Gückel, Friedemann J; Brix, Gunnar; Hennerici, Michael; Lucht, Robert; Ueltzhöffer, Christine; Neff, Wolfgang
The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter.
High-resolution nuclear magnetic resonance imaging and single photon emission computerized tomography--cerebral blood flow in a case of pure sensory stroke and mild dementia owing to subcortical arteriosclerotic encephalopathy (Binswanger's disease)
De Chiara, S.; Lassen, N.A.; Andersen, A.R.; Gade, A.; Lester, J.; Thomsen, C.; Henriksen, O.
Pure sensory stroke (PSS) is typically caused by a lacunar infarct located in the ventral-posterior (VP) thalamic nucleus contralateral to the paresthetic symptoms. The lesion is usually so small that it cannot be seen on computerized tomography (CT), as illustrated by our case. In our moderately hypertensive, 72-year-old patient with PSS, CT scanning and conventional nuclear magnetic resonance imaging (NMRI) scanning using a 7-mm-thick slice on a 1.5 Tesla instrument all failed to visualize the thalamic infarct. Using the high-resolution mode with 2-mm slice thickness it was, however, clearly seen. In addition, NMRI unexpectedly showed diffuse periventricular demyelinization as well as three other lacunar infarcts, i.e., findings characteristic of subcortical arteriosclerotic encephalopathy (SAE). This prompted psychometric testing, which revealed signs of mild (subclinical) dementia, in particular involving visiospatial apraxia; this pointed to decreased function of the right parietal cortex, which was structurally intact on CT and NMRI. Single photon emission computerized tomography by Xenon-133 injection and by hexamethyl-propyleneamine-oxim labeled with Technetium-99m showed asymmetric distribution of cerebral blood flow (CBF), with an 18% lower value in the right parietal cortex compared to the left side; this indicated asymmetric disconnection of the cortex by the SAE. Thus, the tomograms of the functional parameter, CBF, correlated better with the deficits revealed by neuropsychological testing than by CT or NMRI.
Fischer, Corinne E.; Qian, Winnie; Schweizer, Tom A.; Millikin, Colleen P.; Ismail, Zahinoor; Smith, Eric E.; Lix, Lisa M.; Shelton, Paul; Munoz, David G.
Background The neuropathological correlates of psychosis in Alzheimer’s disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. Objective To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. Method We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. Results 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. Conclusions Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD. PMID:26682680
Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.
Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio
We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.
Funke, Elisabeth; Kupsch, Andreas; Buchert, Ralph; Brenner, Winfried; Plotkin, Michail
Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson's disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS™ software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.
Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.
Grunt, Sebastian; Steinlin, Maja; Weisstanner, Christian; Schöning, Martin; Mullis, Primus E; Flück, Christa E
Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed. Copyright © 2013 S. Karger AG, Basel.
Arteriosclerosis, particularly aortosclerosis, is the most critical risk factor associated with cardiovascular, cerebrovascular, and renal diseases. The pulsatile hemodynamics in the central aorta consists of blood pressure, flow, and stiffness and substantially differs from the peripheral hemodynamics in muscular arteries. Arteriosclerotic changes with age appear earlier in the elastic aorta, and age-dependent increases in central pulse pressure are more marked than those apparent from brachial pressure measurement. Central pressure can be affected by lifestyle habits, metabolic disorders, and endocrine and inflammatory diseases in a manner different from brachial pressure. Central pulse pressure widening due to aortic stiffening increases left ventricular afterload in systole and reduces coronary artery flow in diastole, predisposing aortosclerotic patients to myocardial hypertrophy and ischemia. The widened pulse pressure is also transmitted deep into low-impedance organs such as the brain and kidney, causing microvascular damage responsible for lacunar stroke and albuminuria. In addition, aortic stiffening increases aortic blood flow reversal, which can lead to retrograde embolic stroke and renal function deterioration. Central pressure has been shown to predict cardiovascular events in most previous studies and potentially serves as a surrogate marker for intervention. Quantitative and comprehensive evaluation of central hemodynamics is now available through various noninvasive pressure/flow measurement modalities. This review will focus on the clinical usefulness and mechanistic rationale of central hemodynamic measurements for cardiovascular risk management.
Arteriosclerosis, particularly aortosclerosis, is the most critical risk factor associated with cardiovascular, cerebrovascular, and renal diseases. The pulsatile hemodynamics in the central aorta consists of blood pressure, flow, and stiffness and substantially differs from the peripheral hemodynamics in muscular arteries. Arteriosclerotic changes with age appear earlier in the elastic aorta, and age-dependent increases in central pulse pressure are more marked than those apparent from brachial pressure measurement. Central pressure can be affected by lifestyle habits, metabolic disorders, and endocrine and inflammatory diseases in a manner different from brachial pressure. Central pulse pressure widening due to aortic stiffening increases left ventricular afterload in systole and reduces coronary artery flow in diastole, predisposing aortosclerotic patients to myocardial hypertrophy and ischemia. The widened pulse pressure is also transmitted deep into low-impedance organs such as the brain and kidney, causing microvascular damage responsible for lacunar stroke and albuminuria. In addition, aortic stiffening increases aortic blood flow reversal, which can lead to retrograde embolic stroke and renal function deterioration. Central pressure has been shown to predict cardiovascular events in most previous studies and potentially serves as a surrogate marker for intervention. Quantitative and comprehensive evaluation of central hemodynamics is now available through various noninvasive pressure/flow measurement modalities. This review will focus on the clinical usefulness and mechanistic rationale of central hemodynamic measurements for cardiovascular risk management. PMID:28603219
Lin, Chou-Ching K
Normal brain function depends on normal neuronal metabolism, which is closely related to systemic homeostasis of metabolites, such as glucose, electrolytes, amino acids and ammonia. "Metabolic encephalopathy" indicates diffuse brain dysfunction caused by various systemic derangements. Electroencephalogram (EEG) is widely used to evaluate metabolic encephalopathy since 1937, when Berger first observed slow brain activity induced by hypoglycemia. EEG is most useful in differentiating organic from psychiatric conditions, identifying epileptogenicity, and providing information about the degree of cortical or subcortical dysfunction. In metabolic encephalopathy, EEG evolution generally correlates well with the severity of encephalopathy. However, EEG has little specificity in differentiating etiologies in metabolic encephalopathy. For example, though triphasic waves are most frequently mentioned in hepatic encephalopathy, they can also be seen in uremic encephalopathy, or even in aged psychiatric patients treated with lithium. Spike-and-waves may appear in hyper- or hypo-glycemia, uremic encephalopathy, or vitamin deficiencies, etc. Common principles of EEG changes in metabolic encephalopathy are (1) varied degrees of slowing, (2) assorted mixtures of epileptic discharge, (3) high incidence of triphasic waves, and (4), as a rule, reversibility after treatment of underlying causes. There are some exceptions to the above descriptions in specific metabolic disorders and EEG manifestations are highly individualized.
Chen, H C; Marsharani, U
Hashimoto's encephalopathy is a subacute condition associated with autoimmune thyroiditis. Its presentation varies from focal neurologic deficits to global confusion. Unlike encephalopathy associated with hypothyroidism, Hashimoto's encephalopathy responds to steroid therapy and not thyroxine replacement.
Lado, Fred A; Rubboli, Guido; Capovilla, Giuseppe; Capovilla, Pippo; Avanzini, Giuliano; Moshé, Solomon L
The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype.
Kim, Jae Woo
This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840
Rodríguez, M; Lindinger, A; Ernsting, N P; Malmsten, M; Siegel, G
The ultrafast dynamics of proteoheparan sulfate (HS-PG) in Krebs blood substitute solution was measured using femtosecond transient absorption spectroscopy after UV excitation. Interacting with blood lipoproteins and Ca(2+) ions, the proteoglycan HS-PG is the key component of the so-called nanoplaque, the earliest stage in atherogenesis. Since tryptophan (Trp) residues are the main optically active parts of HS-PG, analogous measurements were performed on bare Trp in Krebs solution. The comparison reveals distinct differences to main characteristics of the HS-PG broadband absorption spectra. Analyzing the Trp spectra, we show that the results from transient absorption spectroscopy resemble the time constants of the chromophore ultrafast solvation dynamics that have been found by another group using fluorescence up-conversion techniques. Yet, the broadband transient absorption provides more details about the molecular dynamics, including stimulated emission, excited state absorption and resonant energy transfer. Furthermore, the absorption long time dynamics upon adding Ca(2+) to the HS-PG probe were investigated by transient absorption spectroscopy and by surface force and ellipsometry investigations. Notably, a Ca(2+)-induced conformational change responsible for arteriosclerotic nanoplaque formation was detected. Slight differences, which are only visible as broad spectral features in the sub-picosecond time scale, provide a first insight into the molecular formation of nanoplaques in blood vessels, which may yield a better understanding of the genesis of arteriosclerosis.
Bille-Brahe, N E; Engell, H C; Sørensen, M B
This study was undertaken to investigate the hemodynamic effect of prophylactic digitalization before major surgical procedures. Sixteen patients, all admitted for an elective vascular operation for arteriosclerotic disease and all with impaired left ventricular function, were investigated. In half of the patients, digitalis was given before the operation, the other half of the patients served as the control study. The measured parameters were pulmonary artery mean pressure, pulmonary capillary wedge pressure, central venous pressure, mean arterial blood pressure, heart rate, cardiac output, blood volume and arterial, as well as venous, oxygen content. Preoperatively, before digitalization, no significant differences were noted between the two groups at rest and during exercise. Before anesthesia and postoperatively, those given digitalis had improved cardiac function. Those in both groups, however, had a normal hemodynamic response to the surgical trauma. In this study, a definite answer is not provided concerning the usefulness of prophylactic digitalization but an increase in the ability of the digitalized heart to withstand the imposition of a pressure load postoperatively is suggested.
Awazu, Kunio; Fukami, Yuko
Cholesteryl oleate can be selectively removed with an infrared free-electron laser (IFEL). To determine the mechanisms that are involved in the effects induced by IFEL, we compared the effect of FEL exposure and the effect of heating on a sample film and bulk sample of cholesteryl oleate. Heating is regarded as one of the mechanisms by which FEL ablates cholesteryl oleate that has accumulated on the arteriosclerotic region of arterial walls. FEL was applied at a wavelength of 5.75 micrometers and at several average powers (2 - 15 mW). FEL exposure induced melting and a decrease in the number of ester bonds. Using the value of absorbed IFEL- macropulse energy for each power density, the temperature was assumed to be 50 - 300 degree(s)C. In the heating experiment, the sample was heated from room temperature to 500 degree(s)C. Melting and carbonization were observed at 50 degree(s)C and 300 degree(s)C, respectively. We found that FEL exposure and heating each induced melting. FEL exposure induced chemical changes and ablation of cholesteryl oleate, although heating did not. Heating the cholesteryl oleate above 305 degree(s)C induced carbonization, although FEL exposure to the same temperature did not.
Germain, Blair; Maria, Bernard L
Epileptic encephalopathies encompass a heterogeneous group of epilepsy syndromes that manifest with cognitive, behavioral, and neurologic deficits, seizures that are often intractable and multiform, aggressive electroencephalographic paroxysmal activity, and sometimes early death. As more is learned about the etiologies and manifestations of epileptic encephalopathies, progress has been made toward better treatment options. However, there is still a great need for further randomized controlled trials and research to help create clinically effective therapies. The 2015 Neurobiology of Disease in Children symposium, held in conjunction with the 44th annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of epileptic encephalopathy, (3) discuss clinical management and therapies for epileptic encephalopathy, and (4) define future directions of research. This article summarizes the presentations and includes an edited transcript of question-and-answer sessions.
Djelantik, M; Bloemkolk, D; Tijdink, J
Wernicke encephalopathy is an acute neuropsychiatric disease with heterogeneous symptoms, including changes in mental status, ataxia and ocular abnormalities; if left untreated, these symptoms can lead to morbidity and even to mortality. The treatment is thiamine suppletion. Because of the heterogeneity of the symptoms and the high risk of morbidity and mortality if the symptoms are not treated, it is vitally important that on observing a patient's early symptoms the clinician immediately suspects that the symptoms could point to Wernicke encephalopathy.
Yadav, Saroj S.; Lawande, Malini A.; Kulkarni, Shilpa D.; Patkar, Deepak A.
Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is a syndrome of encephalopathy characterized by biphasic seizures and altered consciousness in the acute stage followed in the subacute stage by restricted diffusion in the subcortical white matter on magnetic resonance imaging. The etiology of AESD has been attributed to viral infection like influenza A and human herpes virus 6. The exact pathogenesis of AESD is uncertain. Here we report a case of AESD, diagnosed based on clinicoradiological correlation. PMID:23772250
Bhat, Maya Dattatraya; Prasad, Chandrajit; Tiwari, Sarbesh; Chandra, Sadanandavalli Retnaswami; Christopher, Rita
Ethylmalonic encephalopathy is an inborn error of metabolism characterized by encephalopathy, petechiae chronic diarrhea and acrocyanosis. Imaging findings include patchy signal changes in the basal ganglia, periaqueductal region, subcortical white matter and cerebellum. We describe the novel finding of diffusion restriction in brain lesions, in a proven case of ethylmalonic encephalopathy. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Christova, Peka; James, Lisa M; Engdahl, Brian E; Lewis, Scott M; Carpenter, Adam F; Georgopoulos, Apostolos P
Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in GWI comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon. The highest atrophy was observed in the brainstem, followed by left cerebellum and right thalamus, then by right cerebellum and left thalamus. These findings indicate graded atrophy of regions anatomically connected through the brainstem via the crossed superior cerebellar peduncle (left cerebellum → right thalamus, right cerebellum → left thalamus). This distribution of atrophy, together with the observed systematic reduction in volume of other subcortical areas (basal ganglia, amygdala and diencephalon), resemble the distribution of atrophy seen in toxic encephalopathy (Am J Neuroradiol 13:747-760, 1992) caused by a variety of substances, including organic solvents. Given the potential exposure of Gulf War veterans to "a wide range of biological and chemical agents including sand, smoke from oil-well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide, …" (Institute of Medicine National Research Council. Gulf War and Health: Volume 1. Depleted uranium, pyridostigmine bromide, sarin, and vaccines. National Academies Press, Washington DC, 2000), it is reasonable to suppose that such exposures, alone or in combination, could underlie the subcortical atrophy observed.
Banai, Karen; Hornickel, Jane; Skoe, Erika; Nicol, Trent; Zecker, Steven; Kraus, Nina
Although it is largely agreed that phonological processing deficits are a major cause of poor reading, the neural origins of phonological processing are not well understood. We now show, for the first time, that phonological decoding, measured with a test of single-nonword reading, is significantly correlated with the timing of subcortical auditory processing and also, to a lesser extent, with the robustness of subcortical representation of the harmonic content of speech, but not with pitch encoding. The relationships we observe between reading and subcortical processing fall along a continuum, with poor readers at one end and good readers at the other. These data suggest that reading skill may depend on the integrity of subcortical auditory mechanisms and are consistent with the idea that subcortical representation of the acoustic features of speech may play a role in normal reading as well as in the development of reading disorders. These data establish a significant link between subcortical auditory function and reading, thereby contributing to the understanding of the biological bases of reading. At a more general level, these findings are among the first to establish a direct relationship between subcortical sensory function and a specific cognitive skill (reading). We argue that this relationship between cortical and subcortical function could be shaped during development by the corticofugal pathway and that this cortical-subcortical link could contribute to the phonological processing deficits experienced by poor readers.
Sharf, B.; Bental, E.
A 58 year old woman presenting with abdominal distress and a neuropsychiatric disturbance with evidence of focal neurological deficit is described. A diagnosis of pancreatic encephalopathy was made, and the patient was treated accordingly with pancreatic anti-enzymes. A survey of the literature is presented. Images PMID:5315218
Petrović, Branko; Kostić, Vladimir; Sternić, Nadezda; Kolar, Jovo; Tasić, Nebojsa
Reversible Posterior Leukoencephalopathy Syndrome was introduced into clinical practice in 1996 in order to describe unique syndrome, clinically expressed during hypertensive and uremic encephalopathy, eclampsia and during immunosuppressive therapy . First clinical investigations showed that leucoencephalopathy is major characteristic of the syndrome, but further investigations showed no significant destruction in white cerebral tissue [2, 3, 4]. In majority of cases changes are localise in posterior irrigation area of the brain and in the most severe cases anterior region is also involved. Taking into consideration all above mentioned facts, the suggested term was Posterior Reversible Encephalopathy Syndrome (PRES) for the syndrome clinically expressed by neurological manifestations derived from cortical and subcortical changes localised in posterior regions of cerebral hemispheres, cerebral trunk and cerebellum . Patient, aged 53 years, was re-hospitalized in Cardiovascular Institute "Dediwe" two months after successful aorto-coronary bypass performed in June 2001 due to the chest bone infection. During the treatment of the infection (according to the antibiogram) in September 2001, patient in evening hours developed headache and blurred vision. The recorded blood pressure was 210/120 mmHg so antihypertensive treatment was applied (Nifedipin and Furosemid). After this therapy there was no improvement and intensive headache with fatigue and loss of vision developed. Neurological examination revealed cortical blindness and left hemiparesis. Manitol (20%, 60 ccm every 3 hours) and i.v. Nytroglicerin (high blood pressure). Brain CT revealed oedema of parieto-occipital regions of both hemispheres, more emphasized on the right. (Figure 1a, b, c). There was no sign of focal ischemia even in deeper sections (Figure 1d, e, f). Following three days enormous high blood pressure values were registered. On the fourth day the significant clinical improvement occurred
Pocsay, Gábor; Gazdag, Andrea; Engelhardt, József; Szaniszló, István; Szolnoki, Zoltán; Forczek, Gabriella; Mikló, László
The authors present a case report and review the literature on Hashimoto encephalopathy. The onset of the disease may be marked by focal and then progressively generalized seizures or other neurological symptoms, but a cognitive decline or various psychiatric symptoms may also emerge. High levels of anti-thyroid peroxidase antibodies and/or anti-thyroglobulin antibodies are present in the serum. Corticosteroid treatment usually results in an improvement of symptoms. The syndrome is frequently overlooked and, therefore, the authors strongly recommend testing serum thyroid autoantibodies in cases with encephalopathy of unknown origin independently on the presence of thyroid disease in the patient or family history. The importance of long-term immunosuppressive treatment should also be stressed.
Wabulya, Angela; Lesser, Ronald P; Llinas, Rafael; Kaplan, Peter W
Using electroencephalography (EEG) and histology in patients with diffuse encephalopathy, Gloor et al reported that paroxysmal synchronous discharges (PSDs) on EEG required combined cortical gray (CG) and "subcortical" gray (SCG) matter pathology, while polymorphic delta activity (PDA) occurred in patients with white matter pathology. In patients with encephalopathy, we compared EEG findings and magnetic resonance imaging (MRI) to determine if MRI reflected similar pathological EEG correlations. Retrospective case control study of 52 cases with EEG evidence of encephalopathy and 50 controls without evidence of encephalopathy. Review of clinical, EEG and MRI data acquired within 4 days of each other. The most common EEG finding in encephalopathy was background slowing, in 96.1%. We found PSDs in 0% of cases with the combination of CG and SCG abnormalities. Although 13.5% (n=7) had PSDs on EEG; 3 of these had CG and 4 had SCG abnormalities. A total of 73.1% (38/52) had white matter abnormalities-of these 28.9% (11/38) had PDA. PSDs were found with either CG or "SCG" MRI abnormalities and did not require a combination of the two. In agreement with Gloor et al, PDA occurred with white matter MRI abnormalities in the absence of gray matter abnormalities. © EEG and Clinical Neuroscience Society (ECNS) 2015.
Schneider, K W; Jesse, R; Deeg, P
In a 49-year-old man with crescendo angina, elevated serum cholesterol level and an old posterior myocardial infarction, selective coronary arteriography showed multiple arteriosclerotic aneurysms of the right coronary artery associated with extensive and severe arteriosclerotic disease of the left coronary artery. The patient's mother and brother have both died of a myocardial infarction. Another brother suffers from angina and has documented arteriosclerotic coronary artery disease. Two sisters suffer from angina as well. The possibility of embolization of distal vessels from a friable clot of the aneurysms as a cause of the patient's infarction is discussed. To the best of our knowledge, this is the tenth patient with nonfistulous arteriosclerotic coronary artery aneurysm diagnosed and documented angiographically ante mortem. Including the present case and reviewing the literature, the prevalence of this condition among nonfistulous coronary aneurysms diagnosed ante mortem is 35 per cent and henceforth cannot be regarded as an incidental autopsy finding in cardiac asymptomatic patients.
Schmidt, M; Sitter, T; Lederer, S R; Held, E; Schiffl, H
A 19-year-old patient on chronic ambulatory peritoneal dialysis experienced severe neurologic disturbances caused by uremia. Increased signal intensity was seen bilaterally in the cortical and subcortical areas of the occipital and parietal lobe on cranial magnetic resonance imaging (MRI). Insufficient peritoneal dialysis efficacy was documented and the patient was switched from peritoneal to hemodialysis. Cranial MRI indicated a marked regression of the lesions to nearly normal, confirming the diagnosis of uremic encephalopathy.
Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep
Over the last 10 years the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of twelve autoimmune encephatilic disorders, grouped by syndromes and approached from a clinical perspective. Anti-NMDAR encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420
Penn, A.; Butler, J.; Snyder, C.; Albert, R.E.
Experiments were performed to test whether exposure to mainstream cigarette smoke, without any diet modification, was sufficient to exacerbate arteriosclerotic lesion development in cockerels. Additionally, the experiments were designed to test whether any such effect could be attributed solely to carbon monoxide (CO) in the smoke. Three groups of cockerels (7/group) were exposed 5 days/week in standard inhalation chambers. Each day, one group (smoke) was exposed to smoke produced from the combustion of two packs of cigarettes. A second group (CO) was exposed to CO at levels equivalent to those produced during the combustion of two packs of cigarettes. A third group was sham-exposed. Following sacrifice, the abdominal aorta of each animal was cut into 5 mm segments and the extent of arteriosclerotic lesion development was measured. In smoke animals, compared to those in either of the other two groups, there were more aortic segments with measurable lesions present and the cross-sectional areas of these segments were greater. On a comparative basis, the smoke lesions were three times larger than in either of the other two groups, despite the fact that blood carboxyhemoglobin levels were the same in CO and smoke animals. The location of the lesions and their histological appearance were very similar to those previously described for spontaneous and carcinogen-associated lesions in the cockerel. These results demonstrate that as little as four months of daily exposure to cigarette smoke, in the absence of a cholesterol supplemented diet, can help accelerate arteriosclerotic lesion development. Further, this accelerated development cannot be attributed solely to CO in the smoke.
Hossain, Mohammad A; Jehangir, Waqas; Nai, Qiang; Jessani, Naureen; Khan, Rafay; Yousif, Abdalla; Sen, Shuvendu
Posterior reversible encephalopathy is a complex but well-recognized clinical and radiological entity associated with a variety of benign and malignant conditions including hypertensive encephalopathy, eclampsia, renal failure and immunosuppressive drugs. The pathogenesis is incompletely understood, although it seems to be related to the breakthrough of auto-regulation and endothelial dysfunction. The clinical syndromes typically involve headache, altered mental status, seizures, visual disturbance and other focal neurological signs and radiographically reversible vasogenic subcortical edema without infarction. Here, we report a case of posterior reversible encephalopathy syndrome in a patient with chronic myeloid leukemia who received allogenic bone marrow transplantation (allo-BMT) and immunosuppressive drugs.
Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz
Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223
Albert, Martin L.; Feldman, Robert G.; Willis, Anne L.
