predominant application of refractories based on magnesia raw materials and fused corundum for the working layers of melting units, ladles, and tundishes. The main trend in decreasing the specific costs of refractories is the development of refractories based on alternative sources of raw materials, which are cheaper and more available for refractory manufacturers.

Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2017-06-30

Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

Unexpected marked seizure improvement in paediatric epilepsy surgery candidates.

PubMed

Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

2017-02-01

Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later. Unexpected seizure control may occur during epilepsy surgery evaluation. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Cecal volvulus as a complication of gastric banding.

PubMed

Fakhro, Abdulla; O'Riordan, James M; Lawler, Leo P; O'Connell, P Ronan

2009-12-01

Surgery is an increasingly important management option for patients with obesity. Laparoscopic adjustable gastric banding is a procedure employed to treat morbid obesity refractory to medical therapy. It works by reducing the capacity of the stomach and promoting early satiety. We report the unusual case of a 33-year-old female who presented acutely 2 years following laparoscopic adjustable gastric banding with cecal volvulus and closed loop obstruction caused by displacement of the connecting tube.

Ocular Features of Cerebro-Costo-Mandibular Syndrome.

PubMed

Hameed, Zoya; Taylor, Simon; Lindfield, Dan

2018-01-01

Cerebro-costo-mandibular syndrome (CCMS) is a rare hereditary disorder characterized by micrognathia, posterior rib gaps, and secondary developmental delay. Patients often require ventilation and feeding support throughout life. We describe the first reported ophthalmic findings of CCMS and propose that defects in choroidal permeability lead to chronic macular edema and refractory aqueous misdirection syndrome. Here we discuss the medical and surgical management concerns of recurrent angle closure and raised intraocular pressure in a CCMS patient.

Simulation of axonal excitability using a Spreadsheet template created in Microsoft Excel.

PubMed

Brown, A M

2000-08-01

The objective of this present study was to implement an established simulation protocol (A.M. Brown, A methodology for simulating biological systems using Microsoft Excel, Comp. Methods Prog. Biomed. 58 (1999) 181-90) to model axonal excitability. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet and does not require any programming skills or use of the macro language. Once the initial spreadsheet template has been set up the simulations described in this paper can be executed with a few simple keystrokes. The model axon contained voltage-gated ion channels that were modeled using Hodgkin Huxley style kinetics. The basic properties of axonal excitability modeled were: (1) threshold of action potential firing, demonstrating that not only are the stimulus amplitude and duration critical in the generation of an action potential, but also the resting membrane potential; (2) refractoriness, the phenomenon of reduced excitability immediately following an action potential. The difference between the absolute refractory period, when no amount of stimulus will elicit an action potential, and relative refractory period, when an action potential may be generated by applying increased stimulus, was demonstrated with regard to the underlying state of the Na(+) and K(+) channels; (3) temporal summation, a process by which two sub-threshold stimuli can unite to elicit an action potential was shown to be due to conductance changes outlasting the first stimulus and summing with the second stimulus-induced conductance changes to drive the membrane potential past threshold; (4) anode break excitation, where membrane hyperpolarization was shown to produce an action potential by removing Na(+) channel inactivation that is present at resting membrane potential. The simulations described in this paper provide insights into mechanisms of axonal excitation that can be carried out by following an easily understood protocol.

Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

PubMed Central

Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

2016-01-01

Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and may represent a treatable underlying disease etiology in a subset of genetically susceptible patients with RUC, CFS, and other immune disorders. PMID:27165859

Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

ClinicalTrials.gov

2018-02-12

Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2018-01-25

Grade 3a Follicular Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-03-02

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

Lenalidomide in Treating Young Patients With Relapsed or Refractory Solid Tumors or Myelodysplastic Syndromes

ClinicalTrials.gov

2014-06-10

Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

ClinicalTrials.gov

2018-04-11

CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Indolent Non-Hodgkin Lymphoma

Basal Ganglia, Dopamine and Temporal Processing: Performance on Three Timing Tasks on and off Medication in Parkinson's Disease

ERIC Educational Resources Information Center

Jones, Catherine R. G.; Malone, Tim J. L.; Dirnberger, Georg; Edwards, Mark; Jahanshahi, Marjan

2008-01-01

A pervasive hypothesis in the timing literature is that temporal processing in the milliseconds and seconds range engages the basal ganglia and is modulated by dopamine. This hypothesis was investigated by testing 12 patients with Parkinson's disease (PD), both "on" and "off" dopaminergic medication, and 20 healthy controls on three timing tasks.…

Tuberculous temporal brain abscess mimicking otogenic pyogenic abscess.