Progressive supranuclear palsy (Steele et al.) has a characteristic pattern of dementia: (1) forgetfulness, (2) slowing of thought processes, (3) emotional or personality changes (apathy or depression with occasional outbursts of irritability), and (4) impaired ability to manipulate acquired knowledge. In many neurological disease states associated with subcortical pathology a similar pattern of dementia exists. The neurobehavioural changes of progressive supranuclear palsy thus typify a clinical pattern which may be referred to as subcortical dementia. The subcortical dementias have a striking clinical resemblance to the dementia which occurs after bifrontal lobe disease. However, the subcortical dementias can be clearly distinguished clinically from cortical dementias, other than frontal dementias. We propose as a tentative hypothesis that there may be common pathophysiological mechanisms underlying the subcortical dementias—in particular, disturbances of timing and activation. There are immediate practical implications of this hypothesis: drugs which have an effect on subcortical timing and activating mechanisms may be useful in the treatment of subcortical dementias. PMID:4819905
Wetzburger, C L; Van Regemorter, N; Szliwowski, H B; Abramowicz, M J; Van Bogaert, P
Trichothiodystrophy was diagnosed in a 3-year-old male presenting with speech delay, brittle hair, chronic neutropenia, and a history of febrile convulsions. Cranial magnetic resonance imaging revealed a focal subcortical and periventricular gray matter heterotopia. An acute encephalopathy with status epilepticus and coma occurred when he was 4 years of age during an upper respiratory tract infection. Magnetic resonance imaging revealed multifocal T2-weighted hypersignal lesions involving mainly the thalami, hippocampi, midbrain, and pons. Analysis of cerebrospinal fluid revealed hyperproteinorachia without pleocytosis. Results of an extensive metabolic evaluation of this acute brain injury, resembling the syndrome of acute necrotizing encephalopathy of childhood described in Japan, were negative. Focal neuronal migration disorder and acute encephalopathy with symmetric thalamic involvement are newly described neurologic manifestations of syndromes with trichothiodystrophy, which suggests that these conditions may have a common genetic background.
Tachibana, Yasuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Kusagiri, Kouki; Mori, Kana; Endo, Kazuo; Obata, Takayuki; Inoue, Tomio
Acute encephalopathy is a disease group more commonly seen in children. It is often severe and has neurological sequelae. Imaging is important for early diagnosis and prompt treatment to ameliorate an unfavorable outcome, but insufficient sensitivity/specificity is a problem. To overcome this, a new value (fraction of high b-pair (FH)) that could be processed from clinically acceptable MR diffusion-weighted imaging (DWI) with three different b-values was designed on the basis of a two-compartment model of water diffusion signal attenuation. The purpose of this study is to compare FH with the apparent diffusion coefficient (ADC) regarding the detectability of pediatric acute encephalopathy. We retrospectively compared the clinical DWI of 15 children (1–10 years old, mean 2.34, 8 boys, 7 girls) of acute encephalopathy with another 16 children (1–11 years old, mean 4.89, 9 boys, 7 girls) as control. A comparison was first made visually by mapping FH on the brain images, and then a second comparison was made on the basis of 10 regions of interest (ROIs) set on cortical and subcortical areas of each child. FH map visually revealed diffusely elevated FH in cortical and subcortical areas of the patients with acute encephalopathy; the changes seemed more diffuse in FH compared to DWI. The comparison based on ROI revealed elevated mean FH in the cortical and subcortical areas of the acute encephalopathy patients compared to control with significant difference (P<0.05). Similar findings were observed even in regions where the findings of DWI were slight. The reduction of mean ADC was significant in regions with severe findings in DWI, but it was not constant in the areas with slighter DWI findings. The detectability of slight changes of cortical and subcortical lesions in acute encephalopathy may be superior in FH compared to ADC. PMID:23755112
Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha
The voice is a rich source of information, which the human brain has evolved to decode and interpret. Empirical observations have shown that the human auditory system is especially sensitive to the human voice, and that activity within the voice-sensitive regions of the primary and secondary auditory cortex is modulated by the emotional quality of the vocal signal, and may therefore subserve, with frontal regions, the cognitive ability to correctly identify the speaker's affective state. So far, the network involved in the processing of vocal affect has been mainly characterised at the cortical level. However, anatomical and functional evidence suggests that acoustic information relevant to the affective quality of the auditory signal might be processed prior to the auditory cortex. Here we review the animal and human literature on the main subcortical structures along the auditory pathway, and propose a model whereby the distinction between different types of vocal affect in auditory communication begins at very early stages of auditory processing, and relies on the analysis of individual acoustic features of the sound signal. We further suggest that this early feature-based decoding occurs at a subcortical level along the ascending auditory pathway, and provides a preliminary coarse (but fast) characterisation of the affective quality of the auditory signal before the more refined (but slower) cortical processing is completed.
Bakkaloglu, Sevcan A; Soylemezoglu, Oguz; Buyan, Necla; Oktar, Suna Ozhan; Funahashi, Tohru; Pasaoglu, Hatice; Elhan, Atilla H; Peru, Harun; Hasanoglu, Enver
ADPN, a recently discovered adipocytokine, has attracted great attention because of its anti-atherogenic properties. It was suggested as a protective factor for the cardiovascular system because of its close correlation with several risk factors. Our aim was to investigate serum ADPN levels in pediatric RTR and to document possible relationships between ADPN and arteriosclerotic risk factors. Twenty-one RTR, aged 16.3 +/- 4.0 yr, and 23 healthy age and sex-matched control subjects were enrolled in this study. Serum lipid/lipoprotein fractions, homocysteine and ADPN levels as well as intima-media thickness of the cIMT were determined in both groups. Significantly higher serum ADPN (p < 0.001) and homocysteine (p < 0.05) levels as well as higher cIMT (p < 0.001) were found in RTR compared with the control subjects, whereas apolipoprotein B and lipoprotein (a) levels were not significantly different. HDL cholesterol was positively correlated with log ADPN (r = 0.585, p < 0.01). There were inverse correlations between log time post-transplantation and log ADPN as well as HDL cholesterol (r = -0.438, p < 0.05 and r = -0.578, p < 0.05, respectively). There were no correlation between log ADPN, log homocysteine, log apolipoprotein B, lipoprotein (a), creatinine clearance and cumulative steroid dose. Despite reasonable lipid profiles and remarkably elevated ADPN levels, our pediatric RTR with stable graft function displayed a risk for arteriosclerosis because of increased cIMT and mild hyperhomocysteinemia. Regarding the close positive correlation between ADPN and HDL cholesterol, it could be speculated that ADPN is a novel negative surrogate marker of arteriosclerosis. To our knowledge, this is the only report investigating levels and diverse correlates of ADPN in a pediatric RTR group. Further studies in larger groups of recipients are needed to clarify the interaction between arteriosclerotic risk factors and ADPN.
Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...
Bille-Brahe, N E; Engell, H C; Sørensen, M B
Twenty patients with impaired left ventricular function during exercise, who underwent major vascular surgery for arteriosclerotic disease, were randomly digitalized in the immediate postoperative period. All patients had a smooth postoperative course. Haemodynamic measurements showed improved left ventricular function in those who received digitalis, since 60 min after full digitalization the digitalized patients had a highly significant decrease in pulmonary capillary wedge pressure (PCWP) with unchanged stroke volume index (SVI) and left ventricular stroke work index (LVSWI). The same improvement in cardiac function was present the next morning. The present study provides haemodynamic data in support of clinical studies showing a beneficial effect of prophylactic digitalization in surgical patients with clinical signs of arteriosclerotic heart disease, though not in overt failure.
Laish, Ido; Ben Ari, Ziv
Adult hyperammonaemia is associated with severe liver disease in 90% of cases. In the remainder, noncirrhotic causes should be considered. Measurements of serum ammonia level must be part of the basic work-up in all patients presenting with encephalopathy of unknown origin, even when liver function is normal. Clinician awareness of noncirrhotic hyperammonaemic encephalopathy can contribute to early diagnosis and the initiation of sometimes life-saving treatment. This review focuses on the physiology, aetiology and underlying mechanisms of noncirrhotic hyperammonaemic encephalopathy and discusses the available treatment modalities.
Abletshauser, C; Klüssendorf, D; Schmidt, A; Winkler, K; März, W; Buddecke, E; Malmsten, M; Siegel, G
Proteoheparan sulphate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. As a result of electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing one receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques suggesting that high-density lipoprotein (HDL) has a high binding affinity and a protective effect on interfacial heparan sulphate proteoglycan layers with respect to low-density lipoprotein (LDL) and Ca2+ complexation. Low-density lipoprotein was found to deposit strongly at the proteoheparan sulphate-coated surface, particularly in the presence of Ca2+, apparently through complex formation 'proteoglycan-LDL-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulphate proteoglycan protected against LDL deposition and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL was able to decelerate the ternary complex deposition. Therefore, HDL attached to its proteoglycan receptor sites is thought to raise a multidomain barrier, selection and control motif for transmembrane and paracellular lipoprotein uptake into the arterial wall. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a 'nanoscopic' level under close to physiological conditions. In particular, Ca2+-promoted LDL deposition and the protective effect of HDL even at high Ca2+ and LDL concentrations agree well with previous clinical observations regarding risk
Tanaka, Ryoichi Higashi, Masahiro; Naito, Hiroaki
Purpose. We examined the efficacy of conventional balloon angioplasty and cutting balloon angioplasty (CBA) for the treatment of non-arteriosclerotic renal artery stenosis (RAS). Materials and Methods. From 1993 to 2005, 20 patients underwent 27 percutaneous transluminal renalangioplasty (PTRA) for non-arteriosclerotic RAS (men: 8, women: 12, 25.5 +/- 2 years old; 16 fibromuscular dysplasia (FMD), 4 Takayasu disease). We evaluated the efficacy of CBA by comparing the rate of initial technical success and surgical conversion. Results. Before the clinical authorization of CBA, three of twelve patients (25 %) underwent surgical bypass due to the failure of PTRA due to the hardness of the lesion. After the approval of cutting balloon, we performed CBA in four cases (2 FMD,2 Takayasu disease) to dilate hard lesions, within which a properly sized balloon could not dilate due to their hardness, or to reduce the risk of local dissection. Initial successes were obtained in all patients (8/8, 100%) and none of the patients underwent surgical conversion. Despite of the good initial result, restenosis was observed in three cases within 6 month (3/4, 75 %). Additional interventions were performed in all patients, then, the severity of the restenotic lesion was found not to be exceeded comparing with the initial lesion. Conclusion. The cutting balloon angioplasty may be safe and useful procedure for hard lesions of RAS caused by non-arteriosclerotic disease? especially fibromuscular dysplasia. The cutting balloon may provide the initial success, but the effect on long-term patency is still controversial.
Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna
Metronidazole is a nitroimidazole antimicrobial drug prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system (CNS) toxicity manifesting as metronidazole-induced encephalopathy (MIE). Case report. A 65-year-old woman with hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive encephalopathy to GCS 4 during a 3-week course of metronidazole for cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with symmetrical T2 hyperintensity and generally restricted diffusion in bilateral dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles, internal capsules, and cerebral white matter. Laboratory values did not demonstrate significant electrolyte shifts, and continuous EEG was without seizure. High-dose thiamine was empirically administered. Lumbar puncture was not performed due to coagulopathy and thrombocytopenia. Despite discontinuation of metronidazole and keeping ammonia levels near normal, the patient did not improve. MRI was repeated 1 week after discontinuation of metronidazole. Although there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2 hyperintensity persisted and even progressed in the brainstem, basal ganglia, and subcortical white matter. Petechial hemorrhages developed in bilateral corticospinal tracts and subcortical white matter. T1 hypointensity appeared in the corpus callosum. She was transitioned to comfort measures only and died 12 days later. MIE is an uncommon adverse effect of treatment with metronidazole that characteristically affects the dentate nuclei but may also involve the brainstem, corpus callosum, subcortical white matter, and basal ganglia. While the clinical symptoms and neuroimaging changes are usually reversible, persistent encephalopathy with poor outcome may occur.
Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu
A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.
Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly
Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.
Garvert, Mona M; Friston, Karl J; Dolan, Raymond J; Garrido, Marta I
Human faces may signal relevant information and are therefore analysed rapidly and effectively by the brain. However, the precise mechanisms and pathways involved in rapid face processing are unclear. One view posits a role for a subcortical connection between early visual sensory regions and the amygdala, while an alternative account emphasises cortical mediation. To adjudicate between these functional architectures, we recorded magnetoencephalographic (MEG) evoked fields in human subjects to presentation of faces with varying emotional valence. Early brain activity was better explained by dynamic causal models containing a direct subcortical connection to the amygdala irrespective of emotional modulation. At longer latencies, models without a subcortical connection had comparable evidence. Hence, our results support the hypothesis that a subcortical pathway to the amygdala plays a role in rapid sensory processing of faces, in particular during early stimulus processing. This finding contributes to an understanding of the amygdala as a behavioural relevance detector.
Raue, I; Sauer, I; Voigt, H
In 117 patients with angiographically ascertained arteriosclerotic obstructive disease in the region of pelvis and leg the smoking of cigarettes in a high degree confirmed itself as atherogenic factor of risk. The rate of hypertension of patients with vascular disease was increased in comparison with the average population. In contrast to a control group of test persons who after clinical angiological examination did not give a clue to a vascular disease the patients with vascular diseases shows a significantly higher percentage of radiologically visible calcifications in the region of the abdominal aorta, the iliacal and the peripheral arteries of the legs. The calcification of the vessels were generalized in 85%. Apart from the calcification of the abdominal aorta the sclerosis was visible above all in the vascular are switched after the obstruction. There were no differences between normotonic and hypertonic patients with vascular diseases concerning the state of sclerosis. Clear correlations between the proof of sclerosations of the vessels and the apparative angiologically measurable narrowing of the vascular system are not known. Nevertheless in our opinion the calcification of the arteries of the legs in younger patients may be regarded as a reference to a disturbance of the arterial blood supply which must be clarified. The densitometrically established content of calcium salt in the calcaneus showed a dependance on the formation of collaterals and the state of sclerosis in the corresponding type of obstruction and may give a quantitative measure for the degree of severity of an ischaemic osteoporosis.
Cichoż-Lach, Halina; Michalak, Agata
Hepatic encephalopathy is a medical phenomenon that is described as a neuropsychiatric manifestation of chronic or acute liver disease that is characterized by psychomotor, intellectual and cognitive abnormalities with emotional/affective and behavioral disturbances. This article focuses on the underlying mechanisms of the condition and the differences between hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. Hepatic encephalopathy is a serious condition that can cause neurological death with brain edema and intracranial hypertension. It is assumed that approximately 60%-80% of patients with liver cirrhosis develop hepatic encephalopathy. This review explores the complex mechanisms that lead to hepatic encephalopathy. However, noncirrhotic hyperammonemic encephalopathy is not associated with hepatic diseases and has a completely different etiology. Noncirrhotic hyperammonemic encephalopathy is a severe occurrence that is connected with multiple pathogeneses.
McKee, Ann C; Stern, Robert A; Nowinski, Christopher J; Stein, Thor D; Alvarez, Victor E; Daneshvar, Daniel H; Lee, Hyo-Soon; Wojtowicz, Sydney M; Hall, Garth; Baugh, Christine M; Riley, David O; Kubilus, Caroline A; Cormier, Kerry A; Jacobs, Matthew A; Martin, Brett R; Abraham, Carmela R; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L; Budson, Andrew E; Goldstein, Lee E; Kowall, Neil W; Cantu, Robert C
Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was
McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.
Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I–IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I–III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy
Kaczmarczyk, Aleksandra; Patalong-Ogiewa, M; Krzystanek, E
Hashimoto's encephalopathy (HE) is a rare neuropsychiatric syndrome associated with increased level of antithyroid antibodies. Two types of clinical manifestation can be described: a vasculitic type with stroke like episodes and diffuse progressive type with deterioration of mental function. Neurologic symptoms are present in euthyreosis as well as in thyroid dysfunction. Because of good response to immunosuppressive therapy, the prompt diagnosis and management of HE are crucial. In this study we present the review of current literature and discuss two representative cases.
Posterior reversible encephalopathy syndrome (PRES) is a recently described variant of hypertensive encephalopathy characterized by headache, visual disturbances and altered mental function. Its causes are diverse and in contrast to hypertensive encephalopathy, it can develop without significant elevation of blood pressure. This syndrome is mostly reversible when correctly managed; however, failure to recognize it can lead to cerebral infarction and death.
Scaini, Giselli; Ferreira, Gabriela Kozuchovski; Streck, Emilio Luiz
In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably multifactorial process. Hormonal disturbances, oxidative stress, accumulation of metabolites, imbalance in excitatory and inhibitory neurotransmitters, and disturbance of the intermediary metabolism have been identified as contributing factors. Despite continuous therapeutic progress, most neurological complications of uremia, like uremic encephalopathy, fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation. On the other hand, previous studies showed that antioxidant therapy could be used as an adjuvant therapy for the treatment of these neurological complications.
Terada, T; Higashida, R T; Halbach, V V; Dowd, C F; Nakai, E; Yokote, H; Itakura, T; Hieshima, G B
effective procedure to treat vertebrobasilar ischaemia secondary to high grade arteriosclerotic disease affecting either the distal vertebral or basilar artery regions that do not respond to medical treatment. Images PMID:8774399
Uziel, Graziella; Ghezzi, Daniele; Zeviani, Massimo
Individually rare, when taken as a whole, genetic inborn errors of metabolism (IEM) account for a significant proportion of early onset encephalopathy. Prompt diagnosis is crucial to assess appropriate investigation and can sometimes warrant successful therapy. Recent improvements in technology and expansion of knowledge on the biochemical and molecular basis of these disorders allow astute child neurologists and paediatricians to improve the early diagnosis of these genetically determined defects. However, because of rarity and heterogeneity of these disorders, IEM encephalopathies are still a formidable challenge for most physicians. The most frequent cause of childhood IEM encephalopathy is mitochondrial disease, whose biochemical 'signature' is faulty energy supply due to defects of the last component of the oxidative pathways residing within mitochondria, i.e. the mitochondrial respiratory chain. Copyright © 2011. Published by Elsevier Ltd.
Zamora Nava, Luis Eduardo; Torre Delgadillo, Aldo
The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.
Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of
Mohnot, D; Snead, O C; Benton, J W
Among 287 children with burns treated over a recent two-year period, 13 (5%) showed evidence of encephalopathy. The major clinical symptoms were an altered sensorium and seizures. The majority of symptoms began later than 48 hours after the burn and were accompanied by multiple metabolic aberrations including hypocalcemia. Three children had a relapsing course, and 1 had temporarily enlarged cerebral ventricles. Eleven children improved to normal. In the majority of instances, burn encephalopathy probably reflects central nervous system dysfunction resulting from complex metabolic, hematological, and hemodynamic abnormalities rather than from a single metabolic abnormality.
Ciabarra, A M; Elkind, M S; Roberts, J K; Marshall, R S
Stuttering is an uncommon presentation of acute stroke. Reported cases have often been associated with left sided cortical lesions, aphasia, and difficulties with other non-linguistic tests of rhythmic motor control. Three patients with subcortical lesions resulting in stuttering are discussed. In one patient the ability to perform time estimations with a computerised repetitive time estimation task was characterised. One patient had a pontine infarct with clinical evidence of cerebellar dysfunction. A second patient had a left basal ganglionic infarct and a disruption of timing estimation. A third patient had a left subcortical infarct and a mild aphasia. These findings expand the reported distribution of infarction that can result in acquired stuttering. Subcortical mechanisms of speech control and timing may contribute to the pathophysiology of acquired stuttering.
Waghray, Abhijeet; Waghray, Nisheet; Mullen, Kevin
Hepatic encephalopathy is a reversible progressive neuropsychiatric disorder that encompasses a wide clinical spectrum. Covert hepatic encephalopathy is defined as patients with minimal hepatic encephalopathy and Grade I encephalopathy by West-Haven Criteria. Terminology such as "sub-clinical", "latent", and "minimal" appear to trivialize the disease and have been replaced by the term covert. The lack of clinical signs means that covert hepatic encephalopathy is rarely recognized or treated outside of clinical trials with options for therapy based on patients with episodic hepatic encephalopathy. This review discusses the current available options for therapy in covert hepatic encephalopathy and focuses on non-absorbable disacharides (lactulose or lactitol), antibiotics (rifaximin), probiotics/synbiotics and l-ornithine-l-aspartate.
Adikari, Madura; Priyangika, Dilani; Marasingha, Indika; Thamotheram, Sharmila; Premawansa, Gayani
Posterior reversible encephalopathy syndrome is a clinical radiographic syndrome of heterogeneous etiologies. Developing hypertensive encephalopathy following post-streptococcal glomerulonephritis is a known but uncommon manifestation and developing posterior reversible encephalopathy syndrome in such a situation is very rare. We report a case with contrast-enhanced computed tomography and magnetic resonance imaging findings of posterior reversible encephalopathy syndrome in the background of acute post-streptococcal glomerulonephritis. A thirteen-year-old Sri Lankan boy presented with a focal fit by way of secondary generalization with duration of 10 minutes, and developed 2 similar fits subsequently following admission. He later developed severe hypertension with evidence of glomerulonephritis, which was diagnosed as acute post-streptococcal glomerulonephritis. A contrast-enhanced computed tomography imaging of brain done on day-3 revealed non-enhancing low-attenuating areas in fronto-parietal regions. A T2 weighted film of magnetic resonance imaging was done on day-10 of the admission and found to have linier sub-cortical hyper intensities in both parietal regions which were compatible with the radiological diagnosis of posterior reversible encephalopathy syndrome. Post-streptococcal glomerulonephritis is an important cause of acute nephritic syndrome especially in children. This case report illustrates a rare association of posterior reversible encephalopathy syndrome in a patient with post-streptococcal glomerulonephritis.
Masdeu, J.C.; Yudd, A.; Van Heertum, R.L.; Grundman, M.; Hriso, E.; O'Connell, R.A.; Luck, D.; Camli, U.; King, L.N. )
Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.
Wright, G.; Chattree, A.; Jalan, R.
Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease. PMID:21994873
Bovine spongiform encephalopathy (BSE) is caused by a novel contagion, known to as a prion. Prions are proteins capable of converting a normal cellular protein into a prion, thereby propagating an infection. BSE is the first known prion zoonotic. As such it has attracted broad scientific and, to a r...
Millichap, John J.; Park, Kristen L.; Tsuchida, Tammy; Ben-Zeev, Bruria; Carmant, Lionel; Flamini, Robert; Joshi, Nishtha; Levisohn, Paul M.; Marsh, Eric; Nangia, Srishti; Narayanan, Vinodh; Ortiz-Gonzalez, Xilma R.; Patterson, Marc C.; Pearl, Phillip L.; Porter, Brenda; Ramsey, Keri; McGinnis, Emily L.; Taglialatela, Maurizio; Tracy, Molly; Tran, Baouyen; Venkatesan, Charu; Weckhuysen, Sarah
Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy. PMID:27602407
Muramatsu, Chisako; Takahashi, Ryo; Hara, Takeshi; Hayashi, Tatsuro; Katsumata, Akitoshi; Zhou, Xiangrong; Fujita, Hiroshi
Several studies have reported the presence of carotid artery calcifications (CACs) on dental panoramic radiographs (DPRs) as a possible sign of arteriosclerotic diseases. However, CACs are not easily visible at the common window level for dental examinations, and dentists, in general, are not looking for CACs. Computerized detection of CACs may help dentists in referring patients with a risk of arteriosclerotic diseases to have a detailed examination at a medical clinic. Downside of our previous method was a relatively large number of false positives (FPs). In this study, we attempted to reduce FPs by including an additional feature and selecting effective features for the classifier. A hundred DPRs including 34 cases with calcifications were included. Initial candidates were detected by thresholding the output of top-hat operation. For each candidate, 10 features and a new feature characterizing the relative position of a CAC with reference to the lower mandible edge were determined. After the rule-based FP reduction, candidates were classified into CACs and FPs by a support vector machine. Based on the leave-one-out cross-validation evaluations, an average number of FPs was 3.1 per image at 90.4% sensitivity using seven features selected. Compared to our previous method, the number of FPs was reduced by 38% at the same sensitivity level. The proposed method has a potential in identifying patients with a risk of arteriosclerosis early via general dental examinations.
Wan, Ping; Chen, Xuhui; Zhu, Lequn; Xu, Shuangjin; Huang, Li; Li, Xiangcui; Ye, Qing; Ding, Ruiying
Studies have recognized that the damage in the subcortical and supratentorial regions may affect voluntary and involuntary aspects of the swallowing function. The current study attempted to explore the dysphagia characteristics in patients with subcortical and supratentorial stroke. Twelve post first or second subcortical and supratentorial stroke patients were included in the study. The location of the stroke was ascertained by computed tomography and magnetic resonance imaging. The characteristics of swallowing disorder were assessed by video fluoroscopic swallowing assessment/fiberoptic endoscopic evaluation of swallowing. The following main parameters were analyzed: oral transit time, pharyngeal delay time, presence of cricopharyngeal muscle achalasia (CMA), distance of laryngeal elevation, the amounts of vallecular residue and pyriform sinus residue (PSR), and the extent of pharyngeal contraction. Eighty-three percent of the 12 patients were found suffering from pharyngeal dysphagia, with 50% having 50%-100% PSRs, 50% having pharyngeal delay, and 41.6% cases demonstrating CMA. Simple regression analysis showed PSRs were most strongly associated with CMA. Pharyngeal delay in the study can be caused by infarcts of basal ganglia/thalamus, infarcts of sensory tract, infarcts of swallowing motor pathways in the centrum semiovale, or a combination of the three. Subcortical and supratentorial stroke may result in pharyngeal dysphagia such as PSR and pharyngeal delay. PSR was mainly caused by CMA. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Kang, Xiaojian; Herron, Timothy J; Ettlinger, Marc; Woods, David L
Previous research studies have reported many hemispherical asymmetries in cortical and subcortical anatomy, but only a subset of findings is consistent across studies. Here, we used improved Freesurfer-based automated methods to analyse the properties of the cortex and seven subcortical structures in 138 young adult subjects. Male and female subjects showed similar hemispheric asymmetries in gyral and sulcal structures, with many areas associated with language processing enlarged in the left hemisphere (LH) and a number of areas associated with visuospatial processing enlarged in the right hemisphere (RH). In addition, we found greater (non-directional) cortical asymmetries in subjects with larger brains. Asymmetries in subcortical structures included larger LH volumes of thalamus, putamen and globus pallidus and larger RH volumes of the cerebellum and the amygdala. We also found significant correlations between the subcortical structural volumes, particularly of the thalamus and cerebellum, with cortical area. These results help to resolve some of the inconsistencies in previous studies of hemispheric asymmetries in brain anatomy.
Markus, Hugh Stephen
Background Migraine is common in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) but its treatment responses are not well described, and its relationship to stroke risk unknown. Encephalopathy is a less common presentation; it has been suggested it is related to migraine. We characterised migraine patterns and treatment responses in CADASIL, and examined associations between migraine and both stroke risk and encephalopathy. Methods 300 symptomatic CADASIL patients were prospectively recruited from a national referral clinic over a nineteen year period, from 1996 to 2015. Data was collected using a standardised questionnaire. Migraine was classified according to the International Classification of Headache Disorders, 3rd edition (beta version). A cross-sectional analysis was carried out on the data collected. Results Migraine was present in 226 (75.3%), and the presenting feature in 203 (67.7%). It was usually accompanied by aura (89.8%). Patients showed variable responses to a variety of drugs for migraine. Of 24 given triptans, 45.5% had consistent or partial responses. None had complications following triptans. Thirty-three (11.0%) patients experienced encephalopathy lasting on average 8.1 ± 3.4 days. Patients with migraine with aura had higher odds of encephalopathy (OR = 5.4; 95%CI 1.6–28.4; p = 0.002). Patients with confusional aura had higher odds of encephalopathy than those with other aura types (OR = 2.5, 95%CI = 1.0–5.8, p = 0.04). There was also no increase in risk of encephalopathy with sex or age at onset of migraine. Migraineurs had a lower stroke risk than non-migraineurs (HR = 0.46, 95%CI 0.3–0.6, p = 2.1x10-6). Conclusions Migraine with aura is a prominent feature of CADASIL. Treatment responses are similar to those seen in the general migraine population and no complications were observed with triptans. Migraine with aura was associated with increased risk of encephalopathy suggesting
Tan, Rhea Yan Ying; Markus, Hugh Stephen
Migraine is common in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) but its treatment responses are not well described, and its relationship to stroke risk unknown. Encephalopathy is a less common presentation; it has been suggested it is related to migraine. We characterised migraine patterns and treatment responses in CADASIL, and examined associations between migraine and both stroke risk and encephalopathy. 300 symptomatic CADASIL patients were prospectively recruited from a national referral clinic over a nineteen year period, from 1996 to 2015. Data was collected using a standardised questionnaire. Migraine was classified according to the International Classification of Headache Disorders, 3rd edition (beta version). A cross-sectional analysis was carried out on the data collected. Migraine was present in 226 (75.3%), and the presenting feature in 203 (67.7%). It was usually accompanied by aura (89.8%). Patients showed variable responses to a variety of drugs for migraine. Of 24 given triptans, 45.5% had consistent or partial responses. None had complications following triptans. Thirty-three (11.0%) patients experienced encephalopathy lasting on average 8.1 ± 3.4 days. Patients with migraine with aura had higher odds of encephalopathy (OR = 5.4; 95%CI 1.6-28.4; p = 0.002). Patients with confusional aura had higher odds of encephalopathy than those with other aura types (OR = 2.5, 95%CI = 1.0-5.8, p = 0.04). There was also no increase in risk of encephalopathy with sex or age at onset of migraine. Migraineurs had a lower stroke risk than non-migraineurs (HR = 0.46, 95%CI 0.3-0.6, p = 2.1x10-6). Migraine with aura is a prominent feature of CADASIL. Treatment responses are similar to those seen in the general migraine population and no complications were observed with triptans. Migraine with aura was associated with increased risk of encephalopathy suggesting they may share pathophysiological mechanisms
Silver, B E; Bean, C S
Cat scratch disease is usually benign, self-limited and without sequelae. Margileth has established four clinical criteria, three of which must be satisfied to make the diagnosis: 1) a history of animal exposure, usually kitten, with primary skin or ocular lesions; 2) regional chronic adenopathy without other apparent cause; 3) a positive cat scratch disease antigen skin test; and 4) lymph node biopsy demonstrating noncaseating granulomas and germinal center hyperplasia. Central nervous system involvement in cat scratch disease has been previously reported, although it is extremely uncommon. In a several-month period, we encountered two cases of cat scratch disease complicated by encephalopathy. The intents of this paper are twofold: 1) to briefly review the current literature on cat scratch disease, 2) to demonstrate that cat scratch disease complicated by encephalopathy presents acutely with seizures, posturing and coma and resolves rapidly with supportive care.
Hypertensive encephalopathy is one cause of posterior reversible encephalopathy syndrome. Hypertensive encephalopathy and cerebral infarction have only been reported in a few individual case reports. A 51-year-old woman presented with hypertensive encephalopathy. T2-weighted images from magnetic resonance imaging showed hyperintense lesions in both occipital and parietal lobes. Diffusion-weighted imaging showed that this represented cytotoxic oedema and perfusion magnetic resonance imaging revealed reduced blood volume and flow. The magnetic resonance imaging was repeated 5 months later and subtotal regression of theT2-hyperintensity had occurred. However, small bilateral infarcts were seen on T1-weighted images. Perfusion magnetic resonance imaging presented reduced blood volume and flow on the right side. The patient in this report had posterior reversible encephalopathy syndrome caused by hypertensive encephalopathy. Magnetic resonance imaging of the brain showed bilateral cytotoxic oedema that partially resolved and resulted in small infarcts. The imaging findings are compatible with posterior reversible encephalopathy syndrome with subtotal resolution and infarct evolution. The case report suggests that the presence of hypertensive encephalopathy and posterior reversible encephalopathy syndrome should alert clinicians and lead to prompt treatment in order to prevent cerebral damage.
Zhou, J Y; Xu, B; Lopes, J; Blamoun, J; Li, L
Hashimoto encephalopathy (HE) presents as an encephalopathy without central nervous system infection or tumor. HE is associated with autoimmune thyroiditis and is thus considered to be an autoimmune disorder. The prevalence of HE is low, but death and status epilepticus have been reported. HE manifests with a wide range of symptoms that include behavioral changes and confusion. Elevated thyroid antibodies are present in the majority of cases and are required for the diagnosis of HE. Normal brain MRI findings are found in the majority of patients diagnosed with HE. The most consistent CSF abnormality noted in HE patients is the presence of elevated protein. Most HE patients respond well to steroid therapy. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. In conclusion, it is now generally accepted that the diagnosis of HE must include encephalopathy characterized by cognitive impairment associated with psychiatric features, such as hallucinations, delusions, and paranoia. Autoimmune encephalitis and prion disease should be considered in the differential diagnosis due to the similarity of the clinical features of these conditions to those of HE. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Understanding and appreciating the science of pharmacoeconomics have become even more important for health care providers and insurers during the recent economic downturn. Evaluating the true costs of any disease is complex; both direct costs, such as costs of drug therapy and the provision of care, and indirect costs, such as lost earnings and reduced quality of life, must be taken into account. With chronic liver disease, the most recent data indicate that direct costs were more than $2 billion whereas indirect costs were more than $450 million. Hepatic encephalopathy, a common complication of chronic liver disease, contributes to this economic burden. Although patients' length of stay during hospitalization for hepatic encephalopathy decreased from almost 9 days to 6 days (and has remained stable over the past few years) from 1993 to 2007, hospitalization costs rose from $13,000 to $30,000/hospital stay. In addition, 22% of patients were discharged directly to nursing homes or rehabilitation centers, which increases total costs. When assessing therapy for hepatic encephalopathy, it is important to consider the total costs of the disease, not just treatment costs. Although more expensive on a daily basis than lactulose, rifaximin has been shown to reduce hospitalization rates, has a better adverse-effect profile, and increases patient compliance. One study found that rifaximin produced a cost savings/patient/year of more than $3000 over lactulose therapy.
Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal
SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258
D'Este, Elisa; Kamin, Dirk; Velte, Caroline; Göttfert, Fabian; Simons, Mikael; Hell, Stefan W
Superresolution fluorescence microscopy recently revealed a ~190 nm periodic cytoskeleton lattice consisting of actin, spectrin, and other proteins underneath the membrane of cultured hippocampal neurons. Whether the periodic cytoskeleton lattice is a structural feature of all neurons and how it is modified when axons are ensheathed by myelin forming glial cells is not known. Here, STED nanoscopy is used to demonstrate that this structure is a commonplace of virtually all neuron types in vitro. To check how the subcortical meshwork is modified during myelination, we studied sciatic nerve fibers from adult mice. Periodicity of both actin and spectrin was uncovered at the internodes, indicating no substantial differences between unmyelinated and myelinated axons. Remarkably, the actin/spectrin pattern was also detected in glial cells such as cultured oligodendrocyte precursor cells. Altogether our work shows that the periodic subcortical cytoskeletal meshwork is a fundamental characteristic of cells in the nervous system and is not a distinctive feature of neurons, as previously thought.
Jung, Rex E.; Ryman, Sephira G.; Vakhtin, Andrei A.; Carrasco, Jessica; Wertz, Chris; Flores, Ranee A.
The study of individual differences encompasses broad constructs including intelligence, creativity, and personality. However, substantially less research is devoted to the study of specific aptitudes in spite of their importance to educational, occupational, and avocational success. We sought to determine subcortical brain structural correlates of several broad aptitudes including Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N = 107), healthy, young (age range = 16–29) cohort. Subcortical volumes were measured using an automated technique (FreeSurfer) across structures including bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus, amygdala, and five equal regions of the corpus callosum. We found that performance on measures of each aptitude was predicted by different subcortical structures: Math – higher right nucleus accumbens volume; Vocabulary – higher left hippocampus volume; Paper Folding – higher right thalamus volume; Foresight – lower right thalamus and higher mid anterior corpus callosum volume; Inductive Reasoning – higher mid anterior corpus callosum volume. Our results support general findings, within the cognitive neurosciences, showing lateralization of structure-function relationships, as well as more specific relationships between individual structures (e.g., left hippocampus) and functions relevant to particular aptitudes (e.g., Vocabulary). PMID:24586770
Jung, Rex E; Ryman, Sephira G; Vakhtin, Andrei A; Carrasco, Jessica; Wertz, Chris; Flores, Ranee A
The study of individual differences encompasses broad constructs including intelligence, creativity, and personality. However, substantially less research is devoted to the study of specific aptitudes in spite of their importance to educational, occupational, and avocational success. We sought to determine subcortical brain structural correlates of several broad aptitudes including Math, Vocabulary, Foresight, Paper Folding, and Inductive Reasoning in a large (N = 107), healthy, young (age range = 16-29) cohort. Subcortical volumes were measured using an automated technique (FreeSurfer) across structures including bilateral caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus, amygdala, and five equal regions of the corpus callosum. We found that performance on measures of each aptitude was predicted by different subcortical structures: Math--higher right nucleus accumbens volume; Vocabulary--higher left hippocampus volume; Paper Folding--higher right thalamus volume; Foresight--lower right thalamus and higher mid anterior corpus callosum volume; Inductive Reasoning--higher mid anterior corpus callosum volume. Our results support general findings, within the cognitive neurosciences, showing lateralization of structure-function relationships, as well as more specific relationships between individual structures (e.g., left hippocampus) and functions relevant to particular aptitudes (e.g., Vocabulary).
Iverson, Grant L; Gardner, Andrew J; McCrory, Paul; Zafonte, Ross; Castellani, Rudy J
Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features. Copyright © 2015 Elsevier Ltd. All rights reserved.
Sudulagunta, Sreenivasa Rao; Sodalagunta, Mahesh Babu; Kumbhat, Monica; Settikere Nataraju, Aravinda
Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome characterized by a headache, seizures, altered mental status and visual loss and characterized by white matter vasogenic edema affecting the posterior occipital and parietal lobes of the brain predominantly. This clinical syndrome is increasingly recognized due to improvement and availability of brain imaging specifically magnetic resonance imaging (MRI). A 35-year-old female with the history of unsafe abortion and massive blood transfusion 10 days ago was brought to the emergency room with three episodes of generalized tonic-clonic seizures, urinary incontinence and altered sensorium since 3 hours. MRI brain showed bilateral occipital, parietal, frontal cortex and subcortical white matter T2/Fluid-attenuated inversion recovery hyperintensities, suggestive of PRES. The patient improved after management with intravenous fluids, antibiotics, antiepileptics and monitoring of blood pressure. If recognized and treated early, the clinical syndrome commonly resolves within a week. PRES can be a major problem in rapid and massive blood transfusion. A high index of suspicion and prompt treatment can reduce morbidity, mortality and pave the path for early recovery.
Davis, Richard L.; Holohan, Peter D.; Shrimpton, Antony E.; Tatum, Arthur H.; Daucher, John; Collins, George H.; Todd, Robert; Bradshaw, Charles; Kent, Paul; Feiglin, David; Rosenbaum, Arthur; Yerby, Mark S.; Shaw, Cheng-Mei; Lacbawan, Felicitas; Lawrence, Daniel A.
We report on a new familial neurodegenerative disease with associated dementia that has presented clinically in the fifth decade, in both genders, and in each of several generations of a large family from New York State—a pattern of inheritance consistent with an autosomal dominant mode of transmission. A key pathological finding is the presence of neuronal inclusion bodies distributed throughout the gray matter of the cerebral cortex and in certain subcortical nuclei. These inclusions are distinct from any described previously and henceforth are identified as Collins bodies. The Collins bodies can be isolated by simple biochemical procedures and have a surprisingly simple composition; neuroserpin (a serine protease inhibitor) is their predominant component. An affinity-purified antibody against neuroserpin specifically labels the Collins bodies, confirming their chemical composition. Therefore, we propose a new disease entity—familial encephalopathy with neuroserpin inclusion bodies (FENIB). The conclusion that FENIB is a previously unrecognized neurodegenerative disease is supported by finding Collins bodies in a small kindred from Oregon with familial dementia who are unrelated to the New York family. The autosomal dominant inheritance strongly suggests that FENIB is caused by mutations in the neuroserpin gene, resulting in intracellular accumulation of the mutant protein. PMID:10595921
Davis, R L; Holohan, P D; Shrimpton, A E; Tatum, A H; Daucher, J; Collins, G H; Todd, R; Bradshaw, C; Kent, P; Feiglin, D; Rosenbaum, A; Yerby, M S; Shaw, C M; Lacbawan, F; Lawrence, D A
We report on a new familial neurodegenerative disease with associated dementia that has presented clinically in the fifth decade, in both genders, and in each of several generations of a large family from New York State-a pattern of inheritance consistent with an autosomal dominant mode of transmission. A key pathological finding is the presence of neuronal inclusion bodies distributed throughout the gray matter of the cerebral cortex and in certain subcortical nuclei. These inclusions are distinct from any described previously and henceforth are identified as Collins bodies. The Collins bodies can be isolated by simple biochemical procedures and have a surprisingly simple composition; neuroserpin (a serine protease inhibitor) is their predominant component. An affinity-purified antibody against neuroserpin specifically labels the Collins bodies, confirming their chemical composition. Therefore, we propose a new disease entity-familial encephalopathy with neuroserpin inclusion bodies (FENIB). The conclusion that FENIB is a previously unrecognized neurodegenerative disease is supported by finding Collins bodies in a small kindred from Oregon with familial dementia who are unrelated to the New York family. The autosomal dominant inheritance strongly suggests that FENIB is caused by mutations in the neuroserpin gene, resulting in intracellular accumulation of the mutant protein.
Howell, Katherine B.; McMahon, Jacinta M.; Carvill, Gemma L.; Tambunan, Dimira; Mackay, Mark T.; Rodriguez-Casero, Victoria; Webster, Richard; Clark, Damian; Freeman, Jeremy L.; Calvert, Sophie; Olson, Heather E.; Mandelstam, Simone; Poduri, Annapurna; Mefford, Heather C.; Harvey, A. Simon
Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1–4 in 8, week 2–6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile–onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control. PMID:26291284
Cirelli, A; Ciardi, M; Salotti, A; Rossi, F
The authors describe the first case in literature of Gerstmann's syndrome (agraphia, acalculia, finger agnosia) occurred in HIV correlated encephalopathy developed as the first severe manifestation of HIV infection in a patient with prevalent white matter neuroradiologic alterations. The PDL rapidly extended from the left subcortical parietal-occipital regions to the pre-rolandic one, with subsequent involvement of the corpus calosum splenium and the bilateral temporal lobes white matter. The authors indicate the extent of the lesions and the involvement of the interhemispheric connection fibres as the pathogenetic mechanism of the "Gerstmann syndrome", that until today has not been reported in the literature of the wide variety of AIDS dementia complex. The administration of 1 g of zidovudine for about 9 months did not avoid the establishing of the neurologic damage, but the sudden suspension of the drug could have enhanced the exacerbation of inflammation and the involvement of areas whose lesion is classically believed responsible for cognitive impairment.
Studyvin, Sarah; Al-Halawani, Moh’d; Amireh, Sawsan; Thawabi, Mohammad
Posterior reversible encephalopathy syndrome (PRES) is characterized by rapid onset of symptoms including headache, seizures, altered consciousness, and visual disturbance, as well as radiologic findings of focal reversible vasogenic edema. Multiple visual disturbances have been described in PRES, such as hemianopia, visual neglect, auras, visual hallucinations, and cortical blindness. However, horizontal gaze palsy has not been previously reported. We report a 72-year-old female who presented with blurred vision, severe headache, lethargy, and later developed seizures. She was found to have left horizontal gaze palsy with intact vestibulo-ocular reflex. Brain magnetic resonance imaging (MRI) showed severe edema throughout the subcortical white matter, and signal in the posterior parietal and occipital lobes. She was diagnosed with PRES associated with supranuclear gaze palsy. PMID:28361069
Méndez, Marta; Fidalgo, Camino; Aller, María Ángeles; Arias, Jaime; Arias, Jorge L.
Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups. PMID:23573412
Krizman, Jennifer; Skoe, Erika; Kraus, Nina
Sex differences have been demonstrated in the peripheral auditory system as well as in higher-level cognitive processing. Here, we aimed to determine if the subcortical response to a complex auditory stimulus is encoded differently between the sexes. Using electrophysiological techniques, we assessed the auditory brainstem response to a synthesized stop-consonant speech syllable [da] in 76 native-English speaking, young adults (38 female). Timing and frequency components of the response were compared between males and females to determine which aspects of the response are affected by sex. A dissimilarity between males and females was seen in the neural response to the components of the speech stimulus that change rapidly over time; but not in the slower changing, lower frequency information in the stimulus. We demonstrate that, in agreement with the click-evoked brainstem response, females have earlier peaks relative to males in the subcomponents of the response representing the onset of the speech sound. In contrast, the response peaks comprising the frequency-following response, which encode the fundamental frequency (F(0)) of the stimulus, as well as the spectral amplitude of the response to the F(0), is not affected by sex. Notably, the higher-frequency elements of the speech syllable are encoded differently between males and females, with females having greater representation of spectrotemporal information for frequencies above the F(0). Our results provide a baseline for interpreting the higher incidence of language impairment (e.g. dyslexia, autism, specific language impairment) in males, and the subcortical deficits associated with these disorders. These results parallel the subcortical encoding patterns that are documented for good and poor readers in that poor readers differ from good readers on encoding fast but not slow components of speech. This parallel may thus help to explain the higher incidence of reading impairment in males compared to females
Price, Raymond S; Kasner, Scott E
The definition of hypertension has continuously evolved over the last 50 years. Hypertension is currently defined as a blood pressure greater than 140/90mmHg. One in every four people in the US has been diagnosed with hypertension. The prevalence of hypertension increases further with age, affecting 75% of people over the age of 70. Hypertension is by far the most common risk factor identified in stroke patients. Hypertension causes pathologic changes in the walls of small (diameter<300 microns) arteries and arterioles usually at short branches of major arteries, which may result in either ischemic stroke or intracerebral hemorrhage. Reduction of blood pressure with diuretics, β-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors have all been shown to markedly reduce the incidence of stroke. Hypertensive emergency is defined as a blood pressure greater than 180/120mmHg with end organ dysfunction, such as chest pain, shortness of breath, encephalopathy, or focal neurologic deficits. Hypertensive encephalopathy is believed to be caused by acute failure of cerebrovascular autoregulation. Hypertensive emergency is treated with intravenous antihypertensive agents to reduce blood pressure by 25% within the first hour. Selective inhibition of cerebrovascular blood vessel permeability for the treatment of hypertensive emergency is beginning early clinical trials. © 2014 Elsevier B.V. All rights reserved.
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative syndrome, which is caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. CTE presents clinically as a composite syndrome of mood disorders and behavioral and cognitive impairment, with or without sensorimotor impairment. Symptoms of CTE may begin with persistent symptoms of acute traumatic brain injury (TBI) following a documented episode of brain trauma or after a latent period that may range from days to weeks to months and years, up to 40 years following a documented episode of brain trauma or cessation of repetitive TBI. Posttraumatic encephalopathy is distinct from CTE, can be comorbid with CTE, and is a clinicopathologic syndrome induced by focal and/or diffuse, gross and/or microscopic destruction of brain tissue following brain trauma. The brain of a CTE sufferer may appear grossly unremarkable, but shows microscopic evidence of primary and secondary proteinopathies. The primary proteinopathy of CTE is tauopathy, while secondary proteinopathies may include, but are not limited to, amyloidopathy and TDP proteinopathy. Reported prevalence rates of CTE in cohorts exposed to TBI ranges from 3 to 80% across age groups.