PubMed

Muzumdar, D; Balasubramaniam, S; Melkundi, S

2009-01-01

Tuberculous brain abscess is a rare manifestation of central nervous system tuberculosis. We report the case of a tuberculous temporal lobe abscess in a 14-year-old female child that mimicked an otogenic pyogenic brain abscess. The patient had no prior history of tuberculosis. She had chronic otitis media and presented with signs of raised intracranial tension. Radiological imaging was suggestive of an acute pyogenic left temporal lobe abscess. A left temporal craniotomy was performed and the abscess was completely excised. Histological examination was consistent with a chronic abscess, and bacterial cultures were negative. A left radical mastoidectomy was also carried out. However, she presented with repeated abscess formation at the same site over the next 8 weeks, which was refractory to surgical therapy and broad-spectrum antibiotic administration. Furthermore, the purulent exudate showed strong positivity in the PCR test for tubercular bacilli. After administration of antituberculous treatment, she showed gradual clinical and radiological improvement. At follow-up after 2 years, she is asymptomatic. CT imaging at 2 years showed total resolution of abscess. Tuberculous abscess in the temporal lobe following otogenic infection has not been reported in the pediatric population. Although rare, the possibility of tuberculous etiology should be borne in mind as a differential diagnosis of acute abscess of otogenic origin, especially in endemic areas where the incidence of chronic otitis media as well as tuberculosis is high. The pathogenesis and treatment of tuberculous brain abscess in children is reviewed in light of the current literature on the subject. Copyright 2009 S. Karger AG, Basel.

A unified approach to the study of temporal, correlational, and rate coding.

PubMed

Panzeri, S; Schultz, S R

2001-06-01

We demonstrate that the information contained in the spike occurrence times of a population of neurons can be broken up into a series of terms, each reflecting something about potential coding mechanisms. This is possible in the coding regime in which few spikes are emitted in the relevant time window. This approach allows us to study the additional information contributed by spike timing beyond that present in the spike counts and to examine the contributions to the whole information of different statistical properties of spike trains, such as firing rates and correlation functions. It thus forms the basis for a new quantitative procedure for analyzing simultaneous multiple neuron recordings and provides theoretical constraints on neural coding strategies. We find a transition between two coding regimes, depending on the size of the relevant observation timescale. For time windows shorter than the timescale of the stimulus-induced response fluctuations, there exists a spike count coding phase, in which the purely temporal information is of third order in time. For time windows much longer than the characteristic timescale, there can be additional timing information of first order, leading to a temporal coding phase in which timing information may affect the instantaneous information rate. In this new framework, we study the relative contributions of the dynamic firing rate and correlation variables to the full temporal information, the interaction of signal and noise correlations in temporal coding, synergy between spikes and between cells, and the effect of refractoriness. We illustrate the utility of the technique by analyzing a few cells from the rat barrel cortex.

Magnetic Resonance-Guided Focused Ultrasound Neurosurgery for Essential Tremor: A Health Technology Assessment

PubMed Central

Schaink, Alexis; Li, Chunmei; Gajic-Veljanoski, Olga; Wells, David; Higgins, Caroline