Amarnath, C; Helen Mary, T; Periakarupan, A; Gopinathan, K; Philson, J
Our objective is to study the MR imaging pattern in neonatal parechoviral leucoencephalitis, a rare cause of neonatal white matter abnormality and to differentiate it from hypoxic-ischemic encephalopathy which is the commonest cause of white matter change in neonates. We evaluated 25 neonates who presented with features of encephalopathy. Cranial ultrasound and MR imaging was done in all the cases. The pattern of white matter abnormality was analyzed in all cases. Neonatal leucoencephalitis caused by HPeV has a distinctive clinical presentation and has predilection for the white matter, causing diffusion restricting signal intensity changes involving the periventricular and subcortical white matter, in particular the frontal white matter, also the corpus callosum, internal capsule, external capsule and pyramidal tracts of the supratentorial brain and cerebral peduncle with relative sparing of occipital white matter, thalamus, basal ganglia and the infratentorial regions. Follow up imaging shows disappearance of the lesion without white matter loss. Whereas mild to moderate hypoxic-ischemic injury in a full-term neonate causes lesions in the watershed areas, and subcortical white matter predominantly involving the parietooccipital region and perirolandic region. Thalamus, brainstem, cerebellum, and deep gray matter structures are involved depending on the severity. White matter changes in the neonatal period are commonly associated with hypoxic-ischemic injuries and metabolic causes, less frequently, infection like parechovirus leucoencephalitis. HPeV infection must be considered in infants with specific pattern of white matter change but no convincing history of a perinatal hypoxic-ischemic insult, thus differentiating it from HIE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
McTague, Amy; Cross, J Helen
Epileptic encephalopathy is defined as a condition where the epileptic activity itself may contribute to the severe neurological and cognitive impairment seen, over and above that which would be expected from the underlying pathology alone. The epilepsy syndromes at high risk of this are a disparate group of conditions characterized by epileptic seizures that are difficult to treat and developmental delay. In this review, we discuss the ongoing debate regarding the significance of inter-ictal discharges and the impact of the seizures themselves on the cognitive delay or regression that is a common feature of these syndromes. The syndromes also differ in many ways and we provide a summary of the key features of the early-onset epileptic encephalopathies including Ohtahara and West syndromes in addition to later childhood-onset syndromes such as Lennox Gastaut and Doose syndromes. An understanding of the various severe epilepsy syndromes is vital to understanding the rationale for treatment. For example, the resolution of hypsarrhythmia in West syndrome is associated with an improvement in cognitive outcome and drives treatment choice, but the same cannot be applied to frequent inter-ictal discharges in Lennox Gastaut syndrome. We discuss the evidence base for treatment where it is available and describe current practice where it is not. For example, in West syndrome there is some evidence for preference of hormonal treatments over vigabatrin, although the choice and duration of hormonal treatment remains unclear. We describe the use of conventional and newer anti-epileptic medications in the various syndromes and discuss which medications should be avoided. Older possibly forgotten treatments such as sulthiame and potassium bromide also have a role in the severe epilepsies of childhood. We discuss hormonal treatment with particular focus on the treatment of West syndrome, continuous spike wave in slow wave sleep (CSWS)/electrical status epilepticus in slow wave
Morillas, Rosa M; Sala, Marga; Planas, Ramon
Hepatic encephalopathy (HE) is a frequent complication of cirrhosis which, in addition to producing a great social impact, deteriorates the quality of life of patients and is considered a sign of advanced liver disease and therefore a clinical indication for liver transplant evaluation. Patients who have had episodes of HE have a high risk of recurrence. Thus, after the HE episode resolves, it is recommended: control and prevention of precipitating factors (gastrointestinal bleeding, spontaneous bacterial peritonitis, use of diuretics with caution, avoid nervous system depressant medications), continued administration of non-absorbable disaccharides such as lactulose or lactitol, few or non-absorbable antibiotics such as rifaximin and assess the need for a liver transplant as the presence of a HE episode carries a poor prognosis in cirrhosis. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Ross, C. A.
Gasoline sniffing is endemic in northern Manitoba and perhaps throughout much of northern Canada. Its most serious complication is lead encephalopathy, which can be fatal. Most of the toxic effects are thought to be due to tetraethyl lead and its metabolites. The specific treatment is chelation therapy, for which a protocol has been developed at the Health Sciences Centre, Winnipeg. Lead encephalopathy, however, is a manifestation of social, cultural and psychologic malaise. PMID:7139470
Aatif, T; El Farouki, M R; Benyahia, M
Posterior reversible encephalopathy syndrome (PRES) is a clinical and neuroimaging entity characterized by headache, visual field deficits, changes in mentation and seizures, and by typical neuro-imaging features such as areas of sub-cortical edema, occasionally cortical, involving predominantly the occipital and parietal lobes of both hemispheres. Hypertension, uremia, immunosuppressive drugs neurotoxicity, preeclampsia or eclampsia, renal disease, and sepsis are the most common etiologies of PRES. Less common, it has been described in the setting of autoimmune disease. We report a case of PRES which was associated with hypertensive crisis in a patient with renal failure. Antihypertensive therapy and hemodialysis resulted in complete recovery.
Ohira, Junichiro; Mori, Nobuyuki; Kajikawa, Shunsuke; Nakamura, Takeshi; Arisato, Tetsuya; Takahashi, Makio
Posterior reversible encephalopathy syndrome (PRES) typically affects the posterior subcortical white matter. We report the case of a 55-year-old man with atypical PRES, who had malignant hypertension and renal dysfunction. Magnetic resonance imaging of the brain revealed extensive vasogenic edema in the deep white matter including the temporal pole, as well as in the brainstem and cerebellum. Antihypertensive therapy and hemodialysis contributed to both clinical and radiological improvement. Involvement of the deep white matter including the temporal pole, which is rarely affected in an ischemic stroke, should be recognized as a potential sign of PRES. PMID:27904123
Gleeson, J G; duPlessis, A J; Barnes, P D; Riviello, J J
Cyclosporin A is associated with an acute encephalopathy including seizures and alterations in mental status, herein referred to as cyclosporin A acute encephalopathy and seizure syndrome. The clinical history, electroencephalogram (EEG), and neuroimaging findings in 19 children with cyclosporin A acute encephalopathy and seizure syndrome over a 10-year period were reviewed in order to delineate clinical characteristics, imaging features, and to determine the risk of seizure recurrence in this population. All 19 had motor seizures associated with other features of cortical and subcortical dysfunction. The acute mean cyclosporin A level was 342 microg/L, but was within the "therapeutic" range in five cases. Brain imaging by computed tomography (CT) or magnetic resonance imaging (MRI) in the acute or subacute phase revealed lesions characteristic of cyclosporin A toxicity in 14 cases. Acute EEG abnormalities were present in all and included epileptiform discharges or focal slowing. Patients were followed for a median of 49 months (1-9 years). Follow-up imaging (n = 10) showed lesion resolution or improvement in the majority while EEG (n = 10) had normalized in only three. Seizures recurred in six patients and only in those with persistent EEG or imaging abnormalities. No patient had a second episode of cyclosporin A associated neurotoxicity or seizure. It appears that a significant risk of seizure recurrence exists following cyclosporin A acute encephalopathy and seizure syndrome and primarily in those children with persistent EEG or imaging abnormalities.
Levine, R L; Lagreze, H L; Dobkin, J A; Turski, P A
A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.
Villafruela, Javier; Crites, Sebastian; Cheng, Bastian; Knaack, Christian; Thomalla, Götz; Menon, Bijoy K.; Forkert, Nils D.
Stroke is a leading cause of death and disability in the western hemisphere. Acute ischemic strokes can be broadly classified based on the underlying cause into atherosclerotic strokes, cardioembolic strokes, small vessels disease, and stroke with other causes. The ability to determine the exact origin of an acute ischemic stroke is highly relevant for optimal treatment decision and preventing recurrent events. However, the differentiation of atherosclerotic and cardioembolic phenotypes can be especially challenging due to similar appearance and symptoms. The aim of this study was to develop and evaluate the feasibility of an image-based machine learning approach for discriminating between arteriosclerotic and cardioembolic acute ischemic strokes using 56 apparent diffusion coefficient (ADC) datasets from acute stroke patients. For this purpose, acute infarct lesions were semi-atomically segmented and 30,981 geometric and texture image features were extracted for each stroke volume. To improve the performance and accuracy, categorical Pearson's χ2 test was used to select the most informative features while removing redundant attributes. As a result, only 289 features were finally included for training of a deep multilayer feed-forward neural network without bootstrapping. The proposed method was evaluated using a leave-one-out cross validation scheme. The proposed classification method achieved an average area under receiver operator characteristic curve value of 0.93 and a classification accuracy of 94.64%. These first results suggest that the proposed image-based classification framework can support neurologists in clinical routine differentiating between atherosclerotic and cardioembolic phenotypes.
Cohen, Alexandra O.; Dreyfuss, Michael F. W.; Casey, B. J.
The capacity to suppress inappropriate thoughts, emotions and actions in favor of appropriate ones shows marked changes throughout childhood and adolescence. Most research has focused on pre-frontal circuit development to explain these changes. Yet, subcortical circuitry involving the amygdala and ventral striatum (VS) has been shown to modulate cue-triggered motivated behaviors in rodents. The nature of the interaction between these two subcortical regions in humans is less well understood, especially during development when there appears to be heightened sensitivity to emotional cues. In the current study, we tested how task-based cortico-subcortical and subcortico-subcortical functional connectivity in 155 participants ages from 5 to 32 impacted cognitive control performance on an emotional go/nogo task. Functional connectivity between the amygdala and VS was inversely correlated with age and predicted cognitive control to emotional cues, when controlling for performance to neutral cues. In contrast, increased medial pre-frontal-amygdala connectivity was associated with better cognitive control to emotional cues and this cortical-subcortical connectivity mediated the association between amygdala-VS connectivity and emotional cognitive control. These findings suggest a dissociation in how subcortical-subcortical and cortical-subcortical connectivity impact cognitive control across development. PMID:27445212
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein misfolding neurodegenerative diseases. TSEs have been described in several species including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, tr...
Yi, Juneyoung; Padalino, David J; Chin, Lawrence S; Montenegro, Philip; Cantu, Robert C
Sports-related concussion has gained increased prominence, in part due to media coverage of several well-known athletes who have died from consequences of chronic traumatic encephalopathy (CTE). CTE was first described by Martland in 1928 as a syndrome seen in boxers who had experienced significant head trauma from repeated blows. The classic symptoms of impaired cognition, mood, behavior, and motor skills also have been reported in professional football players, and in 2005, the histopathological findings of CTE were first reported in a former National Football League (NFL) player. These finding were similar to Alzheimer's disease in some ways but differed in critical areas such as a predominance of tau protein deposition over amyloid. The pathophysiology is still unknown but involves a history of repeated concussive and subconcussive blows and then a lag period before CTE symptoms become evident. The involvement of excitotoxic amino acids and abnormal microglial activation remain speculative. Early identification and prevention of this disease by reducing repeated blows to the head has become a critical focus of current research.
Maddison, J E
The case records of 21 dogs with congenital portosystemic encephalopathy are reviewed. The disorder was most common in Australian cattledogs (blue heelers; 8 cases), Old English sheepdogs (3 cases) and Maltese terriers (3 cases). Extra-hepatic shunts occurred in small breeds, with the exception of 1 cattledog, while intra-hepatic shunts occurred in the medium to large breeds. The most common clinical pathology abnormalities were abnormal ammonia tolerance, mild to moderate increases in plasma alanine aminotransferase or alkaline phosphatase concentrations, decreased total serum protein concentrations, increased fasting ammonia concentrations and ammonium biurate crystalluria. Radiological examination revealed that all the dogs had a small liver. The kidneys were enlarged in 5 of 10 dogs in which kidney size could be estimated. Surgical ligation of an extra-hepatic shunt was successful in 2 of 4 dogs in which it was attempted. Medical management resulted in alleviation of clinical signs in 5 of 8 dogs. The period of successful treatment ranged from a few months to over a year.
Kimberlin, R H
Scrapie in sheep and goats is the best known of the transmissible encephalopathies of animals. The combination of maternal transmission of infection and long incubation periods effectively maintains the infection in flocks. A single sheep gene (Sip) controls both experimental and natural scrapie and the discovery of allelic markers could enable the use of sire selection in the control of the natural disease. Studies of experimental rodent scrapie show that neuroinvasion occurs by spread of infection from visceral lymphoreticular tissues along nerve fibers to mid-thoracic cord. The slowness of scrapie is due to restrictions on replication and cell-to-cell spread of infection affecting neuroinvasion and subsequent neuropathogenesis. Probably both stages in mice are controlled by Sinc gene, the murine equivalent of Sip. The glycoprotein PrP may be the normal product of Sinc gene. Posttranslationally modified PrP forms the disease specific "scrapie associated fibrils" and may also be a constituent of the infectious agent. Scrapie-like diseases have been reported in mink and several species of ruminants including cattle. All of them may be caused by the recycling of scrapie infected sheep material in animal feed. The human health implications are discussed. PMID:2407328
Gofton, Teneille E; Young, G Bryan
Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs secondary to infection in the body without overt CNS infection. SAE is frequently encountered in critically ill patients in intensive care units, and in up to 70% of patients with severe systemic infection. The severity of SAE can range from mild delirium to deep coma. Seizures and myoclonus are infrequent and cranial nerves are almost always spared, but most severe cases have an associated critical illness neuromyopathy. Development of SAE probably involves a number of mechanisms that are not mutually exclusive and vary from patient to patient. Substantial neurological and psychological morbidities often occur in survivors. Mortality is almost always due to multiorgan failure rather than neurological complications, and is almost 70% in patients with severe SAE. Further research into the pathophysiology, management and prevention of SAE is needed. This Review discusses the epidemiology and clinical presentation of SAE. Recent evidence for SAE pathophysiology is outlined and a diagnostic approach to patients with this syndrome is presented. Lastly, prognosis and management of SAE is discussed.
Chaudhry, Neera; Duggal, Ashish Kumar
Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis.
Cotena, Simona; Piazza, Ornella
Sepsis-associated encephalopathy (SAE) is defined as a diffuse or multifocal cerebral dysfunction induced by the systemic response to the infection without clinical or laboratory evidence of direct brain infection. Its pathogenesis is multifactorial. SAE generally occurs early during severe sepsis and precedes multiple-organ failure. The most common clinical feature of SAE is the consciousness alteration which ranges from mildly reduced awareness to unresponsiveness and coma. Diagnosis of SAE is primarily clinical and depends on the exclusion of other possible causes of brain deterioration. Electroencephalography (EEG) is almost sensitive, but it is not specific for SAE. Computed Tomography (CT) head scan generally is negative in case of SAE, while Magnetic Resonance Imaging (MRI) can show brain abnormalities in case of SAE, but they are not specific for this condition. Somatosensitive Evoked Potentials (SEPs) are sensitive markers of developing cerebral dysfunction in sepsis. Cerebrospinal fluid (CBF) analysis is generally normal, a part an inconstant elevation of proteins concentration. S100B and NSE have been proposed like biomarkers for diagnosis of SAE, but the existing data are controversial. SAE is reversible even if survivors of severe sepsis have often long lasting or irreversible cognitive and behavioral sequel; however the presence of SAE can have a negative influence on survival. A specific therapy of SAE does not exist and the outcome depends on a prompt and appropriate treatment of sepsis as whole.
Chaudhry, Neera; Duggal, Ashish Kumar
Sepsis associated encephalopathy (SAE) is a common but poorly understood neurological complication of sepsis. It is characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection. The pathophysiology of SAE is complex and multifactorial including a number of intertwined mechanisms such as vascular damage, endothelial activation, breakdown of the blood brain barrier, altered brain signaling, brain inflammation, and apoptosis. Clinical presentation of SAE may range from mild symptoms such as malaise and concentration deficits to deep coma. The evaluation of cognitive dysfunction is made difficult by the absence of any specific investigations or biomarkers and the common use of sedation in critically ill patients. SAE thus remains diagnosis of exclusion which can only be made after ruling out other causes of altered mentation in a febrile, critically ill patient by appropriate investigations. In spite of high mortality rate, management of SAE is limited to treatment of the underlying infection and symptomatic treatment for delirium and seizures. It is important to be aware of this condition because SAE may present in early stages of sepsis, even before the diagnostic criteria for sepsis can be met. This review discusses the diagnostic approach to patients with SAE along with its epidemiology, pathophysiology, clinical presentation, and differential diagnosis. PMID:26556425
Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo
Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae. Georg Thieme Verlag KG Stuttgart · New York.
Yamamoto, Akira; Hayakawa, Katsumi; Houjyou, Makoto
We present the MRI and CT findings of one child with cyclosporine-related encephalopathy, and one child with hypertensive encephalopathy following cyclosporine-related encephalopathy. The imaging findings were shown well on T2-weighted and fluid-attenuated inversion recovery (FLAIR) MR images. Cyclosporine-related encephalopathy was distributed predominantly in the posterior white matter. Hypertensive encephalopathy showed similar changes of CT attenuation, but with wider distribution. These two disorders seem to have the same pathogenesis.
Green, Rebecca; Scott, L Keith; Minagar, Alireza; Conrad, Steven
Sepsis associated encephalopathy (SAE) is a poorly understood condition that is associated with severe sepsis and appears to have a negative influence on survival. The incidence of encephalopathy secondary to sepsis is unknown. Amino acid derangements, blood-brain barrier disruption, abnormal neurotransmitters, and direct CNS effect are possible causes of septic encephalopathy. Research has not defined the pathogenesis of SAE.
Kawadler, Jamie M; Clayden, Jonathan D; Kirkham, Fenella J; Cox, Timothy C; Saunders, Dawn E; Clark, Chris A
Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls, SCA with SCI (n = 13) and SCA without visible abnormality (n = 13). Specific volumetric differences were found in the hippocampus, amygdala, pallidum, caudate, putamen, thalamus, and cerebellum. This is the first study to demonstrate subcortical volume change in SCA, with the most severe volumetric deficits occurring in children with SCI seen on MRI.
Araújo, Sheila Espírito Santo; Mendonça, Henrique Rocha; Wheeler, Natalie A; Campello-Costa, Paula; Jacobs, Kimberle M; Gomes, Flávia C A; Fox, Michael A; Fuss, Babette
Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail. Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS. Demyelination and inflammation were assessed by real-time polymerase chain reaction and immunohistochemistry. Synaptic changes associated with inflammatory demyelination in the dorsal lateral geniculate nucleus (dLGN) were determined by immunohistochemistry, Western blot analysis, and electrophysiological field potential recordings. In the cuprizone model, demyelination was observed in retinorecipient regions of the subcortical visual system, in particular the dLGN, where it was found accompanied by microglia activation and astrogliosis. In contrast, anterior parts of the pathway, i.e., the optic nerve and tract, appeared largely unaffected. Under the inflammatory demyelinating conditions, as seen in the dLGN of cuprizone-treated mice, there was an overall decrease in excitatory synaptic inputs from retinal ganglion cells. At the same time, the number of synaptic complexes arising from gamma-aminobutyric acid (GABA)-generating inhibitory neurons was found increased, as were the synapses that contain the N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B and converge onto inhibitory neurons. These synaptic changes were functionally found associated with a shift toward an overall increase in network inhibition. Using the cuprizone model of inflammatory demyelination, our data reveal a novel form of synaptic (mal)adaption in the CNS that is characterized by a shift of the excitation/inhibition balance toward inhibitory
Kornacka, Maria K; Bokiniec, Renata; Bargiel, Agata
Encephalopathy in a common neonatological sense is a term referring to a complex of clinical symptoms occurring in term infants in the first days of their life as a result of hypoxic-ischemic lesions. However, if we accept the encyclopedic definition of encephalopathy as a vast or multifocal brain lesions caused by a variety of factors, we may use the term to describe all patients with traumatic, hypoxic or toxic brain lesions, and therefore also newborns at different levels of maturity. Contrary to term newborns, in which case the hypoxic-ischemic encephalopathy are mostly intrauterine, for preterm infants there is a number of factors which destroy neural tissue postnatally The occurrence of those factors is often influenced by elements of essential intensive care. The article describes the most common biochemical disturbances and clinical causes.
Kaplan, Peter W; Sutter, Raoul
There is an increasing recognition of autoimmune limbic encephalopathy with the hope for earlier diagnosis and expedited and improved treatment. Although antibody testing remains the definitive clinical diagnostic feature, the presentation of a rapid dementia, behavioral changes, and seizures leads to investigation using cerebral imaging, electroencephalography, and cerebrospinal fluid to confirm the diagnosis and also to exclude similar disorders. The electroencephalographer may be asked to comment on the types of electroencephalography abnormality and provide input toward the diagnosis of limbic encephalopathy. This article reviews the literature on limbic paraneoplastic and nonparaneoplastic encephalopathies, providing descriptions and examples of the electroencephalography findings. Typically, there are patterns of slow theta and delta activity and different patterns of temporal and frontal epileptic activity.
Lemmon, Monica E; Donohue, Pamela K; Parkinson, Charlamaine; Northington, Frances J; Boss, Renee D
We aimed to characterize the parent experience of caring for an infant with neonatal encephalopathy. In this mixed-methods study, we performed semistructured interviews with parents whose infants were enrolled in an existing longitudinal cohort study of therapeutic hypothermia between 2011 and 2014. Thematic saturation was achieved after 20 interviews. Parent experience of caring for a child with neonatal encephalopathy was characterized by 3 principal themes. Theme 1: Many families described cumulative loss and grief throughout the perinatal crisis, critical neonatal course, and subsequent missed developmental milestones. Theme 2: Families experienced entangled infant and broader family interests. Theme 3: Parents evolved into and found meaning in their role as an advocate. These data offer insight into the lived experience of parenting an infant with neonatal encephalopathy. Primary data from parents can serve as a useful framework to guide the development and interpretation of parent-centered outcomes.
Danti, Federica Rachele; Galosi, Serena; Romani, Marta; Montomoli, Martino; Carss, Keren J.; Raymond, F. Lucy; Parrini, Elena; Bianchini, Claudia; McShane, Tony; Dale, Russell C.; Mohammad, Shekeeb S.; Shah, Ubaid; Mahant, Neil; Ng, Joanne; McTague, Amy; Samanta, Rajib; Vadlamani, Gayatri; Valente, Enza Maria; Leuzzi, Vincenzo; Kurian, Manju A.
Objective: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. Methods: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. Results: Patients first presented in early childhood (median age of presentation 10 months, range 0–48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. Conclusions: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia. PMID:28357411
Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S
West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? © 2017 Elsevier Inc. All rights reserved.
Wexler, B C
Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function.
Wexler, B. C.
Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function. Images Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 PMID:1008997
Dawson, Caitlin; Aalto, Daniel; Šimko, Juraj; Putkinen, Vesa; Tervaniemi, Mari; Vainio, Martti
The complex auditory brainstem response (cABR) can reflect language-based plasticity in subcortical stages of auditory processing. It is sensitive to differences between language groups as well as stimulus properties, e.g. intensity or frequency. It is also sensitive to the synchronicity of the neural population stimulated by sound, which results in increased amplitude of wave V. Finnish is a full-fledged quantity language, in which word meaning is dependent upon duration of the vowels and consonants. Previous studies have shown that Finnish speakers have enhanced behavioural sound duration discrimination ability and larger cortical mismatch negativity (MMN) to duration change compared to German and French speakers. The next step is to find out whether these enhanced duration discrimination abilities of quantity language speakers originate at the brainstem level. Since German has a complementary quantity contrast which restricts the possible patterns of short and long vowels and consonants, the current experiment compared cABR between nonmusician Finnish and German native speakers using seven short complex stimuli. Finnish speakers had a larger cABR peak amplitude than German speakers, while the peak onset latency was only affected by stimulus intensity and spectral band. The results suggest that early cABR responses are better synchronised for Finns, which could underpin the enhanced duration sensitivity of quantity language speakers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Johnson, Curtis L; Schwarb, Hillary; D J McGarry, Matthew; Anderson, Aaron T; Huesmann, Graham R; Sutton, Bradley P; Cohen, Neal J
Viscoelastic mechanical properties of the brain assessed with magnetic resonance elastography (MRE) are sensitive measures of microstructural tissue health in neurodegenerative conditions. Recent efforts have targeted measurements localized to specific neuroanatomical regions differentially affected in disease. In this work, we present a method for measuring the viscoelasticity in subcortical gray matter (SGM) structures, including the amygdala, hippocampus, caudate, putamen, pallidum, and thalamus. The method is based on incorporating high spatial resolution MRE imaging (1.6 mm isotropic voxels) with a mechanical inversion scheme designed to improve local measures in pre-defined regions (soft prior regularization [SPR]). We find that in 21 healthy, young volunteers SGM structures differ from each other in viscoelasticity, quantified as the shear stiffness and damping ratio, but also differ from the global viscoelasticity of the cerebrum. Through repeated examinations on a single volunteer, we estimate the uncertainty to be between 3 and 7% for each SGM measure. Furthermore, we demonstrate that the use of specific methodological considerations-higher spatial resolution and SPR-both decrease uncertainty and increase sensitivity of the SGM measures. The proposed method allows for reliable MRE measures of SGM viscoelasticity for future studies of neurodegenerative conditions. Hum Brain Mapp 37:4221-4233, 2016. © 2016 Wiley Periodicals, Inc.
Drake-Pérez, Marta; Marco de Lucas, Enrique; Lyo, John; Fernández-Torre, José L
To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). We reviewed all cases reported previously, as well as 4 patients diagnosed in our center. We included a total of 8 patients. All subjects had clinical and EEG findings compatible with SESA syndrome and at least one MRI study that did not show other underlying condition that could be responsible for the clinical presentation. Initial MRI studies revealed the following features: cortical-subcortical areas of increased T2/FLAIR signal and restricted diffusion (6 patients), hyperperfusion (3 patients), atrophy (5 patients), chronic microvascular ischemic changes (4 patients). Follow-up MRI was performed in half of the patients, all showing a resolution of the hyperintense lesions, but developing focal atrophic changes in 75%. SESA syndrome should be included among the alcohol-related encephalopathies. Its radiological features include transient cortical-subcortical T2-hyperintense areas with restricted diffusion (overlapping the typical findings in status epilepticus) observed in a patient with atrophy and chronic multifocal vascular lesions. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Moerel, Michelle; De Martino, Federico; Uğurbil, Kâmil; Yacoub, Essa; Formisano, Elia
To date it remains largely unknown how fundamental aspects of natural sounds, such as their spectral content and location in space, are processed in human subcortical structures. Here we exploited the high sensitivity and specificity of high field fMRI (7 Tesla) to examine the human inferior colliculus (IC) and medial geniculate body (MGB). Subcortical responses to natural sounds were well explained by an encoding model of sound processing that represented frequency and location jointly. Frequency tuning was organized in one tonotopic gradient in the IC, whereas two tonotopic maps characterized the MGB reflecting two MGB subdivisions. In contrast, no topographic pattern of preferred location was detected, beyond an overall preference for peripheral (as opposed to central) and contralateral locations. Our findings suggest the functional organization of frequency and location processing in human subcortical auditory structures, and pave the way for studying the subcortical to cortical interaction required to create coherent auditory percepts. PMID:26597173
Gattringer, Thomas; Eppinger, Sebastian; Pinter, Daniela; Pirpamer, Lukas; Berghold, Andrea; Wünsch, Gerit; Ropele, Stefan; Wardlaw, Joanna M; Enzinger, Christian; Fazekas, Franz
New imaging criteria for recent small subcortical infarcts have recently been proposed, replacing the earlier term 'lacunar infarction', but their applicability and impact on lesion selection is yet unknown. To collect information on the morphologic characteristics and variability of recent small subcortical infarcts on magnetic resonance imaging in regard to lesion location and demographic variables. We identified all patients with acute stroke and cerebral magnetic resonance imaging from 2008 to 2013 in our hospital database and selected those with a single recent small subcortical infarct defined by an estimated maximal axial diameter of 20 mm. Recent small subcortical infarcts were segmented on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence to calculate the largest axial and longitudinal diameter and lesion volume. We assessed morphometric differences of recent small subcortical infarcts regarding location and demographic variables and the impact of different recent small subcortical infarct definitions on lesion selection. Three hundred forty-four patients (median age 72; range 25-92 years, 65% male) were selected. Most recent small subcortical infarcts were located in the basal ganglia (n = 111), followed by pons (n = 92), thalamus (n = 77), and centrum semiovale (n = 64). Quantitative measurements confirmed visual assessment of the axial diameter in 95%. All morphometric variables were strongly intercorrelated and comparable on diffusion-weighted imaging and fluid-attenuated inversion recovery sequence. Recent small subcortical infarcts in the basal ganglia were significantly larger both in the axial and longitudinal direction compared with other regions. Dichotomization of recent small subcortical infarcts according to axial (≤ / >15 mm) or longitudinal (≤ / >20 mm) sizes resulted in different regional frequencies and distributions. Age, gender, and time from stroke onset to magnetic resonance imaging
Schneider, J P; Krohmer, S; Günther, A; Zimmer, C
In the nine years since the posterior reversible (leuc) encephalopathy syndrome (PRES) was first described, a number of causes have been under discussion. These not only include arterial hypertension, i. e. hypertensive crises, but also various toxic substances, i. e. immunosuppressive or chemotherapeutic agents, that are responsible for the formation of the symptoms and characteristic MR tomographic brain findings. Initial and follow-up MRI examinations of 8 patients were analyzed. All patients had acute neurological symptoms (headaches, seizures, visual disorders and vigilance disturbances) together with a detectable hypertensive crisis. MRI disclosed increased signal intensity in subcortical and some cortical lesions in all patient FLAIR sequences. These changes were particularly extensive in the posterior circulation (occipital, cerebellum and brain stem) although they were also detected in brain areas supplied by the carotid artery. However, a cytotoxic genesis of the changes was ruled out in each patient by means of a normal DWI. Furthermore, when the blood pressure was normalized, reversibility of the lesions as proof of the diagnosis was detectable. The imaging findings can be typically analyzed as a predominantly posterior distribution of encephalopathic lesions with a high probability of reversibility after lowering blood pressure was patients suffering from a critical increase in blood pressure with corresponding neurological symptoms. The exact pathophysiology remains unclear, but the cause currently most favored is a vasculopathy of the posterior circulation due to diminished adrenergic autoregulation in combination with a dysfunction of the endothelial cells. In conclusion, we suggest designating this subpopulation from the non-uniform pool of patients with posterior (leuc) encephalopathy as "hypertensive encephalopathy". "Hypertensive encephalopathy" has to be distinguished from "toxic encephalopathy", particularly due to different therapeutic and
Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J
Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.
Wade, Benjamin S. C.; Valcour, Victor; Busovaca, Edgar; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Wang, Yalin; Thompson, Paul M.
Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures' surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.
Tang, Yi; Xing, Yi; Lin, Michael T; Zhang, Jin; Jia, Jianping
Hashimoto's encephalopathy is a poorly understood syndrome consisting of heterogeneous neurological symptoms and high serum antithyroid antibody titers, typically responding to steroids. More clinical series studies are required to characterize the clinical, laboratory and imaging features, and outcomes, especially in the Chinese population. We analyzed the clinical, laboratory, and imaging features and outcomes of thirteen consecutive patients with Hashimoto's encephalopathy diagnosed in Xuan Wu Hospital, Beijing from 2005 to 2010 retrospectively. Cognitive impairment (84.6%) and psychiatric symptoms (38.5%) were the most frequent symptoms. Seizures (30.8%) and myoclonus (7.7%) were less common than previously described. Three (23.1%) patients showed abnormal signals in hippocampus or temporal lobe, which were believed related to their memory disorders or seizures. MRI changes showed resolution paralleling clinical improvement in one patient. Among eight patients who received steroid therapy, five patients recovered, one patient improved with residual deficits, and two patients relapsed or had no effect. Among five non-steroid treated patients, three patients experienced stable remission with antiepileptic drugs or general neurotrophic therapy, and two patients experienced continuous deterioration. Most patients with Hashimoto's encephalopathy showed good response to steroids. Some patients improved without steroid therapy. Considering its reversible course, we recommend that Hashimoto's encephalopathy should always be in the differential diagnosis while evaluating disorders of the central nervous system.
Chin, Juhee; Seo, Sang Won; Kim, Sook Hui; Park, Aram; Ahn, Hyun-Jung; Lee, Byung Hwa; Kang, Sue J; Na, Duk L
Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease.
Hibar, D P; Westlye, L T; van Erp, T G M; Rasmussen, J; Leonardo, C D; Faskowitz, J; Haukvik, U K; Hartberg, C B; Doan, N T; Agartz, I; Dale, A M; Gruber, O; Krämer, B; Trost, S; Liberg, B; Abé, C; Ekman, C J; Ingvar, M; Landén, M; Fears, S C; Freimer, N B; Bearden, C E; Sprooten, E; Glahn, D C; Pearlson, G D; Emsell, L; Kenney, J; Scanlon, C; McDonald, C; Cannon, D M; Almeida, J; Versace, A; Caseras, X; Lawrence, N S; Phillips, M L; Dima, D; Delvecchio, G; Frangou, S; Satterthwaite, T D; Wolf, D; Houenou, J; Henry, C; Malt, U F; Bøen, E; Elvsåshagen, T; Young, A H; Lloyd, A J; Goodwin, G M; Mackay, C E; Bourne, C; Bilderbeck, A; Abramovic, L; Boks, M P; van Haren, N E M; Ophoff, R A; Kahn, R S; Bauer, M; Pfennig, A; Alda, M; Hajek, T; Mwangi, B; Soares, J C; Nickson, T; Dimitrova, R; Sussmann, J E; Hagenaars, S; Whalley, H C; McIntosh, A M; Thompson, P M; Andreassen, O A
Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. PMID:26857596
Hibar, D P; Westlye, L T; van Erp, T G M; Rasmussen, J; Leonardo, C D; Faskowitz, J; Haukvik, U K; Hartberg, C B; Doan, N T; Agartz, I; Dale, A M; Gruber, O; Krämer, B; Trost, S; Liberg, B; Abé, C; Ekman, C J; Ingvar, M; Landén, M; Fears, S C; Freimer, N B; Bearden, C E; Sprooten, E; Glahn, D C; Pearlson, G D; Emsell, L; Kenney, J; Scanlon, C; McDonald, C; Cannon, D M; Almeida, J; Versace, A; Caseras, X; Lawrence, N S; Phillips, M L; Dima, D; Delvecchio, G; Frangou, S; Satterthwaite, T D; Wolf, D; Houenou, J; Henry, C; Malt, U F; Bøen, E; Elvsåshagen, T; Young, A H; Lloyd, A J; Goodwin, G M; Mackay, C E; Bourne, C; Bilderbeck, A; Abramovic, L; Boks, M P; van Haren, N E M; Ophoff, R A; Kahn, R S; Bauer, M; Pfennig, A; Alda, M; Hajek, T; Mwangi, B; Soares, J C; Nickson, T; Dimitrova, R; Sussmann, J E; Hagenaars, S; Whalley, H C; McIntosh, A M; Thompson, P M; Andreassen, O A
Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
Striano, Pasquale; Striano, Salvatore; Tortora, Fabio; De Robertis, Edoardo; Palumbo, Daniela; Elefante, Andrea; Servillo, Giuseppe
Posterior Reversible Encephalopathy (PRES) is characterized by acute-onset headache, altered mental status, cortical blindness and seizures, with parietal-occipital involvement. We report all cases of PRES diagnosed in our intensive care unit during the last 4 years, and evaluate their outcome in terms of the different medical treatments used. Even if usually reversible, PRES can sometimes result in death or irreversible neurological deficit, such as chronic epilepsy. From January 2001 to January 2005, we identified 8 female patients with PRES. All patients underwent basal and follow-up brain MRI. Patients referred to Epilepsy Center (about 3000 patients) were reviewed in order to identify subjects with a clinical history of PRES. These latter were clinically re-evaluated and underwent video-EEG, MRI study and neuropsychological testing. Of the 8 patients, 5 had hypertensive encephalopathy during pregnancy; 2 had eclampsia during the postpartum period; 1 patient with chronic renal failure developed symptoms after immunosuppressive treatment. In all patients but 1, neurological and radiological abnormalities resolved after appropriate treatment. In addition, we found 2 patients with temporal lobe epilepsy subsequent to a previous PRES. MRI revealed cortical-subcortical malacia in the parietal-occipital regions. The widespread use of MRI technology has made PRES familiar to many clinicians. Although PRES is reversible when treatment is instituted, delayed diagnosis and therapy can result in chronic neurological sequelae. The relationship between hypertensive encephalopathy and chronic epilepsy needs to be confirmed by longitudinal studies. Normalization of blood pressure and treatment of seizures deserves particular attention.
Ishikura, Kenji; Ikeda, Masahiro; Hamasaki, Yuko; Hataya, Hiroshi; Shishido, Seiichirou; Asanuma, Hiroshi; Nishimura, Gen; Hiramoto, Ryugo; Honda, Masataka
Posterior reversible encephalopathy syndrome is a distinctive clinicoradiological entity observed in a variety of clinical settings, including pediatric patients. A greater prevalence of this syndrome has been suggested in kidney transplant recipients and patients with kidney disease. Although usually considered benign and reversible, characteristics of this syndrome in pediatric patients remain obscure. The objective of the present study involved disclosing details of imaging findings, as well as the clinical course and prevalence of the syndrome in this field. We investigated kidney transplant recipients and pediatric patients with kidney disease in our institution from 1990 to 2004. For these patients, clinical course, imaging findings, blood pressure, concurrent medical illnesses, and administrative condition of calcineurin inhibitors were analyzed. Twenty cases of posterior reversible encephalopathy syndrome were investigated in patients ranging in age from 1.9 to 18.3 years. In most patients, radiological abnormalities extended to the gray matter (17 of 20 patients), frontal and temporal lobes, and even the cerebellum (16 patients). Of 177 kidney transplant recipients (cyclosporine, 127 patients; tacrolimus, 50 patients), 6 patients administered cyclosporine (4.7%) and 4 patients administered tacrolimus (8.0%) developed the syndrome after transplantation. Posterior reversible encephalopathy syndrome should be suspected in pediatric kidney transplant recipients and patients with kidney disease if they have a sudden episode of neurological symptoms, even if imaging findings are not restricted to the subcortical white matter of the occipital region.
Magno Pereira, Vítor; Marote Correia, Luís; Rodrigues, Tiago; Serrão Faria, Gorete
The posterior reversible encephalopathy syndrome is a neurological syndrome characterized by headache, confusion, visual disturbances and seizures associated with identifiable areas of cerebral edema on imaging studies. The authors report the case of a man, 33 years-old, leukodermic with a history of chronic alcohol and tobacco consumption, who is admitted to the emergency department for epigastric pain radiating to the back and vomiting with about six hours of evolution and an intense holocranial headache for two hours. His physical examination was remarkable for a blood pressure of 190/100 mmHg and tenderness in epigastrium. His analytical results revealed emphasis on amylase 193 U/L and lipase 934 U/L. During the observation in the emergency department,he presented a generalized tonic-clonic seizure. Abdominal ultrasonography was performed and suggestive of pancreatitis withoutgallstones signals. Head computed tomography showed subarachnoid haemorrhage and a small right frontal cortical haemorrhage. The brain magnetic resonance imaging done one week after admission showed areas of a bilateral and symmetrical T2 / FLAIR hyperintensities in the subcortical white matter of the parietal and superior frontal regions, suggesting a diagnosis of posterior reversible encephalopathy syndrome. Abdominal computed tomography (10 days after admission) demonstrated a thickened pancreas in connection with inflammation and two small hypodense foci in the anterior part of the pancreas body, translating small foci of necrosis. The investigation of a thrombophilic defect revealed a heterozygous G20210A prothrombin gene mutation. The patient was discharged without neurological sequelae and asymptomatic. The follow-up brain magnetic resonance imaging confirmed the reversal of the lesions, confirming the diagnosis.
Sterling, Nicholas W; Du, Guangwei; Lewis, Mechelle M; Swavely, Steven; Kong, Lan; Styner, Martin; Huang, Xuemei
Cortical atrophy has been documented in both Parkinson's disease (PD) and healthy aging, but its relationship to changes in subcortical white matter is unknown. This was investigated by obtaining T1- and diffusion-weighted images from 76 PD and 70 controls at baseline and 18 and 36 months, from which cortical volumes and underlying subcortical white matter axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) were determined. Twelve of 69 cortical subregions had significant group differences, and for these, underlying subcortical white matter was explored. At baseline, higher cortical volumes were significantly correlated with lower underlying subcortical white matter AD, RD, and higher FA (ps ≤ 0.017) in PD. Longitudinally, higher rates of cortical atrophy in PD were associated with increased rates of change in AD RD, and FA values (ps ≤ 0.0013) in 2 subregions explored. The significant gray-white matter associations were not found in controls. Thus, unlike healthy aging, cortical atrophy and subcortical white matter changes may not be independent events in PD.
Ortega, Francisco B; Campos, Daniel; Cadenas-Sanchez, Cristina; Altmäe, Signe; Martínez-Zaldívar, Cristina; Martín-Matillas, Miguel; Catena, Andrés; Campoy, Cristina
A few studies have recently reported that higher cardiorespiratory fitness is associated with higher volumes of subcortical brain structures in children. It is, however, unknown how different fitness measures relate to shapes of subcortical brain nuclei. We aimed to examine the association of the main health-related physical fitness components with shapes of subcortical brain structures in a sample of forty-four Spanish children aged 9·7 (sd 0·2) years from the NUtraceuticals for a HEALthier life project. Cardiorespiratory fitness, muscular strength and speed agility were assessed using valid and reliable tests (ALPHA-fitness test battery). Shape of the subcortical brain structures was assessed by MRI, and its relationship with fitness was examined after controlling for a set of potential confounders using a partial correlation permutation approach. Our results showed that all physical fitness components studied were significantly related to the shapes of subcortical brain nuclei. These associations were both positive and negative, indicating that a higher level of fitness in childhood is related to both expansions and contractions in certain regions of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. Cardiorespiratory fitness was mainly associated with expansions, whereas handgrip was mostly associated with contractions in the structures studied. Future randomised-controlled trials will confirm or contrast our findings, demonstrating whether changes in fitness modify the shapes of brain structures and the extent to which those changes influence cognitive function.
Enatsu, Rei; Kanno, Aya; Ohtaki, Shunya; Akiyama, Yukinori; Ochi, Satoko; Mikuni, Nobuhiro
During brain surgery, there are difficulties associated with identifying subcortical fibers with no clear landmarks. We evaluated the usefulness of cortical evoked potentials with subcortical stimuli (subcortico-cortical evoked potential [SCEP]) in identifying subcortical fibers intraoperatively. We used SCEP to identify the pyramidal tract in 4 patients, arcuate fasciculus in 1 patient, and both in 2 patients during surgical procedures. After resection, a 1 × 4-electrode plate was placed on the floor of the removal cavity and 1-Hz alternating electrical stimuli were delivered to this electrode. A 4 × 5 recording electrode plate was placed on the central cortical areas to map the pyramidal tract and temporoparietal cortical areas for the arcuate fasciculus. SCEPs were obtained by averaging electrocorticograms time locked to the stimulus onset. The subcortical stimulation within 15 mm of the target fiber induced cortical evoked potentials in the corresponding areas, whereas the stimulation apart from 20 mm did not. Five patients showed transient worsening of neurologic symptoms after surgery. However, all patients recovered. SCEP was useful for identifying subcortical fibers and confirmed the preservation of these fibers. This technique is expected to contribute to the effectiveness and safety of resective surgery in patients with lesions close to eloquent areas. Copyright © 2016 Elsevier Inc. All rights reserved.
The term "hepatic encephalopathy" (HE) covers the neuropsychiatric syndrome associated with acute, chronic and acute-on-chronic liver disease (CLD). This paper deals with clinical features and diagnosis of HE in patients with liver cirrhosis and portal hypertension or porto-systemic shunts. The possible impact of concomitant disorders and the cirrhosis underlying liver disease upon brain function is described emphasizing the need of a detailed diagnostic work up of every individual case before diagnosing HE. Currently used methods for diagnosing minimal or covert hepatic encephalopathy are compared with regard to their sensitivity and specificity for diagnosing HE against the background of a multitude of concomitant disorders and diseases that could contribute to brain dysfunction.
Sanjay, K Mandal; Partha, P Chakraborty
The posterior/potentially reversible encephalopathy syndrome is a unique syndrome encountered commonly in hypertensive encephalopathy. A 13-year-old boy presented with of intermittent high grade fever, throbbing headache and non-projective vomiting for 5 days. The patient had a blood pressure of 120/80 mmHg but fundoscopy documented grade 3 hypertensive retinopathy. The patient improved symptomatically following conservative management. However, on the 5(th) post-admission day headache reappeared, and blood pressure measured at that time was 240/120 mmHg. Neuroimaging suggested white matter abnormalities. Search for the etiology of secondary hypertension led to the diagnosis of pheochromocytoma. Repeated MRI after successful surgical excision of the tumor patient showed reversal of white matter abnormalities. Reversible leucoencephalopathy due to pheochromocytoma have not been documented in literature previously.
Soós, Zsuzsanna; Salamon, Mónika; Oláh, Roland; Czégeni, Anna; Salamon, Ferenc; Folyovich, András; Winkler, Gábor
Wernicke encephalopathy (or Wernicke-Korsakoff encephalopathy) is a rarely diagnosed neurological disorder, which is caused by vitamin B1 deficiency. In the classical form it is characterized by a typical triad (confusion, oculomotor disturbance and ataxia), however, in the majority of the cases only confusion is present. It can be frequently observed in subjects with chronic alcohol consumption, but it may accompany different pathological states of which end stage malignant diseases are the most importants, where confusion may have different backgrounds. The authors present the case of an old male patient with advanced gastric cancer recognised and treated vitamin B1 deficiency, and they draw attention to difficulties of the diagnosis of Wernicke's disease.
Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul
Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521
Kantor, Sandeep; Prakash, Sadanandan; Chandwani, Juhi; Gokhale, Antara; Sarma, Kalpana; Albahrani, Maher J.
Wernicke's encephalopathy (WE) is a potentially reversible yet serious neurological manifestation caused by vitamin B1(thiamine) deficiency. It is commonly associated with heavy alcohol consumption. Other clinical associations are with hyperemesis gravidarum (HG), starvation, and prolonged intravenous feeding. Most patients present with the triad of ocular signs, ataxia, and confusion. It can be associated with life-threatening complication like central pontine myelinolysis (CPM). We report two cases of WE following HG, with two different outcomes. PMID:24701066
Sima, Anders A F
Diabetic encephalopathies are now accepted complications of diabetes. They appear to differ in type 1 and type 2 diabetes as to underlying mechanisms and the nature of resulting cognitive deficits. The increased incidence of Alzheimer's disease in type 2 diabetes is associated with insulin resistance, hyperinsulinemia and hyperglycemia, and commonly accompanying attributes such as hypercholesterolemia, hypertension and obesity. The relevance of these disorders as to the emergence of dementia and Alzheimer's disease is discussed based on epidemiological studies. The pathobiology of accumulation of β-amyloid and tau the hallmarks of Alzheimer's disease are discussed based on experimental data. Type 1 diabetic encephalopathy is likely to increase as a result of the global increase in the incidence of type 1 diabetes and its occurrence in increasingly younger patients. Alzheimer-like changes and dementia are not prominently increased in type 1 diabetes. Instead, the type 1 diabetic encephalopathy involves learning abilities, intelligence development and memory retrieval resulting in impaired school and professional performances. The major underlying component here appears to be insulin deficiency with downstream effects on the expression of neurotrophic factors, neurotransmitters, oxidative and apoptotic stressors resulting in defects in neuronal integrity, connectivity and loss commonly occurring in the still developing brain. Recent experimental data emphasize the role of impaired central insulin action and provide information as to potential therapies. Therefore, the underlying mechanisms resulting in diabetic encephalopathies are complex and appear to differ between the two types of diabetes. Major headway has been made in our understanding of their pathobiology; however, many questions remain to be clarified. In view of the increasing incidence of both type 1 and type 2 diabetes, intensified investigations are called for to expand our understanding of these
Tabaki, N E; Vikelis, M; Besmertis, L; Vemmos, K; Stathis, P; Mitsikostas, D D
To examine whether ideomotor apraxia exists in patients with subcortical ischemic lesions. A matched-control, prospective and multi-centered research design was used. Ideomotor apraxia, anxiety and depression were assessed by the Movement Imitation Test and the Hamilton scales, respectively. Forty two consecutive patients with subcortical ischemic stroke and an equal number of healthy participants, matched in age and sex were included. Paired-sample t-tests showed that patients had significantly more apractic elements in their movements (t = 5.03, P < 0.01), higher anxiety (t = -2.55, P = 0.0014) and depression levels (t = -2.61, P = 0.012) than their healthy matched participants. Participants with higher anxiety and depression scores performed worse on the Movement Imitation Test. Ischemic damage of subcortical modular systems may affect praxis.