2018-01-01

Background The standard treatment option for medication-refractory essential tremor is invasive neurosurgery. A new, noninvasive alternative is magnetic resonance-guided focused ultrasound (MRgFUS) neurosurgery. We aimed to determine the effectiveness, safety, and cost-effectiveness of MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario. We also spoke with people with essential tremor to gain an understanding of their experiences and thoughts regarding treatment options, including MRgFUS neurosurgery. Methods We performed a systematic review of the clinical literature published up to April 11, 2017, that examined MRgFUS neurosurgery alone or compared with other interventions for the treatment of moderate to severe, medication-refractory essential tremor. We assessed the risk of bias of each study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic review of the economic literature and created Markov cohort models to assess the cost-effectiveness of MRgFUS neurosurgery compared with other treatment options, including no surgery. We also estimated the budget impact of publicly funding MRgFUS neurosurgery in Ontario for the next 5 years. To contextualize the potential value of MRgFUS neurosurgery as a treatment option for essential tremor, we spoke with people with essential tremor and their families. Results Nine studies met our inclusion criteria for the clinical evidence review. In noncomparative studies, MRgFUS neurosurgery was found to significantly improve tremor severity and quality of life and to significantly reduce functional disability (GRADE: very low). It was also found to be significantly more effective than a sham procedure (GRADE: high). We found no significant difference in improvements in tremor severity, functional disability, or quality of life between MRgFUS neurosurgery and deep brain stimulation (GRADE: very low). We found no significant difference in improvement in tremor severity compared with radiofrequency thalamotomy (GRADE: low). MRgFUS neurosurgery has a favourable safety profile. We estimated that MRgFUS neurosurgery has a mean cost of $23,507 and a mean quality-adjusted survival of 3.69 quality-adjusted life-years (QALYs). We also estimated that the mean costs and QALYs of radiofrequency thalamotomy and deep brain stimulation are $14,978 and 3.61 QALYs, and $57,535 and 3.94 QALYs, respectively. For people ineligible for invasive neurosurgery, we estimated the incremental cost-effectiveness ratio (ICER) of MRgFUS neurosurgery compared with no surgery as $43,075 per QALY gained. In people eligible for invasive neurosurgery, the ICER of MRgFUS neurosurgery compared with radiofrequency thalamotomy is $109,795 per QALY gained; when deep brain stimulation is compared with MRgFUS neurosurgery, the ICER is $134,259 per QALY gained. Of note however, radiofrequency thalamotomy is performed very infrequently in Ontario. We also estimated that the budget impact of publicly funding MRgFUS neurosurgery in Ontario at the current case load (i.e., 48 cases/year) would be about $1 million per year for the next 5 years. People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences with the procedure. The tremor reduction they experienced improved their ability to perform activities of daily living and improved their quality of life. Conclusions MRgFUS neurosurgery is an effective and generally safe treatment option for moderate to severe, medication-refractory essential tremor. It provides a treatment option for people ineligible for invasive neurosurgery and offers a noninvasive option for all people considering neurosurgery. For people ineligible for invasive neurosurgery, MRgFUS neurosurgery is cost-effective compared with no surgery. In people eligible for invasive neurosurgery, MRgFUS neurosurgery may be one of several reasonable options. Publicly funding MRgFUS neurosurgery for the treatment of moderate to severe, medication-refractory essential tremor in Ontario at the current case load would have a net budget impact of about $1 million per year for the next 5 years. People with essential tremor who had undergone MRgFUS neurosurgery reported positive experiences. They liked that it was a noninvasive procedure and reported a substantial reduction in tremor that resulted in an improvement in their quality of life. PMID:29805721

Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection-Therapy: A Retrospective Study.

PubMed

Müller, Martin; Seufferlein, Thomas; Perkhofer, Lukas; Wagner, Martin; Kleger, Alexander

2015-01-01

Despite a pronounced reduction of lethality rates due to upper gastrointestinal bleeding, esophageal variceal bleeding remains a challenge for the endoscopist and still accounts for a mortality rate of up to 40% within the first 6 weeks. A relevant proportion of patients with esophageal variceal bleeding remains refractory to standard therapy, thus making a call for additional tools to achieve hemostasis. Self-expandable metal stents (SEMS) incorporate such a tool. We evaluated a total number of 582 patients admitted to our endoscopy unit with the diagnosis "gastrointestinal bleeding" according to our documentation software between 2011 and 2014. 82 patients suffered from esophageal variceal bleeding, out of which 11 cases were refractory to standard therapy leading to SEMS application. Patients with esophageal malignancy, fistula, or stricture and a non-esophageal variceal bleeding source were excluded from the analysis. A retrospective analysis reporting a series of clinically relevant parameters in combination with bleeding control rates and adverse events was performed. The initial bleeding control rate after SEMS application was 100%. Despite this success, we observed a 27% mortality rate within the first 42 days. All of these patients died due to non-directly hemorrhage-associated reasons. The majority of patients exhibited an extensive demand of medical care with prolonged hospital stay. Common complications were hepatic decompensation, pulmonary infection and decline of renal function. Interestingly, we found in 7 out of 11 patients (63.6%) stent dislocation at time of control endoscopy 24 h after hemostasis or at time of stent removal. The presence of hiatal hernia did not affect obviously stent dislocation rates. Refractory patients had significantly longer hospitalization times compared to non-refractory patients. Self-expandable metal stents for esophageal variceal bleeding seem to be safe and efficient after failed standard therapy. Stent migration appeared to be a common incident that did not lead to reactivation of bleeding in any of our patients. SEMS should be considered a reasonable treatment option for refractory esophageal variceal bleeding after treatment failure of ligature and sclerotherapy and non-availability of or contraindication for other measures (e.g. TIPS).