Lemmon, Monica E; Donohue, Pamela K; Parkinson, Charlamaine; Northington, Frances J; Boss, Renee D
Families must process complex information related to neonatal encephalopathy and therapeutic hypothermia. In this mixed methods study, semi-structured interviews were performed with parents whose infants were enrolled in an existing longitudinal cohort study of therapeutic hypothermia between 2011 and 2014. Thematic saturation was achieved after 20 interviews. Parental experience of communicating with clinicians was characterized by 3 principle themes. Theme 1 highlighted that a fragmented communication process mirrored the chaotic maternal and neonatal course. Parents often received key information about neonatal encephalopathy and therapeutic hypothermia from maternal clinicians. Infant medical information was often given to 1 family member (60%), who felt burdened by the responsibility to relay that information to others. Families universally valued the role of the bedside nurse, who was perceived as the primary source of communication for most (75%) families. Theme 2 encompassed the challenges of discussing the complex therapy of therapeutic hypothermia: families appreciated clinicians who used lay language and provided written material, and they often felt overwhelmed by technical information that made it hard to understand the "big picture" of their infant's medical course. Theme 3 involved the uncertain prognosis after neonatal encephalopathy. Parents appreciated specific expectations about their infant's long-term development, and experienced long-term distress about prognostic uncertainty. Communicating complex and large volumes of information in the midst of perinatal crisis presents inherent challenges for both clinicians and families. We identified an actionable set of communication challenges that can be addressed with targeted interventions. Copyright © 2016 by the American Academy of Pediatrics.
Pearl, Phillip L.
Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. Selected diseases are organized by the defective molecule or mechanism and categorized as small molecule disorders (involving amino and organic acids, fatty acids, neurotransmitters, urea cycle, vitamers and cofactors, and mitochondria) and large molecule disorders (including lysosomal storage disorders, peroxisomal disorders, glycosylation disorders, and leukodystrophies). Details including key clinical features, salient electrophysiological and neuroradiological findings, biochemical findings, and treatment options are summarized for prominent disorders in each category. PMID:23762547
Okada, N; Fukunaga, M; Yamashita, F; Koshiyama, D; Yamamori, H; Ohi, K; Yasuda, Y; Fujimoto, M; Watanabe, Y; Yahata, N; Nemoto, K; Hibar, D P; van Erp, T G M; Fujino, H; Isobe, M; Isomura, S; Natsubori, T; Narita, H; Hashimoto, N; Miyata, J; Koike, S; Takahashi, T; Yamasue, H; Matsuo, K; Onitsuka, T; Iidaka, T; Kawasaki, Y; Yoshimura, R; Watanabe, Y; Suzuki, M; Turner, J A; Takeda, M; Thompson, P M; Ozaki, N; Kasai, K; Hashimoto, R
Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia. PMID:26782053
Della Puppa, Alessandro; De Pellegrin, Serena; Lazzarini, Anna; Gioffrè, Giorgio; Rustemi, Oriela; Cagnin, Annachiara; Scienza, Renato; Semenza, Carlo
Preservation of calculation processing in brain surgery is crucial for patients' quality of life. Over the last decade, surgical electrostimulation was used to identify and preserve the cortical areas involved in such processing. Conversely, subcortical connectivity among different areas implicated in this function remains unclear, and the role of surgery in this domain has not been explored so far. The authors present the first 2 cases in which the subcortical functional sites involved in calculation were identified during right parietal lobe surgery. Two patients affected by a glioma located in the right parietal lobe underwent surgery with the aid of MRI neuronavigation. No calculation deficits were detected during preoperative assessment. Cortical and subcortical mapping were performed using a bipolar stimulator. The current intensity was determined by progressively increasing the amplitude by 0.5-mA increments (from a baseline of 1 mA) until a sensorimotor response was elicited. Then, addition and multiplication calculation tasks were administered. Corticectomy was performed according to both the MRI neuronavigation data and the functional findings obtained through cortical mapping. Direct subcortical electrostimulation was repeatedly performed during tumor resection. Subcortical functional sites for multiplication and addition were detected in both patients. Electrostimulation interfered with calculation processing during cortical mapping as well. Functional sites were spared during tumor removal. The postoperative course was uneventful, and calculation processing was preserved. Postoperative MRI showed complete resection of the tumor. The present preliminary study shows for the first time how functional mapping can be a promising method to intraoperatively identify the subcortical functional sites involved in calculation processing. This report therefore supports direct electrical stimulation as a promising tool to improve the current knowledge on
Omalu, Bennet I; Fitzsimmons, Robert P; Hammers, Jennifer; Bailes, Julian
We present in this case report the tissue substrates and forensic evidence for chronic traumatic encephalopathy (CTE) in a professional American wrestler with Apolipoprotein E (apoE) genotyping. Professional wrestling is a contact-sport, with an integral risk for players to sustain repeated concussions over their careers. This case provides the first autopsy evidence of neuropathological abnormalities that accompany CTE in professional American wrestlers. A complete autopsy was performed on a 40-year-old Caucasian male, after he died unexpectedly by suicidal hanging after he had killed his wife and son. The brain showed no atrophy and no recent or remote contusions or necrosis. There was a mild to moderate neocortical neuronal dropout without any amyloid plaques. There were diffuse, sparse to frequent tau-immunoreactive Neurofibrillary Tangles and Neuropil Threads in the neocortex, subcortical ganglia, and brainstem nuclei including the substantia nigra consistent with CTE. The apoE genotype was determined to be E3/E3. Other autopsy findings included cardiomegaly, left ventricular hypertrophy, and bilateral atrioventricular dilatation; toxicologic analyses showed alprazolam and hydrocodone in the blood, and evidence of exogenous testosterone in the urine. Longitudinal studies of professional contact-sport athletes are needed to identify the differentiating characteristics of athletes who develop CTE and devise strategies for intervention.
Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi
Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji
The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain
Iadevaia, Maddalena Diana; Prete, Anna Del; Cesaro, Claudia; Gaeta, Laura; Zulli, Claudio; Loguercio, Carmelina
Hepatic encephalopathy is a challenging complication in patients with advanced liver disease. It can be defined as a neuropsychiatric syndrome caused by portosystemic venous shunting, ranging from minimal to overt hepatic encephalopathy or coma. Its pathophysiology is still unclear, although increased levels of ammonia play a key role. Diagnosis of hepatic encephalopathy is currently based on specific tests evaluating the neuropsychiatric state of patients and their quality of life; the severity of hepatic encephalopathy is measured by the West Haven criteria. Treatment of hepatic encephalopathy consists of pharmacological and corrective measures, as well as nutritional interventions. Rifaximin received approval for the treatment of hepatic encephalopathy in 2010 because of its few side effects and pharmacological benefits. The aim of this work is to review the use and efficacy of rifaximin both in acute and long-term management of hepatic encephalopathy. Treatment of overt hepatic encephalopathy involves management of the acute episode as well as maintenance of remission in those patients who have previously experienced an episode, in order to improve their quality of life. The positive effect of rifaximin in reducing health care costs is also discussed. PMID:24367227
Motojima, Yukiko; Nagura, Michiaki; Asano, Yoshitaka; Arakawa, Hiroshi; Takada, Eiko; Sakurai, Yoshio; Moriwaki, Koichi; Tamura, Masanori
Acute encephalopathy has the possibility of sequelae. While early treatment is required to prevent the development of sequelae, differential diagnosis is of the utmost priority. The aim of this study was therefore to identify parameters that can facilitate early diagnosis and prediction of outcome of acute encephalopathy. We reviewed the medical charts of inpatients from 2005 to 2011 and identified 33 patients with febrile status epilepticus. Subjects were classified into an acute encephalopathy group (n = 20) and a febrile convulsion group (n = 13), and the parameters serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), ammonia (NH3 ), cerebrospinal fluid (CSF) tau protein, and CSF interleukin-6 compared between them. Furthermore, the relationship between each parameter and prognosis was investigated in the encephalopathy group. Significant differences in serum AST, ALT, and LDH were observed between the febrile convulsion and acute encephalopathy group. Moreover, a significant difference in serum LDH was noted between the patients with and without developmental regression at the time of hospital discharge in the encephalopathy group. In particular, CSF tau protein was found to be highly likely to indicate progress, with CSF tau protein >1000 pg/dL associated with poor prognosis leading to developmental regression. Serum AST, ALT and LDH may be related to early diagnosis and prognosis, and should be carefully investigated in patients with encephalopathy. CSF tau protein could also be used as an indicator of poor prognosis in acute encephalopathy. © 2016 Japan Pediatric Society.
Botteron, Catherine; Wenker, Christian; Café-Marçal, Valeria; Oevermann, Anna; Haase, Bianca; Leeb, Tosso; Heim, Dagmar; Zurbriggen, Andreas
The first case of spongiform encephalopathy in a zebu (Bos indicus) was identified in a zoo in Switzerland. Although histopathologic and immunohistochemical analyses of the central nervous system indicated a diagnosis of bovine spongiform encephalopathy (BSE), molecular typing showed some features different from those of BSE in cattle (B. taurus). PMID:17326950
Gout, Ariel; Seibel, Nathalie; Rouvière, Constance; Husson, Béatrice; Hermans, Brigitte; Laporte, Nicole; Kadhim, Hazim; Grin, Cécile; Landrieu, Pierre; Sébire, Guillaume
The aim of this study was to further define the clinical features of subcortical aphasia in children with deep brain infarcts and to define the sequelae associated with childhood strokes. We retrospectively studied nine children with left subcortical brain infarcts who presented with acquired language disorder and underwent language investigations based on standardized tests. Stroke in these patients involved the left internal capsule, lenticular or thalamic nuclei, or a combination of these. Early aphasic manifestations following the deep cerebral infarcts affected language expression. These included mutism, nonfluent speech, word finding difficulties, and phonemic and semantic paraphasia. Speech comprehension was generally more preserved. All patients subsequently improved, although variably; sequelae such as dysfluency, word finding difficulties, and written language learning impairment could be detected through standardized tests in six of them (all younger than 6 years at the time of the infarct). Two of the three remaining patients (both older than 6 years at the time of the infarct) had a full recovery. Our study confirms the concept of childhood subcortical aphasia, depicts the linguistic profile in these patients, and sustains the indication of systematic formal language assessment during the follow-up of all children with subcortical infarct involving the dominant hemisphere.
Shakeri, Mahsa; Lombaert, Herve; Datta, Alexandre N; Oser, Nadine; Létourneau-Guillon, Laurent; Lapointe, Laurence Vincent; Martin, Florence; Malfait, Domitille; Tucholka, Alan; Lippé, Sarah; Kadoury, Samuel
Studying morphological changes of subcortical structures often predicate neurodevelopmental and neurodegenerative diseases, such as Alzheimer's disease and schizophrenia. Hence, methods for quantifying morphological variations in the brain anatomy, including groupwise shape analyses, are becoming increasingly important for studying neurological disorders. In this paper, a novel groupwise shape analysis approach is proposed to detect regional morphological alterations in subcortical structures between two study groups, e.g., healthy and pathological subjects. The proposed scheme extracts smoothed triangulated surface meshes from segmented binary maps, and establishes reliable point-to-point correspondences among the population of surfaces using a spectral matching method. Mean curvature features are incorporated in the matching process, in order to increase the accuracy of the established surface correspondence. The mean shapes are created as the geometric mean of all surfaces in each group, and a distance map between these shapes is used to characterize the morphological changes between the two study groups. The resulting distance map is further analyzed to check for statistically significant differences between two populations. The performance of the proposed framework is evaluated on two separate subcortical structures (hippocampus and putamen). Furthermore, the proposed methodology is validated in a clinical application for detecting abnormal subcortical shape variations in Alzheimer's disease. Experimental results show that the proposed method is comparable to state-of-the-art algorithms, has less computational cost, and is more sensitive to small morphological variations in patients with neuropathologies.
Spencer-Smith, Megan; Leventer, Richard; Jacobs, Rani; De Luca, Cinzia; Anderson, Vicki
Aim: Subcortical band heterotopia (SBH) or "double cortex" is a malformation of cortical development resulting from impaired neuronal migration. So far, research has focused on the neurological, neuroimaging, and genetic correlates of SBH. More recently, clinical reports and small sample studies have documented neuropsychological dysfunction in…
Spencer-Smith, Megan; Leventer, Richard; Jacobs, Rani; De Luca, Cinzia; Anderson, Vicki
Aim: Subcortical band heterotopia (SBH) or "double cortex" is a malformation of cortical development resulting from impaired neuronal migration. So far, research has focused on the neurological, neuroimaging, and genetic correlates of SBH. More recently, clinical reports and small sample studies have documented neuropsychological dysfunction in…
Peach, Richard K.; Tonkovich, John D.
Reports describing subcortical apraxia of speech (AOS) have received little consideration in the development of recent speech processing models because the speech characteristics of patients with this diagnosis have not been described precisely. We describe a case of AOS with aphasia secondary to basal ganglia hemorrhage. Speech-language symptoms…
Peach, Richard K.; Tonkovich, John D.
Reports describing subcortical apraxia of speech (AOS) have received little consideration in the development of recent speech processing models because the speech characteristics of patients with this diagnosis have not been described precisely. We describe a case of AOS with aphasia secondary to basal ganglia hemorrhage. Speech-language symptoms…
Hall, Geoffrey B. C.; West, C. Dianne; Szatmari, Peter
Recent data suggest that subthreshold presentation of emotional information is relayed to the amygdala along subcortical pathways. We examined the effect of backward masked neutral and anxious faces on the social decisions of a group of high functioning children with autism ages 7-13 years and matched controls. Participants were asked to select…
Erol, Ilknur; Saygi, Semra; Alehan, Füsun
Hashimoto's encephalopathy is an underdiagnosed, steroid-responsive, progressive or relapsing encephalopathy associated with high titers of serum antithyroid antibodies. Although Hashimoto's encephalopathy is well documented in adults, it is rarely observed or studied in children and adolescents. We describe the clinical and laboratory findings of four children (aged 9-15 years) with Hashimoto's encephalopathy. The clinical features of two patients at presentation included epileptic seizures and confusion. The other presenting signs included breath-holding spells, behavioral problems, psychosis, and ataxia (one patient each). During their presentation, three patients were euthyroid, and one was hyperthyroid. All patients manifested increased antithyroid antibodies, and all improved with steroid treatment. Hashimoto's encephalopathy is rarely suspected at presentation. Therefore, greater awareness of its signs by clinicians is necessary for proper diagnoses.
Benavente, Oscar R.; White, Carole L.; Pearce, Lesly; Pergola, Pablo; Roldan, Ana; Benavente, Marie-France; Coffey, Christopher; McClure, Leslie A.; Szychowski, Jeff M.; Conwit, Robin; Heberling, Patricia A.; Howard, George; Bazan, Carlos; Vidal-Pergola, Gabriela; Talbert, Robert; Hart, Robert G.
Background Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events. Methods Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n = 3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind – and to one of two levels of systolic blood pressure targets –‘intensive’ (<130 mmHg) vs. ‘usual’ (130–149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment. Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder. PMID:21371282
Bunday, Karen L; Tazoe, Toshiki; Rothwell, John C; Perez, Monica A
The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1-3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip.
Bunday, Karen L.; Tazoe, Toshiki; Rothwell, John C.
The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1–3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip. PMID:24849366
Englot, Dario J.; Modi, Badri; Mishra, Asht M.; DeSalvo, Matthew; Hyder, Fahmeed; Blumenfeld, Hal
Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions, or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model which, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional MRI (fMRI) that electrically-stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, while frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged upon by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures. PMID:19828814
Mallewa, Macpherson; Birbeck, Gretchen L
In addition to encountering most of the conditions treated by clinicians in the West, clinicians in the tropics are faced with unique tropical encephalopathies. These are largely but not entirely infectious in nature. Despite the relatively low cost of EEG technology, it remains unavailable in many low-income tropical settings even at the tertiary care level. Where available, the EEG recordings and interpretation are often of unacceptable quality. Nonetheless, there are existing data on the EEG patterns seen in malaria and a number of tropical viral, bacterial, and parasitic infestations.
Chamorro Fernández, A J; Marcos Martín, M; Laso Guzmán, F J
A 67-year old male was brought to the hospital by his family because he had been suffering from somnolence, bradypsychia and gait disturbance for one week. He lived alone, reported an ethanol intake higher than 100-120 g/day. His diet was limited in quality and amount. The physical examination showed stigmata of chronic liver disease. The neurological exam revealed right-side cerebellar tremor, bilateral dysmetria and gait ataxia as well as hyporeflexia in the lower limbs. He was diagnosed of Wernicke encephalopathy. How should this patient be evaluated and treated?
Sathyanarayanan, Vishwanath; Razak, Abdul; Narayan, Girish; Prabhu, Mukhyaprana; Ramachandran, Balasubramanian; Ranjini, Kudva; Vidya, Monappa; Joshi, Kusum
Posterior reversible encephalopathy syndrome (PRES) is a rare complication of nephrotic syndrome and corticosteroid therapy. Here, we discuss an 18 year old man with type 1 membranoproliferative glomerulonephritis (MPGN) secondary to hepatitis B infection who developed posterior leukoencephalopathy while on therapy with lamivudine and prednisone. He developed seizures and vision loss. He also had hypertension, but no sudden elevation was recorded at any time. Magnetic resonance imaging revealed patchy areas of altered signal intensity involving cortical gray and subcortical white matter in the bilateral frontoparietal regions, occipital cortices, temporal cortices and cerebellar hemispheres, and hyperintensity on T2W and FLAIR sequences. Tapering of prednisone and controlling hypertension resulted in clinical improvement within a few days, and in a month MRI was normal. Diagnosing PRES requires a high index of suspicion when treating similarly susceptible patients. PRES as a complication during the treatment of MPGN secondary to hepatitis B has, to our knowledge, never been reported previously in the literature.
Mizock, B A
Hepatic encephalopathy (HE) is a syndrome of global cerebral dysfunction resulting from underlying liver disease or portal-systemic shunting. HE can present as one of four syndromes, depending on the rapidity of onset of hepatic failure and the presence or absence of preexisting liver disease. The precise pathogenesis is unknown but likely involves impaired hepatic detoxification of ammonia as well as alterations in brain transport and metabolism of amino acids and amines. The etiology of malnutrition in hepatic failure is multifactorial. Nutritional deficits may be clinically manifest as marasmus or kwashiorkor, or both. Nutritional support in HE is directed toward reducing morbidity related to underlying malnutrition and concurrent disease. However, reaching nutritional goals is often complicated by protein and carbohydrate intolerance. The use of protein restriction in HE is controversial. Modified formulas that are supplemented in branched chain amino acids may be of value in patients who exhibit protein intolerance with standard feeding solutions or in patients who present with advanced degrees of encephalopathy.
Nardone, Raffaele; Taylor, Alexandra C; Höller, Yvonne; Brigo, Francesco; Lochner, Piergiorgio; Trinka, Eugen
Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of patients with liver cirrhosis. By definition, MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, but obvious clinical manifestation are lacking. MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis can be achieved through neuropsychological testing, recently developed computerized psychometric tests, such as the critical flicker frequency and the inhibitory control tests, as well as neurophysiological procedures. Event related potentials can reveal subtle changes in patients with normal neuropsychological performances. Spectral analysis of electroencephalography (EEG) and quantitative analysis of sleep EEG provide early markers of cerebral dysfunction in cirrhotic patients with MHE. Neuroimaging, in particular MRI, also increasingly reveals diffuse abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. Medical treatment for MHE to date has been focused on reducing serum ammonia levels and includes non-absorbable disaccharides, probiotics or rifaximin. Liver transplantation may not reverse the cognitive deficits associated with MHE. We performed here an updated review on epidemiology, burden and quality of life, neuropsychological testing, neuroimaging, neurophysiology and therapy in subjects with MHE. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo
Hashimoto's encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto's encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto's encephalopathy is very rare. We report a 65-year-old man who developed acute onset of cognitive decline and convulsion due to Hashimoto's encephalopathy.
Fridinger, S E; Alper, Gulay
The International Pediatric Multiple Sclerosis Study Group requires the presence of encephalopathy to diagnose acute disseminated encephalomyelitis. Clinical characteristics of encephalopathy are inadequately delineated in the pediatric demyelinating literature. The authors' purpose was to better define encephalopathy in pediatric acute disseminated encephalomyelitis by describing the details of the mental status change. A retrospective chart review was conducted for 25 children diagnosed with acute disseminated encephalomyelitis according to the International Pediatric Multiple Sclerosis Study Group guidelines. Frequency of encephalopathy-defining features was determined. Clinical characteristics, cerebrospinal fluid findings, and electroencephalography (EEG) findings were compared between patients with different stages of encephalopathy. The authors found irritability (36%), sleepiness (52%), confusion (8%), obtundation (20%), and coma (16%) as encephalopathy-defining features in acute disseminated encephalomyelitis. Twenty-eight percent had seizures, and 65% demonstrated generalized slowing on EEG. Approximately half of the patients in this study were diagnosed with encephalopathy based on the presence of irritability and/or sleepiness only. Such features in young children are often subtle and transient and thus difficult to objectively determine.
Sutter, R; Kaplan, P W
Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case-control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome. From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed. The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98-33.08], alcohol abuse (OR = 3.65, 95% CI 1.25-10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39-5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01-4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16-5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27-25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs). Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.
Nar Senol, Pelin; Bican Demir, Aylin; Bora, Ibrahim; Bakar, Mustafa
Hashimoto's encephalopathy is a rare disease which is thought to be autoimmune and steroid responsive. The syndrome is characterized by cognitive impairment, encephalopathy, psychiatric symptoms, and seizures associated with increased level of anti-thyroid antibodies. The exact pathophysiology underlying cerebral involvement is still lesser known. Although symptoms suggest a nonlesional encephalopathy in most of the cases, sometimes the clinical appearance can be subtle and may not respond to immunosuppressants or immunomodulatory agents. Here we report a case who presented with drowsiness and amnestic complaints associated with paroxysmal electroencephalography (EEG) abnormalities which could be treated only with an antiepileptic drug. PMID:27034679
Chamorro, Antonio J; Marcos-Martin, Miguel; Martin-Polo, Jorge; Garcia-Diez, Luis Carlos; Luna, Guillermo
Wernicke encephalopathy is caused by thiamine deficiency in the central nervous system, and is defined by the triad of confusional symptoms, ocular alterations and ataxia. Some other factors may also predispose alcoholic patients to this deficiency. We report two patients with hyperglicaemia and ketoacidosis due to diabetes mellitus decompensation and chronic alcoholism who developed Wernicke encephalopathy before their hospital admission. The outcome was successful after intravenous thiamine administration and insulinotherapy. The presence of Wernicke encephalopathy in alcoholics with diabetic ketoacidosis, suggests that metabolic decompensation is essential in the onset of the disease.
Radi, Z A; Thomsen, B V; Summers, B A
Renal encephalopathy was diagnosed in a 2-year-old male boar goat with a history of chronic weight loss and ataxia. Histopathological examination of the brain revealed a striking myelin vacuolation distributed mainly in two patterns: (i) along the junction of the neocortex and corona radiata, and (ii) in the bundles of the internal capsule as it dissects through the basal nuclei. The kidneys had diffuse severe tubular and glomerular necrosis and degeneration. The neural lesions are consistent with renal (uremic) encephalopathy. To the authors' knowledge, this is the first report of renal encephalopathy in a goat.
Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Yasukawa, Kumi; Takanashi, Jun-Ichi
Acute infectious encephalopathy is often observed in children in East Asia including Japan. More than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanisms in those with unclassified encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among seven patients with acute encephalopathy admitted to our hospital from June 2016 to May 2017, three were classified into acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). The other four showed consciousness disturbance lasting more than three days with no parenchymal lesion visible on MRI, which led to a diagnosis of unclassified encephalopathy. MR spectroscopy in these four patients, however, revealed an increase of glutamine with a normal N-acetyl aspartate level on days 5 to 8, which had normalized by follow-up studies on days 11 to 16. The four patients clinically recovered completely. Among 27 patients with encephalopathy, including the present seven patients, admitted to our hospital from January 2015 to March 2017, seven (26%) were classified into this type, which we propose is a new encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX). MEEX is the second most common subtype, following AESD (30%). This study suggests that excitotoxicity may be a common underlying pathomechanism of acute infectious encephalopathy, and prompt astrocytic neuroprotection from excitotoxicity may prevent progression of MEEX into AESD. Copyright © 2017 Elsevier B.V. All rights reserved.
Pasley, Brian N; Mayes, Linda C; Schultz, Robert T
Rapid identification of behaviorally relevant objects is important for survival. In humans, the neural computations for visually discriminating complex objects involve inferior temporal cortex (IT). However, less detailed but faster form processing may also occur in a phylogenetically older subcortical visual system that terminates in the amygdala. We used binocular rivalry to present stimuli without conscious awareness, thereby eliminating the IT object representation and isolating subcortical visual input to the amygdala. Functional magnetic resonance imaging revealed significant brain activation in the left amygdala but not in object-selective IT in response to unperceived fearful faces compared to unperceived nonface objects. These findings indicate that, for certain behaviorally relevant stimuli, a high-level cortical representation in IT is not required for object discrimination in the amygdala.
Ma, Tong; Wang, Congmin; Wang, Lei; Zhou, Xing; Tian, Miao; Zhang, Qiangqiang; Zhang, Yue; Li, Jiwen; Liu, Zhidong; Cai, Yuqun; Liu, Fang; You, Yan; Chen, Chao; Campbell, Kenneth; Song, Hongjun; Ma, Lan; Rubenstein, John L; Yang, Zhengang
Cortical GABAergic inhibitory interneurons have crucial roles in the development and function of the cerebral cortex. In rodents, nearly all neocortical interneurons are generated from the subcortical ganglionic eminences. In humans and nonhuman primates, however, the developmental origin of neocortical GABAergic interneurons remains unclear. Here we show that the expression patterns of several key transcription factors in the developing primate telencephalon are very similar to those in rodents, delineating the three main subcortical progenitor domains (the medial, lateral and caudal ganglionic eminences) and the interneurons tangentially migrating from them. On the basis of the continuity of Sox6, COUP-TFII and Sp8 transcription factor expression and evidence from cell migration and cell fate analyses, we propose that the majority of primate neocortical GABAergic interneurons originate from ganglionic eminences of the ventral telencephalon. Our findings reveal that the mammalian neocortex shares basic rules for interneuron development, substantially reshaping our understanding of the origin and classification of primate neocortical interneurons.
Rustemi, Oriela; Scienza, Renato; Della Puppa, Alessandro
Subcortical arteriovenous malformations (AVMs) are surgically challenging. Localization is crucial for eloquent areas, and complete resection evaluation is uncertain. Indocyanine green videoangiography (ICG-VA) can assist this surgery. An illustrative video of a subcortical frontoparietal bleeding AVM resection assisted by ICG-VA is presented. A bleeding arterial feeder aneurysm was embolized in the acute phase to protect against rebleeding. ICG-VA helped to detect the AVM's superficial arterialized draining vein, distinguishing it from normal cortical veins. This enabled a customized sulcus approach. ICG-VA showed normalized flow through the previously arterialized vein, confirming the AVM's complete resection. This applies when there is a single drainage remaining. The video can be found here: https://youtu.be/L7yJEE66kV0 .
Maslovat, Dana; Carlsen, Anthony N; Franks, Ian M
The purpose of the current study was to examine the relationship between movement preparation and excitability of subcortical motor circuits, as measured by the reflexive response to a startling acoustic stimulus. We compared the size and incidence of activation in the sternocleidomastoid (startle indicator) from participants completing either a simple or choice reaction time (RT) task. Consistent with predictions, results indicated that the startle reflex habituated after several presentations of the SAS for the choice RT group but not for the simple RT group, which we attributed to advance motor preparatory processes involved in a simple RT task. Additionally, when participants from the choice RT group were put into a simple RT condition, the startle reflex response returned to nonhabituated levels. We conclude that the increased corticospinal activation associated with advance preparation may also result in increased subcortical activation, accounting for the observed lack of habituation to a startling stimulus in simple RT.
Or, Matan; Peremans, Kathelijne; Martlé, Valentine; Vandermeulen, Eva; Bosmans, Tim; Devriendt, Nausikaa; de Rooster, Hilde
Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a (99m)technetium-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain.
Barrio, Jorge R; Small, Gary W; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A; Giza, Christopher C; Fitzsimmons, Robert P; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir
Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.
Barrio, Jorge R.; Small, Gary W.; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A.; Giza, Christopher C.; Fitzsimmons, Robert P.; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir
Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. PMID:25848027
Wade, Benjamin S.C.; Valcour, Victor G.; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Gutman, Boris A.; Thompson, Paul M.
Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%. PMID:26640768
Almairac, Fabien; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues
Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.
Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopath...
Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F
Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Chang, Jan-Shun; Chang, Tien-Chun
Both severe thyrotoxicosis and hypothyroidism may affect brain function and cause a change in consciousness, as seen with a thyroid storm or myxedema coma. However, encephalopathy may also develop in patients with autoimmune thyroid diseases independent of actual thyroid function level, and this is known as Hashimoto's encephalopathy. Although most patients are found to have Hashimoto's thyroiditis, less frequently they have Graves' disease. Clinical manifestations include epilepsy, disturbance of consciousness, cognitive impairment, memory loss, myoclonus, hallucinations, stroke-like episodes, tremor, involuntary movements, language impairment, and gait impairment. Hashimoto's encephalopathy is a relatively rare disease. As a good response can be obtained with corticosteroid therapy, early diagnosis and treatment is very beneficial for patients. Here we report three patients with Hashimoto's encephalopathy with typical manifestations of hallucinations that were associated with hypothyroidism, hyperthyroidism, and euthyroid status, respectively. They all showed a dramatic response to methylprednisolone pulse therapy.
Farrell, Ryan M; Foster, Michael B; Omoruyi, Adetokunbo O; Kingery, Suzanne E; Wintergerst, Kupper A
We report a 9-year-old female who presented with new onset intractable seizure activity followed by a prolonged encephalopathic state. After ruling out common etiologies, Hashimoto's encephalopathy (HE) was considered, and antibody levels to thyroid peroxidase and thyroglobulin were both markedly elevated in her serum. She was euthyroid at the time of presentation. Upon treatment with high dose methylprednisolone, the patient demonstrated a significant improvement in her encephalopathy. The diagnosis of HE requires strong clinical suspicion with evidence of antithyroid antibodies, as well as an encephalopathy not explained by another etiology. While well documented in the adult literature, only a handful of pediatric cases have been described to date. Patients with HE have a nearly universal response to high dose glucocorticoids. HE should be considered in the differential diagnosis of any patient, adult or pediatric, who displays prolonged, unexplainable encephalopathy.
Khavinson, V Kh; Morozov, V G; Rybnikov, V Iu; Zakutskiĭ, N G
A clinical trial of cortexin, a new peptide bioregulator of cerebral functions, in combined therapy of dyscirculatory encephalopathy (DE) stage I-II was made in 76 patients. They were divided into two groups: a control group of 31 patients on standard therapy and the study group of 45 patients on standard therapy with adjuvant cortexin delivered via nasal electrophoresis (NE). The effect was estimated by clinical symptoms, psychophysiological tests, computed EEG, quantitative parameters of rehabilitation. Cortexin NE produced a positive effect on psychoemotional state, neurological status, intellectual-mnestic and CNS functions. Adjuvant cortexin aroused efficiency of rehabilitation in DE stage I and II by 22.7%. The response of intellectual-mnestic and CNS functions was the highest. Cortexin improves attention, perception, memory, thinking, cortical neurodynamic processes. It is well tolerated and has no side effects. Cortexin is recommended as a drug of choice in combined treatment of patients with DE stage I-II.
Iverson, Grant L
For nearly 80 years, suicidality was not considered to be a core clinical feature of chronic traumatic encephalopathy (CTE). In recent years, suicide has been widely cited as being associated with CTE, and now depression has been proposed to be one of three core diagnostic features alongside cognitive impairment and anger control problems. This evolution of the clinical features has been reinforced by thousands of media stories reporting a connection between mental health problems in former athletes and military veterans, repetitive neurotrauma, and CTE. At present, the science underlying the causal assumption between repetitive neurotrauma, depression, suicide, and the neuropathology believed to be unique to CTE is inconclusive. Epidemiological evidence indicates that former National Football League players, for example, are at lower, not greater, risk for suicide than men in the general population. This article aims to discuss the critical issues and literature relating to these possible relationships.
Hindawy, A; Gouda, A; El-Ayyadi, A; Megahed, H; Bazaraa, H
Fatty Acid Oxidation disorders represent an expanding group of inborn errors of metabolism. Clinical manifestations include episodic encephalopathy, hypoketotic hypoglycemia, Reye like episodes, hepatic, muscular, cardiac affection and sudden death. Analysis of urinary organic acids and plasma fatty acids of 44 clinically suspected patients by Gas Chromatography Mass spectrometry revealed 4 cases of Medium chain acyl-CoA dehydrogenase deficiency (MCADD), 3 cases of Very long chain acyl-CoA dehydrogenase deficiency, 9 cases of multiple defects of acyl-CoA dehydrogenation in addition to 3 patients with other metabolic disorders. Timely detection of these disorders including screening for MCADD can have a favorable impact on the outcome of these patients (Tab. 11, Fig. 3, Ref. 24) Full Text (Free, PDF).
Liver cirrhosis is a worldwide gastroenterological condition, characterized by a slow, progressive and irreversible replacement of liver cells by fibrous tissue (scar) that prevents liver function. This condition often leads to the development of other syndromes. Cardiac complications can be indicated through abnormal QTc interval and arrhythmias, thereby their analysis aids in the prevention of cardiovascular events. Most cirrhotic cases have abnormal laboratory values (bilirubin, albumin, AST, ALT, AST/ALT, INR) indicating the presence of concomitant infection, inflammation and coagulopathy. In this case report, the usage Halstead-Reitan and Child-Pugh score helped in the assessment of the status of deterioration of brain. The knowledge of liver cirrhosis aetiologies help to determine the predisposition to development of hepatic encephalopathy and cardiomyopathy. The different values of liver enzymes and other blood laboratory analyses indicated the level of liver damage and poor prognosis.
Kotha, V.K.; De Souza, A.
Wernicke's encephalopathy (WE) due to causes other than chronic alcohol abuse is an uncommon and often misdiagnosed condition. In the setting of hyperemesis gravidarum, an acute deficiency of thiamine results from body stores being unable to meet increased metabolic demands. The condition produces typical clinical and radiological findings and when diagnosed early and treated promptly has a good prognosis. Magnetic resonance imaging (MRI) is sensitive and specific for diagnosis. We describe three patients with hyperemesis gravidarum who developed WE, and highlight a range of clinical and imaging features important for appropriate diagnosis. A high degree of clinical suspicion is essential. Treatment is often empirical pending results of investigation, and consists of parenteral repletion of thiamine stores. Reversal of MRI findings parallels clinical improvement. Neurologic outcomes are usually good, but half the pregnancies complicated by this condition do not produce healthy children. PMID:23859165
... progressive loss of memory and cognitive ability, subtle personality changes, inability to concentrate, lethargy, and progressive loss ... progressive loss of memory and cognitive ability, subtle personality changes, inability to concentrate, lethargy, and progressive loss ...
Shankaran, Seetha; McDonald, Scott A.; Vohr, Betty R.; Hintz, Susan R.; Ehrenkranz, Richard A.; Tyson, Jon E.; Yolton, Kimberly; Das, Abhik; Bara, Rebecca; Hammond, Jane; Higgins, Rosemary D.
OBJECTIVES: To describe the spectrum of cognitive outcomes of children with and without cerebral palsy (CP) after neonatal encephalopathy, evaluate the prognostic value of early developmental testing and report on school services and additional therapies. METHODS: The participants of this study are the school-aged survivors of the National Institute of Child Health and Human Development Neonatal Research Network randomized controlled trial of whole-body hypothermia. Children underwent neurologic examinations and neurodevelopmental and cognitive testing with the Bayley Scales of Infant Development–II at 18 to 22 months and the Wechsler intelligence scales and the Neuropsychological Assessment–Developmental Neuropsychological Assessment at 6 to 7 years. Parents were interviewed about functional status and receipt of school and support services. We explored predictors of cognitive outcome by using multiple regression models. RESULTS: Subnormal IQ scores were identified in more than a quarter of the children: 96% of survivors with CP had an IQ <70, 9% of children without CP had an IQ <70, and 31% had an IQ of 70 to 84. Children with a mental developmental index <70 at 18 months had, on average, an adjusted IQ at 6 to 7 years that was 42 points lower than that of those with a mental developmental index >84 (95% confidence interval, −49.3 to −35.0; P < .001). Twenty percent of children with normal IQ and 28% of those with IQ scores of 70 to 84 received special educational support services or were held back ≥1 grade level. CONCLUSIONS: Cognitive impairment remains an important concern for all children with neonatal encephalopathy. PMID:25713280
Pappas, Athina; Shankaran, Seetha; McDonald, Scott A; Vohr, Betty R; Hintz, Susan R; Ehrenkranz, Richard A; Tyson, Jon E; Yolton, Kimberly; Das, Abhik; Bara, Rebecca; Hammond, Jane; Higgins, Rosemary D
To describe the spectrum of cognitive outcomes of children with and without cerebral palsy (CP) after neonatal encephalopathy, evaluate the prognostic value of early developmental testing and report on school services and additional therapies. The participants of this study are the school-aged survivors of the National Institute of Child Health and Human Development Neonatal Research Network randomized controlled trial of whole-body hypothermia. Children underwent neurologic examinations and neurodevelopmental and cognitive testing with the Bayley Scales of Infant Development-II at 18 to 22 months and the Wechsler intelligence scales and the Neuropsychological Assessment-Developmental Neuropsychological Assessment at 6 to 7 years. Parents were interviewed about functional status and receipt of school and support services. We explored predictors of cognitive outcome by using multiple regression models. Subnormal IQ scores were identified in more than a quarter of the children: 96% of survivors with CP had an IQ <70, 9% of children without CP had an IQ <70, and 31% had an IQ of 70 to 84. Children with a mental developmental index <70 at 18 months had, on average, an adjusted IQ at 6 to 7 years that was 42 points lower than that of those with a mental developmental index >84 (95% confidence interval, -49.3 to -35.0; P < .001). Twenty percent of children with normal IQ and 28% of those with IQ scores of 70 to 84 received special educational support services or were held back ≥1 grade level. Cognitive impairment remains an important concern for all children with neonatal encephalopathy. Copyright © 2015 by the American Academy of Pediatrics.
Kim, Tae Eun; Lee, Eun Ja; Young, Jeong Bo; Shin, Dong Jae; Kim, Ji Hoon
Ethanol causes diverse neurologic conditions caused by acute and chronic brain damage. This review provides an overview of Wernicke encephalopathy and other ethanol-related brain changes, such as chronic brain atrophy, Marchiafava-Bignami disease, osmotic demyelination syndrome, chronic hepatic encephalopathy, and acute alcohol withdrawal. As clinical symptoms of this spectrum of diseases have nonspecific neurologic alterations, radiologists should have current radiologic information and understand the imaging findings pertaining to the pathophysiology to support diagnosis.
Isono, O; Araki, S; Shiota, J; Toyota, S; Sugita, K
A fifty-nine-year-old alcoholic man with severe hypoglycemic encephalopathy was examined using sequential CT scans of the brain (CT). Twenty-seven hours after the attack, which resulted in a comatose state, CT disclosed multiple low density areas throughout the cerebral cortex which resembled multiple cortical infarctions. CT obtained four days after the ictus demonstrated more prominent low density areas in the cerebral cortex, diffuse cerebral edema and partial cortical enhancement after administration of contrast medium. Sixteen days after the ictus, the multiple low density areas in the cerebral cortex disappeared. Enhanced CT on day 23 demonstrated marked gyral enhancement throughout the cerebral cortex. Thereafter diffuse brain atrophy progressed rapidly as demonstrated by MRI on day 82 which showed extensive cortical and subcortical atrophy particularly in the frontoparietal and parieto-occipital regions bilaterally with dilated lateral ventricles. Hypoglycemia and anoxia have long been thought to give rise to similar types of brain damage based on neuropathological observations. But it has recently been shown that they are quite different based on neurochemical and neurophysiological findings. Numerous previously reported autopsy cases of hypoglycemia confirm these findings which are neuropathologically similar to the multiple infarction seen in the present case. We conclude that the acute cortical changes of the present case are specific for hypoglycemic encephalopathy. The findings indicate that the basic mechanisms operating in hypoglycemia and anoxia are different.
Granata, Guido; Greco, Antonio; Iannella, Giannicola; Granata, Massimo; Manno, Alessandra; Savastano, Ersilia; Magliulo, Giuseppe
Posterior reversible encephalopathy syndrome is a rare clinicoradiological entity characterized by typical MRI findings located in the occipital and parietal lobes, caused by subcortical vasogenic edema. It was first described as a distinctive syndrome by Hinchey in 1996. Etiopathogenesis is not clear, although it is known that it is an endotheliopathy of the posterior cerebral vasculature leading to failed cerebral autoregulation, posterior edema and encephalopathy. A possible pathological activation of the immune system has been recently hypothesized in its pathogenesis. At clinical onset, the most common manifestations are seizures, headache and visual changes. Besides, tinnitus and acute vertigo have been frequently reported. Symptoms can be reversible but cerebral hemorrhage or ischemia may occur. Diagnosis is based on magnetic resonance imaging, in the presence of acute development of clinical neurologic symptoms and signs and arterial hypertension and/or toxic associated conditions with possible endotheliotoxic effects. Mainstay on the treatment is removal of the underlying cause. Further investigation and developments in endothelial cell function and in neuroimaging of cerebral blood flow are needed and will help to increase our understanding of pathophysiology, possibly suggesting novel therapies.
Chen, Hua-Jun; Shi, Hai-Bin; Jiang, Long-Feng; Li, Lan; Chen, Rong
To investigate structural brain connectome alterations in cirrhotic patients with prior overt hepatic encephalopathy (OHE). Seventeen cirrhotic patients with prior OHE (prior-OHE), 18 cirrhotic patients without prior OHE (non-prior-OHE) and 18 healthy controls (HC) underwent diffusion tensor imaging. Neurocognitive functioning was assessed with Psychometric Hepatic Encephalopathy Score (PHES). Using a probabilistic fibre tracking approach, we depicted the whole-brain structural network as a connectivity matrix of 90 regions (derived from the Automated Anatomic Labeling atlas). Graph theory-based analyses were performed to analyse topological properties of the brain network. The analysis of variance showed significant group effects on several topological properties, including network strength, global efficiency and local efficiency. A progressive decrease trend for these metrics was found from non-prior-OHE to prior-OHE, compared with HC. Among the three groups, the regions with altered nodal efficiency were mainly distributed in the frontal and occipital cortices, paralimbic system and subcortical regions. The topological metrics, such as network strength and global efficiency, were correlated with PHES among cirrhotic patients. The cirrhotic patients developed structural brain connectome alterations; this is aggravated by prior OHE episode. Disrupted topological organization of the brain structural network may account for cognitive impairments related to prior OHE. • Altered structural brain connectome is found in cirrhotic patients. • Structural brain connectome alterations could be aggravated by prior-OHE episode. • Altered structural brain connectome may account for cognitive impairments associated with prior OHE.
Harvey, Brian H
Metabolic encephalopathy is an acute disturbance in cellular metabolism in the brain evoked by conditions of hypoxia, hypoglycaemia, oxidative stress and/or inflammation. It usually develops acutely or subacutely and is reversible if the systemic disorder is treated. If left untreated, however, metabolic encephalopathy may result in secondary structural damage to the brain. Most encephalopathies are present with neuropsychiatric symptoms, one in particular being depression. However, mood disorders are often co-morbid with cardiovascular, liver, kidney and endocrine disorders, while increasing evidence concurs that depression involves inflammatory and neurodegenerative processes. This would suggest that metabolic disturbances resembling encephalopathy may underscore the basic neuropathology of depression at a far deeper level than currently realized. Viewing depression as a form of encephalopathy, and exploiting knowledge gleaned from our understanding of the neurochemistry and treatment of metabolic encephalopathy, may assist in our understanding of the neurobiology of depression, but also in realizing new ideas in the pharmacotherapy of mood disorders. Copyright 2008 John Wiley & Sons, Ltd.
Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Honda, Takafumi; Yasukawa, Kumi; Takanashi, Jun-Ichi
Acute infectious encephalopathy is very frequently observed in children in East Asia including Japan. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype in Japan; however, more than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanism in those with unclassified acute encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among 20 patients with acute encephalopathy admitted to our hospital during January 2015 to May 2016, 12 could not be classified into specific syndromes. MR spectroscopy was performed in 8 of these 12 patients with unclassified encephalopathy. MR spectroscopy showed an increase of glutamine with a normal N-acetyl aspartate level on days 3 to 8 in three of the 8 patients, which had normalized by follow-up studies. The three patients clinically recovered completely. This study suggests that excitotoxicity may be the underlying pathomechanism in some patients with unclassified mild encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.
Barrett, Matthew J; Login, Ivan S
To report a case of acute encephalopathy associated with ingestion of gemifloxacin, a fluoroquinolone. A 67-year-old woman presented to the emergency department with an acute alteration in mental status. Twenty-four hours earlier she had taken one 320-mg tablet of her husband's gemifloxacin prescription to treat symptoms of a mild upper respiratory infection. During her initial evaluation at our institution, the woman was dysphasic, unable to follow commands, and agitated, suggesting encephalopathy. A thorough diagnostic investigation did not reveal any structural, metabolic, or infectious etiology. Her mental status returned to normal within 2 days without any definitive treatment. Fluoroquinolone-associated neurotoxicity may manifest as encephalopathy, seizures, confusion, or toxic psychosis. To date, none of these adverse effects, specifically encephalopathy, has been reported with gemifloxacin. An objective causality assessment revealed that encephalopathy was probably associated with gemifloxacin use. Seizures, either convulsive or nonconvulsive, may have contributed to our patient's presentation, but she denied seizures prior to this event and did not suffer a seizure in the 18 months following her discharge. However, her second electroencephalograph revealed an underlying predisposition to seizures, which gemifloxacin may have unmasked. This report illustrates that severe central nervous system adverse effects associated with some fluoroquinolones may also occur with gemifloxacin. Gemifloxacin and other fluoroquinolones should be considered in the etiologic evaluation of patients with acute encephalopathy.
Omalu, Bennet; Bailes, Julian; Hamilton, Ronald L; Kamboh, M Ilyas; Hammers, Jennifer; Case, Mary; Fitzsimmons, Robert
We define chronic traumatic encephalopathy (CTE) as a progressive neurodegenerative syndrome caused by single, episodic, or repetitive blunt force impacts to the head and transfer of acceleration-deceleration forces to the brain. We present emerging histomorphologic phenotypes of CTE that we identified in our cohort of CTE cases with apolipoprotein E genotyping and causes and manners of death. Autopsy brain tissue of 14 professional athletes and 3 high school football players was examined after unexpected deaths. Histochemical and immunohistochemical tissue staining was performed with apolipoprotein E genotyping. Ten of 14 professional athletes (71%) were positive for CTE: 7 of 8 football players, 2 of 4 wrestlers, and 1 boxer. One of 3 high school players manifested incipient CTE. The age range of those with CTE was 18 to 52 years; they were all male athletes. In all cases of CTE, Alzheimer-type cerebral cortical atrophy was absent; negligible to mild neocortical neuronal dropout was present. The fundamental neuropathologic feature of CTE was the topographic distribution of sparse, moderate, and frequent band-shaped, flame-shaped, small and large globose neurofibrillary tangles and neuritic threads in the cerebral cortex, subcortical nuclei/basal ganglia, hippocampus, and brainstem nuclei. Sparse to frequent diffuse amyloid plaques may accompany tauopathy and was seen in only 2 CTE cases. No α-synucleinopathy was present. All 7 CTE-positive professional athletes with known apolipoprotein E genotypes had at least 1 E3 allele comprising 5 E3/E3 (71%) and 2 E3/E4 (29%). Alcohol- and drug-related deaths, suicides, and accidental deaths were overrepresented in our CTE cohort. The emerging histomorphologic features of our CTE cohort may specify histologic criteria for CTE diagnosis, may identify emerging histologic variants of CTE and may facilitate more objective surveillance and accurate identification of sentinel CTE cases.