Axicabtagene Ciloleucel Expanded Access Study

ClinicalTrials.gov

2018-05-29

Relapsed/Refractory Diffuse Large B Cell Lymphoma; Relapsed/Refractory Primary Mediastinal B Cell Lymphoma; Relapsed/Refractory Transformed Follicular Lymphoma; Relapsed/Refractory High-Grade B-Cell Lymphoma

Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

PubMed

Cuq, B; Blois, S L; Mathews, K A

2017-06-01

To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS--A 24-month follow-up in Taiwan.

PubMed

Tsai, Jeng-Dau; Chang, Ying-Chao; Lin, Lung-Chang; Hung, Kun-Long

2016-03-01

Multiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population. We conducted a one-group pretest-posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged <18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children - IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist. Vagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (<12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children. Vagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent-child relationships, especially in young children (<12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age. Copyright © 2015 Elsevier Inc. All rights reserved.

Resuspension and atmospheric transport of radionuclides due to wildfires near the Chernobyl Nuclear Power Plant in 2015: An impact assessment

NASA Astrophysics Data System (ADS)

Evangeliou, N.; Zibtsev, S.; Myroniuk, V.; Zhurba, M.; Hamburger, T.; Stohl, A.; Balkanski, Y.; Paugam, R.; Mousseau, T. A.; Møller, A. P.; Kireev, S. I.

2016-05-01

In April and August 2015, two major fires in the Chernobyl Exclusion Zone (CEZ) caused concerns about the secondary radioactive contamination that might have spread over Europe. The present paper assessed, for the first time, the impact of these fires over Europe. About 10.9 TBq of 137Cs, 1.5 TBq of 90Sr, 7.8 GBq of 238Pu, 6.3 GBq of 239Pu, 9.4 GBq of 240Pu and 29.7 GBq of 241Am were released from both fire events corresponding to a serious event. The more labile elements escaped easier from the CEZ, whereas the larger refractory particles were removed more efficiently from the atmosphere mainly affecting the CEZ and its vicinity. During the spring 2015 fires, about 93% of the labile and 97% of the refractory particles ended in Eastern European countries. Similarly, during the summer 2015 fires, about 75% of the labile and 59% of the refractory radionuclides were exported from the CEZ with the majority depositing in Belarus and Russia. Effective doses were above 1 mSv y-1 in the CEZ, but much lower in the rest of Europe contributing an additional dose to the Eastern European population, which is far below a dose from a medical X-ray.

Resuspension and atmospheric transport of radionuclides due to wildfires near the Chernobyl Nuclear Power Plant in 2015: An impact assessment

PubMed Central

Evangeliou, N.; Zibtsev, S.; Myroniuk, V.; Zhurba, M.; Hamburger, T.; Stohl, A.; Balkanski, Y.; Paugam, R.; Mousseau, T. A.; Møller, A. P.; Kireev, S. I.

2016-01-01

In April and August 2015, two major fires in the Chernobyl Exclusion Zone (CEZ) caused concerns about the secondary radioactive contamination that might have spread over Europe. The present paper assessed, for the first time, the impact of these fires over Europe. About 10.9 TBq of 137Cs, 1.5 TBq of 90Sr, 7.8 GBq of 238Pu, 6.3 GBq of 239Pu, 9.4 GBq of 240Pu and 29.7 GBq of 241Am were released from both fire events corresponding to a serious event. The more labile elements escaped easier from the CEZ, whereas the larger refractory particles were removed more efficiently from the atmosphere mainly affecting the CEZ and its vicinity. During the spring 2015 fires, about 93% of the labile and 97% of the refractory particles ended in Eastern European countries. Similarly, during the summer 2015 fires, about 75% of the labile and 59% of the refractory radionuclides were exported from the CEZ with the majority depositing in Belarus and Russia. Effective doses were above 1 mSv y−1 in the CEZ, but much lower in the rest of Europe contributing an additional dose to the Eastern European population, which is far below a dose from a medical X-ray. PMID:27184191

Cyclosporine treatment of steroid-refractory ulcerative colitis during pregnancy.

PubMed

Branche, Julien; Cortot, Antoine; Bourreille, Arnaud; Coffin, Benoît; de Vos, Martine; de Saussure, Philippe; Seksik, Philippe; Marteau, Philippe; Lemann, Marc; Colombel, Jean-Frédéric

2009-07-01

Cyclosporine is considered a safe and effective treatment of severe steroid-refractory ulcerative colitis (UC). However, few data are available concerning its safety profile in pregnant women. We report here the experience of 5 GETAID centers. In a retrospective study data on patients with severe UC treated with cyclosporine during pregnancy were extracted from medical records of consecutive patients treated between 2001 and 2007. Eight patients (median age 30.5 years old) were identified. At the time of flare-up the median duration of pregnancy was 11.5 weeks of gestation (range 4-25). Seven patients had pancolitis. All patients had more than 3 commonly used clinical and biological severity criteria. Three patients had severe endoscopic lesions and 5 patients had not. All patients received intravenous corticosteroids for at least 7 days before introduction of cyclosporine. Two patients received azathioprine during treatment with cyclosporine. No severe infections or other complications due to treatment were observed. Treatment was effective in 7/8 patients. One patient received infliximab due to cyclosporine therapy failure with a good outcome. No colectomy was performed during pregnancy. Seven pregnancies were conducted to term, but 1 in utero death occurred due to maternal absence of S-protein. Two newborns were premature, including 1 case of hypotrophy. No malformations were observed. In our experience, treatment with cyclosporine for steroid-refractory UC during pregnancy can be considered safe and effective.

Resuspension and atmospheric transport of radionuclides due to wildfires near the Chernobyl Nuclear Power Plant in 2015: An impact assessment.

PubMed

Evangeliou, N; Zibtsev, S; Myroniuk, V; Zhurba, M; Hamburger, T; Stohl, A; Balkanski, Y; Paugam, R; Mousseau, T A; Møller, A P; Kireev, S I

2016-05-17

In April and August 2015, two major fires in the Chernobyl Exclusion Zone (CEZ) caused concerns about the secondary radioactive contamination that might have spread over Europe. The present paper assessed, for the first time, the impact of these fires over Europe. About 10.9 TBq of (137)Cs, 1.5 TBq of (90)Sr, 7.8 GBq of (238)Pu, 6.3 GBq of (239)Pu, 9.4 GBq of (240)Pu and 29.7 GBq of (241)Am were released from both fire events corresponding to a serious event. The more labile elements escaped easier from the CEZ, whereas the larger refractory particles were removed more efficiently from the atmosphere mainly affecting the CEZ and its vicinity. During the spring 2015 fires, about 93% of the labile and 97% of the refractory particles ended in Eastern European countries. Similarly, during the summer 2015 fires, about 75% of the labile and 59% of the refractory radionuclides were exported from the CEZ with the majority depositing in Belarus and Russia. Effective doses were above 1 mSv y(-1) in the CEZ, but much lower in the rest of Europe contributing an additional dose to the Eastern European population, which is far below a dose from a medical X-ray.

Single-side renal sympathetic denervation to treat malignant refractory hypertension in a solitary kidney patient.

PubMed

Ribichini, Flavio; Ferrara, Angela; Pighi, Michele; Pesarini, Gabriele; Gambaro, Alessia; Valvo, Enrico; Lupo, Antonio; Vassanelli, Corrado

2014-12-01

Renal sympathetic denervation (RSD) is emerging as a new therapeutic option for patients with severe hypertension refractory to medical therapy. Patients affected by renovascular or anatomical abnormalities have hitherto been systematically excluded from clinical trials with RSD because of concern about safety and the unknown efficacy of the procedure in this subgroup of patients. We describe the management of a case of RSD in a single-kidney patient with refractory hypertension; the patient had had a previous surgical right nephrectomy for renal cell carcinoma that subsequently required no other oncologic treatment. After multidisciplinary assessment, the patient underwent RSD. The procedure was performed through a 6F femoral access using the Symplicity™ RSD system (Medtronic, Mountain View, CA, USA). Radiofrequency was applied to the renal artery wall in 6 different points under general sedation with midazolam to control back pain caused by the procedure, that was performed without periprocedural complications. The patient was discharged 2 days later after a control of the vascular access site and routine biochemical examinations. The following 9-month follow up showed a significant reduction in blood pressure and stable renal function, without signs of renal damage. Our report confirms the feasibility of RSD in this delicate context, without evident negative effects on kidney function and with a significant reduction in blood pressure. Future studies are needed to fully clarify the value of RSD in single-kidney patients.

Quetiapine for insomnia associated with refractory depression exacerbated by phenelzine.

PubMed

Sokolski, Kenneth N; Brown, Brenda J

2006-03-01

To report the successful treatment of phenelzine-associated insomnia with low-dose quetiapine in a patient with refractory depression. A 42-year-old white man with severe major depression unresponsive to selective serotonin-reuptake inhibitors, bupropion, and tricyclic antidepressants improved following treatment with the monoamine oxidase inhibitor (MAOI) phenelzine. Insomnia, present to a moderate degree prior to antidepressant therapy, worsened markedly following phenelzine treatment and failed to respond to diphenhydramine, temazepam, triazolam, clonazepam, zolpidem, or trazodone given at high therapeutic doses. Sleep disturbance resolved with low-dose (50 mg) adjunctive quetiapine, with no adverse effects. Major depression refractory to standard therapy is a common and serious condition. Some cases respond to MAOIs; however, orthostatic hypotension and insomnia frequently occur. Potentially serious MAOI interactions with psychotropic drugs have raised concerns about combining these agents. In this case, a failure of a number of other medications known to treat MAOI-associated insomnia safely prompted a trial of quetiapine. Despite the possibility that enhanced serotonergic activity might have resulted in serotonin syndrome, no adverse interactions between phenelzine and quetiapine were noted. The use of low-dose, once-daily quetiapine, along with its unique binding properties, may account for its increased safety in combination with phenelzine. This case illustrates that low-dose quetiapine may be an alternative treatment for phenelzine-associated insomnia. Further case reports are needed to establish the safety and effectiveness of combining these agents.

Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

ClinicalTrials.gov

2018-03-28

Breast Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Nodal Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Breast Cancer AJCC v6 and v7

Complementary and alternative medical therapies for interstitial cystitis: an update from the United States

PubMed Central

Atchley, Megan Danielle; Shah, Nima M.

2015-01-01

The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi-disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies. PMID:26816868

Complementary and alternative medical therapies for interstitial cystitis: an update from the United States.

PubMed

Atchley, Megan Danielle; Shah, Nima M; Whitmore, Kristene E

2015-12-01

The diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) has shifted from organ-specific to a multifactorial, multidisciplinary and individualized approach. Patients with refractory and debilitating symptoms may respond to complementary and alternative medical treatments (CAM). Through CAM therapies, practitioners assist the patient to be at the center of their care, empowering them to be emotionally and physically involved. Multi-disciplinary care, including urology, gynecology, gastroenterology, neurology, psychology, physiotherapy and pain medicine, is also identified to be the crux of adequate management of patients with chronic pelvic pain because of its variable etiology. The purpose of this review is to emphasize these changes and discuss management strategies.

Intravenous immunoglobulin use in managing severe, perioperative peristomal pyoderma gangrenosum following subtotal colectomy with end ileostomy for medically refractory chronic ulcerative colitis

PubMed Central

Behm, Kevin; Larson, David W.; Colibaseanu, Dorin

2015-01-01

Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is characterized by painful, necrotic ulcerations occurring in the area surrounding an abdominal stoma. PPG is typically seen in younger patients with active inflammatory bowel disease. The etiology and pathogenesis is largely unknown and risk factors are not well defined. Therapy typically involves a combination of aggressive local wound care and systemic medications. Diagnosis and management of PPG can be difficult and data on treatment are limited. We present a case of severe postoperative peristomal recalcitrant to conventional therapy successfully treated with intravenous immune globulin. PMID:25802252

Algorithms for optimizing the treatment of depression: making the right decision at the right time.

PubMed

Adli, M; Rush, A J; Möller, H-J; Bauer, M

2003-11-01

Medication algorithms for the treatment of depression are designed to optimize both treatment implementation and the appropriateness of treatment strategies. Thus, they are essential tools for treating and avoiding refractory depression. Treatment algorithms are explicit treatment protocols that provide specific therapeutic pathways and decision-making tools at critical decision points throughout the treatment process. The present article provides an overview of major projects of algorithm research in the field of antidepressant therapy. The Berlin Algorithm Project and the Texas Medication Algorithm Project (TMAP) compare algorithm-guided treatments with treatment as usual. The Sequenced Treatment Alternatives to Relieve Depression Project (STAR*D) compares different treatment strategies in treatment-resistant patients.

Single Port Laparoscopic Surgery for Steroid-Refractory Ulcerative Colitis after Kidney Transplantation - Video Vignette.

PubMed

Sparks, Robbie; Cahill, Ronan A

2018-05-19

Immunomodulation has long been a central tenet in both the medical therapy of ulcerative colitis (UC) and in the prevention of organ rejection after renal transplant (RT) with many drugs in common. While severe exacerbation of pre-existing UC is unusual after RT, we recently cared for such a patient whose colitis deteriorated dramatically within the first year of such surgery. While there is anecdotal experience of successful medical escalation to biologic therapy, we thought surgery made better sense and he underwent early single port laparoscopic total colectomy as detailed in the associated video. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Spatio-temporal Hotelling observer for signal detection from image sequences

PubMed Central

Caucci, Luca; Barrett, Harrison H.; Rodríguez, Jeffrey J.

2010-01-01

Detection of signals in noisy images is necessary in many applications, including astronomy and medical imaging. The optimal linear observer for performing a detection task, called the Hotelling observer in the medical literature, can be regarded as a generalization of the familiar prewhitening matched filter. Performance on the detection task is limited by randomness in the image data, which stems from randomness in the object, randomness in the imaging system, and randomness in the detector outputs due to photon and readout noise, and the Hotelling observer accounts for all of these effects in an optimal way. If multiple temporal frames of images are acquired, the resulting data set is a spatio-temporal random process, and the Hotelling observer becomes a spatio-temporal linear operator. This paper discusses the theory of the spatio-temporal Hotelling observer and estimation of the required spatio-temporal covariance matrices. It also presents a parallel implementation of the observer on a cluster of Sony PLAYSTATION 3 gaming consoles. As an example, we consider the use of the spatio-temporal Hotelling observer for exoplanet detection. PMID:19550494

Spatio-temporal Hotelling observer for signal detection from image sequences.

PubMed

Caucci, Luca; Barrett, Harrison H; Rodriguez, Jeffrey J

2009-06-22

Detection of signals in noisy images is necessary in many applications, including astronomy and medical imaging. The optimal linear observer for performing a detection task, called the Hotelling observer in the medical literature, can be regarded as a generalization of the familiar prewhitening matched filter. Performance on the detection task is limited by randomness in the image data, which stems from randomness in the object, randomness in the imaging system, and randomness in the detector outputs due to photon and readout noise, and the Hotelling observer accounts for all of these effects in an optimal way. If multiple temporal frames of images are acquired, the resulting data set is a spatio-temporal random process, and the Hotelling observer becomes a spatio-temporal linear operator. This paper discusses the theory of the spatio-temporal Hotelling observer and estimation of the required spatio-temporal covariance matrices. It also presents a parallel implementation of the observer on a cluster of Sony PLAYSTATION 3 gaming consoles. As an example, we consider the use of the spatio-temporal Hotelling observer for exoplanet detection.

The Use Of Phosphates To Reduce Slag Penetration In Cr203-Based Refractories

DOEpatents

Kwong, Kyei-Sing; Dogan, Cynthia P.; Bennett, James P.; Chinn, Richard E.; Petty, Arthur V.

2004-11-09

A high-chromium refractory material that provides improved resistance to coal slag penetration is presented. The refractory mixture comprises a blend of chromium oxide, aluminum oxide and phosphates. The refractory mixture may be blended with an aggregate and cured. In addition a phosphorous oxide may be blended with chromium oxide and aluminum oxide and additionally an aggregate. The refractory mixture reduces the rate of coal slag penetration into the surface of the cured refractory.

Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

ClinicalTrials.gov

2018-06-28

Constitutional Mismatch Repair Deficiency Syndrome; Lynch Syndrome; Malignant Glioma; Progressive Ependymoma; Progressive Medulloblastoma; Recurrent Brain Neoplasm; Recurrent Childhood Ependymoma; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Refractory Brain Neoplasm; Refractory Diffuse Intrinsic Pontine Glioma; Refractory Ependymoma; Refractory Medulloblastoma

Psychopharmacologic treatment of borderline personality disorder

PubMed Central

Ripoll, Luis H.

2013-01-01

The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning. PMID:24174895

Peripheral neurostimulation for control of intractable occipital neuralgia.

PubMed

Weiner, R L; Reed, K L

1999-07-01

Objective. To present a novel approach for treatment of intractable occipital neuralgia using percutaneous peripheral nerve electrostimulation techniques. Methods. Thirteen patients underwent 17 implant procedures for medically refractory occipital neuralgia. A subcutaneous electrode placed transversely at the level of C1 across the base of the occipital nerve trunk produced paresthesias and pain relief covering the regions of occipital nerve pain Results. With follow-up ranging from 1-½ to 6 years, 12 patients continue to report good to excellent response with greater than 50% pain control and requiring little or no additional medications. The 13th patient (first in the series) was subsequently explanted following symptom resolution. Conclusions. In patients with medically intractable occipital neuralgia, peripheral nerve electrostimulation subcutaneously at the level of C1 appears to be a reasonable alternative to more invasive surgical procedures following failure of more conservative therapies.

A rational approach to the management of chronic migraine.

PubMed

Evans, Randolph W

2013-01-01

About 2% of the adult population has chronic migraine with only 20% diagnosed with this disorder. Those with medication overuse may improve with withdrawal of overuse medications. The intravenous dihydroergotamine regimen usually produces short-term benefit for those with medically refractory chronic migraine. OnabotulinumtoxinA and topiramate have shown efficacy in large placebo-controlled randomized trials. Sodium valproate, gabapentin, tizanidine, amitriptyline, fluoxetine, zonisamide, and possibly memantine may be alternative or possibly combined treatment options but with lesser levels of evidence supporting their use. Preliminary evidence suggests that nerve blocks might be beneficial. Acupuncture, biofeedback, relaxation therapy, and cognitive behavioral therapy might be of benefit. Surgical treatments including bariatric and deactivation of trigger points are of growing interest but not appropriate for most sufferers. Occipital nerve stimulation is a promising treatment with ongoing studies defining its use. © 2013 American Headache Society.

Recurrent vulvovaginitis.

PubMed

Powell, Anna M; Nyirjesy, Paul

2014-10-01

Vulvovaginitis (VV) is one of the most commonly encountered problems by a gynecologist. Many women frequently self-treat with over-the-counter medications, and may present to their health-care provider after a treatment failure. Vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis may occur as discreet or recurrent episodes, and have been associated with significant treatment cost and morbidity. We present an update on diagnostic capabilities and treatment modalities that address recurrent and refractory episodes of VV. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cushing Disease Presenting as Primary Psychiatric Illness: A Case Report and Literature Review.

PubMed

Rasmussen, Sean A; Rosebush, Patricia I; Smyth, Harley S; Mazurek, Michael F

2015-11-01

We report the case of a woman with long-standing refractory depression and psychotic features who was eventually diagnosed with Cushing disease. After surgical treatment of a pituitary adenoma, she experienced gradual psychiatric recovery and was eventually able to discontinue all psychotropic medication. We review the psychiatric components of Cushing disease, implications of psychiatric illnesses for the treatment and prognosis of Cushing disease, and potential pathophysiological mechanisms linking glucocorticoid excess to psychiatric illness.

Plasma Exchange for Refractory MDA5 Myositis and ILD

DTIC Science & Technology

2017-04-26

investigations. S02 ISG/JAC ( Ethics Review) and Public Affa irs (S9 MOW/PA) for review and then forward you a final letter of approval or disapproval. 9...Medical and Technical Papers, for additional information. 11 . The Joint Ethics Regulation (JER) DoD SS00.07 -R, Standards of Conduct. provides...standards of ethical conduct for all DoD personnel and their interactions with other non-DoD entities. organizations, societies. conferences, etc. Part of

Pharmacotherapy of Essential Tremor

PubMed Central

Hedera, Peter; Cibulčík, František; Davis, Thomas L.

2013-01-01

Essential tremor (ET) is a common movement disorder but its pathogenesis remains poorly understood. This has limited the development of effective pharmacotherapy. The current therapeutic armamentaria for ET represent the product of careful clinical observation rather than targeted molecular modeling. Here we review their pharmacokinetics, metabolism, dosing, and adverse effect profiles and propose a treatment algorithm. We also discuss the concept of medically refractory tremor, as therapeutic trials should be limited unless invasive therapy is contraindicated or not desired by patients. PMID:24385718