Jones, Jana E.; Jackson, Daren C.; Chambers, Karlee L.; Dabbs, Kevin; Hsu, David A.; Stafstrom, Carl E.; Seidenberg, Michael; Hermann, Bruce P.
Summary Objective Using a hypothesis driven approach, subcortical and cortical regions implicated in anxiety disorders in the general population were examined in children with recent-onset epilepsy with versus without anxiety compared to controls. This study reports frequency of anxiety disorders while examining familial, clinical and demographic variables associated with anxiety in children with epilepsy. Method Participants included 88 children with epilepsy aged 8–18 years; 25 with a current anxiety disorder and 63 children with epilepsy no current anxiety disorder. 49 controls without anxiety disorders were included. T1 volumetric MRI scans were collected; subcortical volumes and cortical thickness were computed using the FreeSurfer image analysis suite. Analyses focused on adjusted measures of subcortical volumes and cortical thickness. Results Relative to controls, larger left amygdala volumes were found in the Epilepsy Anxiety group compared to the Epilepsy No Anxiety group (p = 0.027). In the hippocampus there were no significant differences between groups. Examination of cortical thickness demonstrated that the Epilepsy Anxiety group showed thinning in left medial orbitofrontal (p=0.001), right lateral orbitofrontal (p=0.017), and right frontal pole (p=0.009). There were no differences between groups in age, sex, IQ, age of onset, medications, or duration of epilepsy. There were more family members with a history of anxiety disorders in the Epilepsy Anxiety group compared to the Epilepsy No Anxiety group (p=0.005). Significance Anxiety is a common psychiatric comorbidity in children with recent-onset epilepsy with volumetric enlargement of the amygdala and thinner cortex in orbital and other regions of prefrontal cortex, suggesting structural abnormalities in brain regions that are part of the dysfunctional networks reported in individuals with anxiety disorders in the general population. These findings are evident early in the course of epilepsy, are
Charpentier, Caroline J.; Garrett, Neil; Cohen, Michael X.; Sharot, Tali
How humans integrate information to form beliefs about reality is a question that has engaged scientists for centuries, yet the biological system supporting this process is not well understood. One of the most salient attributes of information is valence. Whether a piece of news is good or bad is critical in determining whether it will alter our beliefs. Here, we reveal a frontal–subcortical circuit in the left hemisphere that is simultaneously associated with enhanced integration of favorable information into beliefs and impaired integration of unfavorable information. Specifically, for favorable information, stronger white matter connectivity within this system, particularly between the left inferior frontal gyrus (IFG) and left subcortical regions (including the amygdala, hippocampus, thalamus, putamen, and pallidum), as well as insular cortex, is associated with greater change in belief. However, for unfavorable information, stronger connectivity within this system, particularly between the left IFG and left pallidum, putamen, and insular cortex, is associated with reduced change in beliefs. These novel results are consistent with models suggesting that partially separable processes govern learning from favorable and unfavorable information. SIGNIFICANCE STATEMENT Beliefs of what may happen in the future are important, because they guide decisions and actions. Here, we illuminate how structural brain connectivity is related to the generation of subjective beliefs. We focus on how the valence of information is related to people's tendency to alter their beliefs. By quantifying the extent to which participants update their beliefs in response to desirable and undesirable information and relating those measures to the strength of white matter connectivity using diffusion tensor imaging, we characterize a left frontal–subcortical system that is associated simultaneously with greater belief updating in response to favorable information and reduced belief
Wang, Jianhong; Zhang, Jun; Xu, Lan; Shi, Yunbo; Wu, Xunyi; Guo, Qihao
Hashimoto's encephalopathy is considered as a treatable dementia, but it is often misdiagnosed. We investigated cognitive impairment and the MRI pathology of Hashimoto's encephalopathy patients. The study comprised eight patients with Hashimoto's encephalopathy, 16 patients with mild Alzheimer's disease and 24 healthy subjects. A neuropsychological battery included assessments of memory, language, attention, executive function and visuospatial ability. Cranial MRI was obtained from all Hashimoto's encephalopathy patients. Hashimoto's encephalopathy and mild Alzheimer's disease showed cognitive impairments in episodic memory, attention, executive function and visuospatial ability, but naming ability was unaffected in Hashimoto's encephalopathy. The MRI of Hashimoto's encephalopathy showed leukoencephalopathy-like type or limbic encephalitis-like type; the lesions did not affect the temporal cortex which plays a role in naming ability. Except that the naming ability was retained, the impairments in cognitive functions for the Hashimoto's encephalopathy patients were similar to those of Alzheimer's disease patients. These results were consistent with the MRI findings.
Sehatpour, Pejman; Long, Jun; Gui, Weihua; Qiao, Jianping; Javitt, Daniel C.; Wang, Zhishun
A failure of adaptive inference—misinterpreting available sensory information for appropriate perception and action—is at the heart of clinical manifestations of schizophrenia, implicating key subcortical structures in the brain including the hippocampus. We used high-resolution, three-dimensional (3D) fractal geometry analysis to study subtle and potentially biologically relevant structural alterations (in the geometry of protrusions, gyri and indentations, sulci) in subcortical gray matter (GM) in patients with schizophrenia relative to healthy individuals. In particular, we focus on utilizing Fractal Dimension (FD), a compact shape descriptor that can be computed using inputs with irregular (i.e., not necessarily smooth) surfaces in order to quantify complexity (of geometrical properties and configurations of structures across spatial scales) of subcortical GM in this disorder. Probabilistic (entropy-based) information FD was computed based on the box-counting approach for each of the seven subcortical structures, bilaterally, as well as the brainstem from high-resolution magnetic resonance (MR) images in chronic patients with schizophrenia (n = 19) and age-matched healthy controls (n = 19) (age ranges: patients, 22.7–54.3 and healthy controls, 24.9–51.6 years old). We found a significant reduction of FD in the left hippocampus (median: 2.1460, range: 2.07–2.18 vs. median: 2.1730, range: 2.15–2.23, p<0.001; Cohen’s effect size, U3 = 0.8158 (95% Confidence Intervals, CIs: 0.6316, 1.0)), the right hippocampus (median: 2.1430, range: 2.05–2.19 vs. median: 2.1760, range: 2.12–2.21, p = 0.004; U3 = 0.8421 (CIs: 0.5263, 1)), as well as left thalamus (median: 2.4230, range: 2.40–2.44, p = 0.005; U3 = 0.7895 (CIs: 0.5789, 0.9473)) in schizophrenia patients, relative to healthy individuals. Our findings provide in-vivo quantitative evidence for reduced surface complexity of hippocampus, with reduced FD indicating a less complex, less regular GM
Bebbere, D; Masala, L; Albertini, D F; Ledda, S
The subcortical maternal complex (SCMC) is a multiprotein complex uniquely expressed in mammalian oocytes and early embryos, essential for zygote progression beyond the first embryonic cell divisions. Similiar to other factors encoded by maternal effect genes, the physiological role of SCMC remains unclear, although recent evidence has provided important molecular insights into different possible functions. Its potential involvement in human fertility is attracting increasing attention; however, the complete story is far from being told. The present mini review provides an overview of recent findings related to the SCMC and discusses its potential physiological role/s with the aim of inspiring new directions for future research.
Nadeau, S E
The diagnostic evaluation of dementia is directed toward the identification of treatable causes. It can be facilitated by classification of the dementia into one of four categories: attentional, amnestic, cognitive, and intentional. Intentional dementia reflects dysfunction of frontal lobe systems, components of which include the frontal cortex, basal ganglia, thalamus, limbic structures, and subcortical white matter. Disorders that affect one or more of these components and produce intentional dementia include Binswanger's disease, Parkinson's disease, Huntington's disease, HIV infection, closed head injury, normal pressure hydrocephalus, neoplasms, syphilis, vitamin B12 deficiency, multiple sclerosis, and a number of uncommon degenerative and acquired syndromes. Depression may resemble intentional dementia. Guidelines for diagnosis and management are discussed.
Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis
Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features
Saulle, Michael; Greenwald, Brian D
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE.
Saulle, Michael; Greenwald, Brian D.
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is a long-term consequence of single or repetitive closed head injuries for which there is no treatment and no definitive pre-mortem diagnosis. It has been closely tied to athletes who participate in contact sports like boxing, American football, soccer, professional wrestling and hockey. Risk factors include head trauma, presence of ApoE3 or ApoE4 allele, military service, and old age. It is histologically identified by the presence of tau-immunoreactive NFTs and NTs with some cases having a TDP-43 proteinopathy or beta-amyloid plaques. It has an insidious clinical presentation that begins with cognitive and emotional disturbances and can progress to Parkinsonian symptoms. The exact mechanism for CTE has not been precisely defined however, research suggest it is due to an ongoing metabolic and immunologic cascade called immunoexcitiotoxicity. Prevention and education are currently the most compelling way to combat CTE and will be an emphasis of both physicians and athletes. Further research is needed to aid in pre-mortem diagnosis, therapies, and support for individuals and their families living with CTE. PMID:22567320
Riggio, Oliviero; Ridola, Lorenzo; Pasquale, Chiara
Type-C hepatic encephalopathy (HE) is a severe complication of cirrhosis, which seriously affects quality of life and is strongly related to patient survival. Treatment based on a classical pharmacological approach that is aimed at reducing the production of gut-derived toxins, such as ammonia, is still under debate. Currently, results obtained from clinical trials do not support any specific treatment for HE and our competence in testing old and new treatment modalities by randomized controlled trials with appropriate clinically relevant end-points urgently needs to be improved. On the other hand, patients who are at risk for HE are now identifiable, based on studies on the natural history of the disease. Today, very few studies that are specifically aimed at establishing whether HE may be prevented are available or in progress. Recent studies have looked at non absorbable disaccharides or antibiotics and other treatment modalities, such as the modulation of intestinal flora. In the treatment of severe stage HE, artificial liver supports have been tested with initial positive results but more studies are needed.
Mannix, Rebekah; Zafonte, Ross; Pascual-Leone, Alvaro
Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. PMID:26253448
Meehan, William; Mannix, Rebekah; Zafonte, Ross; Pascual-Leone, Alvaro
Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations.
Fraile, Pilar; Cacharro, Luis Maria; Garcia-Cosmes, Pedro; Rosado, Consolacion; Tabernero, Jose Matias
Lanthanum carbonate is a nonaluminum, noncalcium phosphate-binding agent, which is widely used in patients with end-stage chronic kidney disease. Until now, no significant side-effects have been described for the clinical use of lanthanum carbonate, and there are no available clinical data regarding its tissue stores. Here we report the case of a 59-year-old patient who was admitted with confusional syndrome. The patient received 3750 mg of lanthanum carbonate daily. Examinations were carried out, and the etiology of the encephalopathy of the patient could not be singled out. The lanthanum carbonate levels in serum and cerebrospinal fluid were high, and the syndrome eased after the drug was removed. The results of our study confirm that, in our case, the lanthanum carbonate did cross the blood-brain barrier (BBB). Although lanthanum carbonate seems a safe drug with minimal absorption, this work reveals the problem derived from the increase of serum levels of lanthanum carbonate, and the possibility that it may cross the BBB. Further research is required on the possible pathologies that increase serum levels of lanthanum carbonate, as well as the risks and side-effects derived from its absorption.
Sergeeva, Olga A
Hepatic encephalopathy (HE)(1) is a neuropsychiatric disorder caused by chronic or acute liver failure. Nearly thirty years ago a hypothesis was formulated explaining the neuropathology of HE by increased GABAergic tone. Recent progress in the GABAA-receptor (GABAAR) molecular pharmacology and biochemistry as well as the physiology of GABAergic transmission provided better understanding of GABA's role in health and disease. A detailed analysis of neuronal populations and their GABAergic afferents affected in HE is still missing. The slow progress in understanding the pathology of GABAergic transmission in HE is due to the high complexity of brain circuitries controlled by multiple types of GABAergic interneurons and the large variety of GABAAR, which are differently affected by pathological conditions and not yet fully identified. The mechanisms of action of the GABAAR agonist taurine, allosteric positive modulators (inhibitory neurosteroids, anaesthetics, benzodiazepines and histamine) and inhibitors of the GABAAR (excitatory neurosteroids, Ro15-4513) are discussed with respect to HE pathophysiology. Perspectives for GABAergic drugs in the symptomatic treatment of HE are suggested.
Salazar, R; Mehta, C; Zaher, N; Miller, D
We present a 59-year-old male with early manifestation of opsoclonus associated with gait ataxia as a rare clinical presentation of Hashimoto's encephalopathy. Empiric use of intravenous immunoglobulin followed by intravenous high dose methylprednisolone was initiated with subsequent remittance of opsoclonus, encephalopathy, ataxia, and tremor. Extensive workup for infectious, autoimmune, and paraneoplastic etiologies were undertaken and all studies were negative. Thyroglobulin antibodies (312 U/mL) and thyroid peroxidase antibodies (457 U/mL) were elevated (normal <60 U/mL) with a euthyroid state (thyroid stimulating hormone 3.13 μIU/mL). Three months after intravenous steroid therapy, the concentrations of thyroglobulin and thyroid peroxidase antibodies were retested and found to have decreased considerably. Thus, with steroid therapy, the patient's opsoclonus and encephalopathy improved. We have presented a patient with a rare case of opsoclonus as the principal presenting feature of Hashimoto's encephalopathy that was incompletely responsive to intravenous immunoglobulin and resolved with corticosteroids. This report underscores the importance for clinical practitioners to maintain a high index of suspicion for Hashimoto's encephalopathy in cases of opsoclonus, especially when accompanied by an atypical presentation.
Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.
The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358
Goodro, Matt; Sameti, Mohammad; Patenaude, Brian; Fein, George
Cross-sectional age effects in normal control volunteers were investigated in 8 subcortical structures: lateral ventricles, thalamus, caudate, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Two hundred and twenty six control subjects, ranging in age from 19 to 85 years, were scanned on a 1.5T GE system (n = 184) or a 3.0T Siemens system (n = 42). Cranium-size adjusted subcortical structure volumes were estimated using FSL’s FIRST software, which is fully automated. Significant age effects were found for all volumes when the entire age range was analyzed, however the older subjects (60–85 years of age) showed a stronger correlation between age and structural volume for the ventricles, hippocampus, amygdala and accumbens than middle-aged (35–60 years of age) subjects. Middle-aged subjects were studied at both sites, and age effects in these groups were comparable, despite differences in magnet strength and acquisition systems. This agreement lends support to the validity of the image analysis tools and procedures used in the present study. PMID:22863654
Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Wen, Wei; Thalamuthu, Anbupalam; Mather, Karen A.; Zhu, Wanlin; Jiang, Jiyang; de Micheaux, Pierre Lafaye; Wright, Margaret J.; Ames, David; Sachdev, Perminder S.
This study examined the heritability of brain grey matter structures in a subsample of older adult twins (93 MZ and 68 DZ twin pairs; mean age 70 years) from the Older Australian Twins Study. The heritability estimates of subcortical regions ranged from 0.41 (amygdala) to 0.73 (hippocampus), and of cortical regions, from 0.55 (parietal lobe) to 0.78 (frontal lobe). Corresponding structures in the two hemispheres were influenced by the same genetic factors and high genetic correlations were observed between the two hemispheric regions. There were three genetically correlated clusters, comprising (i) the cortical lobes (frontal, temporal, parietal and occipital lobes); (ii) the basal ganglia (caudate, putamen and pallidum) with weak genetic correlations with cortical lobes, and (iii) the amygdala, hippocampus, thalamus and nucleus accumbens grouped together, which genetically correlated with both basal ganglia and cortical lobes, albeit relatively weakly. Our study demonstrates a complex but patterned and clustered genetic architecture of the human brain, with divergent genetic determinants of cortical and subcortical structures, in particular the basal ganglia. PMID:27595976
Gattass, Ricardo; Galkin, Thelma W; Desimone, Robert; Ungerleider, Leslie G
Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4’s connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific. J. Comp. Neurol. 522:1941–1965, 2014. PMID:24288173
Ungerleider, Leslie G.; Galkin, Thelma W.; Desimone, Robert; Gattass, Ricardo
To investigate the subcortical efferent connections of visual area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the fovea representation as well as representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that V2 projects topographically to different portions of the inferior and lateral pulvinar and to the superficial and intermediate layers of the superior colliculus. Within the pulvinar, the V2 projections terminated in fields P1, P2, and P4, with the strongest projection being in P2. Central visual field injections in V2 labeled projection zones in P1 and P2, whereas peripheral field injections labeled P1, P2, and P4. No projections were found in P3. Both central and peripheral field injections in V2 projected topographically to the superficial and intermediate layers of the superior colliculus. Projections from V2 to the pulvinar and the superior colliculus constituted cortical–subcortical loops through which circuits serving spatial attention are activated. PMID:24456395
Burgaleta, Miguel; MacDonald, Penny A; Martínez, Kenia; Román, Francisco J; Álvarez-Linera, Juan; Ramos González, Ana; Karama, Sherif; Colom, Roberto
Neuroimaging studies have revealed associations between intelligence and brain morphology. However, researchers have focused primarily on the anatomical features of the cerebral cortex, whereas subcortical structures, such as the basal ganglia (BG), have often been neglected despite extensive functional evidence on their relation with higher-order cognition. Here we performed shape analyses to understand how individual differences in BG local morphology account for variability in cognitive performance. Structural MRI was acquired in 104 young adults (45 men, 59 women, mean age = 19.83, SD = 1.64), and the outer surface of striatal structures (caudate, nucleus accumbens, and putamen), globus pallidus, and thalamus was estimated for each subject and hemisphere. Further, nine cognitive tests were used to measure fluid (Gf), crystallized (Gc), and spatial intelligence (Gv). Latent scores for these factors were computed by means of confirmatory factor analysis and regressed vertex-wise against subcortical shape (local displacements of vertex position), controlling for age, sex, and adjusted for brain size. Significant results (FDR < 5%) were found for Gf and Gv, but not Gc, for the right striatal structures and thalamus. The main results show a relative enlargement of the rostral putamen, which is functionally connected to the right dorsolateral prefrontal cortex and other intelligence-related prefrontal areas.
Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.
Seizures are a frequently encountered finding in patients seen for clinical genetics evaluations. The differential diagnosis for the cause of seizures is quite diverse and complex, and more than half of all epilepsies have been attributed to a genetic cause. Given the complexity of such evaluations, we highlight the more common causes of genetic epileptic encephalopathies and emphasize the usefulness of recent technological advances. The purpose of this review is to serve as a practical guide for clinical geneticists in the evaluation and counseling of patients with genetic epileptic encephalopathies. Common syndromes will be discussed, in addition to specific seizure phenotypes, many of which are refractory to anti-epileptic agents. Divided by etiology, we overview the more common causes of infantile epileptic encephalopathies, channelopathies, syndromic, metabolic, and chromosomal entities. For each condition, we will outline the diagnostic evaluation and discuss effective treatment strategies that should be considered. PMID:22342633
Zampieri, Fernando Godinho; Park, Marcelo; Machado, Fabio Santana; Azevedo, Luciano Cesar Pontes
Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations. PMID:22012058
Fridley, J.; Reddy, G.; Curry, D.; Agadi, S.
Pediatric epileptiform encephalopathies are a group of neurologically devastating disorders related to uncontrolled ictal and interictal epileptic activity, with a poor prognosis. Despite the number of pharmacological options for treatment of epilepsy, many of these patients are drug resistant. For these patients with uncontrolled epilepsy, motor and/or neuropsychological deterioration is common. To prevent these secondary consequences, surgery is often considered as either a curative or a palliative option. Magnetic resonance imaging to look for epileptic lesions that may be surgically treated is an essential part of the workup for these patients. Many surgical procedures for the treatment of epileptiform encephalopathies have been reported in the literature. In this paper the evidence for these procedures for the treatment of pediatric epileptiform encephalopathies is reviewed. PMID:24288601
Berdai, Mohamed Adnane; Labib, Smael; Harandou, Mustapha
Wernicke's encephalopathy is caused by severe thiamine deficiency; it is mostly observed in alcoholic patients. We report the case of a 28-year-old woman, at 17 weeks of gestational age, with severe hyperemesis gravidarum. She presented with disturbance of consciousness, nystagmus, ophthalmoplegia, and ataxia. The resonance magnetic imagery showed bilaterally symmetrical hyperintensities of thalamus and periaqueductal area. The case was managed with very large doses of thiamine. The diagnosis of Wernicke's encephalopathy was confirmed later by a low thiamine serum level. The patient was discharged home on day 46 with mild ataxia and persistent nystagmus. Wernicke's encephalopathy is a rare complication of hyperemesis gravidarum. It should be diagnosed as early as possible to prevent long-term neurological sequela or death. Thiamine supplementation in pregnant women with prolonged vomiting should be initiated, especially before parenteral dextrose infusion. Early thiamine replacement will reduce maternal morbidity and fetal loss rate. PMID:26989522
Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. Since the emergence of BSE and its pr...
Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277
Stein, Thor D; Alvarez, Victor E; McKee, Ann C
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE.
Kural, Zekiye; Ozer, Ali Fahir
Epileptic encephalopathies are motor-mental retardations or cognitive disorders secondary to epileptic seizures or epileptiform activities. Encephalopaties due to brain damage, medications, or systemic diseases are generally not in the scope of this definition, but they may rarely accompany the condition. Appropriate differential diagnosis of epileptic seizures as well as subclinical electroencephalographic discharges are crucial for management of seizures and epileptiform discharges and relative regression of cognitive deterioration in long-term followup. Proper antiepileptic drug, hormonal treatment, or i.v. immunoglobulin choice play major role in prognosis. In this paper, we evaluated the current treatment approaches by reviewing clinical electrophysiological characteristics of epileptic encephalopathies. PMID:23056934
Béranger, F; Mangé, A; Solassol, J; Lehmann, S
In this review, we describe the generation and use of cell culture models of transmissible spongiform encephalopathies, also known as prion diseases. These models include chronically prion-infected cell lines, as well as cultures expressing variable amounts of wild-type, mutated, or chimeric prion proteins. These cell lines have been widely used to investigate the biology of both the normal and the pathological isoform of the prion protein. They have also contributed to the comprehension of the pathogenic processes occurring in transmissible spongiform encephalopathies and in the development of new therapeutic approaches of these diseases.
Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K.
Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957
Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B.
Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes.…
Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Sweet, Lawrence H; Josephson, Richard; Griffith, Erica Y; Narkhede, Atul; Hughes, Joel; Gunstad, John
Cognitive impairment in heart failure (HF) is believed to in part stem from structural brain alterations, including shrinkage of subcortical regions. Fortunately, neurocognitive dysfunction in HF can be mitigated by physical activity (PA), though mechanisms for this phenomenon are unclear. PA is protective against age-related cognitive decline that may involve improved structural integrity to brain regions sensitive to aging (e.g., subcortical structures). Yet, no study has examined the benefits of PA on the brain in HF and we sought to do so and clarify related cognitive implications. Fifty older adults with HF completed a neuropsychological battery and wore an accelerometer for 7 days. All participants underwent brain MRI. This study targeted subcortical brain volume given subcortical alterations are often observed in HF and the sensitivity of PA to subcortical structures in other patient populations. Participants averaged 4348.49 (SD=2092.08) steps per day and greater daily steps predicted better attention/executive function, episodic memory, and language abilities, p's<.05. Medical and demographically adjusted regression analyses revealed higher daily steps per day predicted greater subcortical volume, with specific effects for the thalamus and ventral diencephalon, p's<.05. Greater subcortical volume was associated with better attention/executive function, p<.05. Higher daily PA was associated with increased subcortical brain volume and better cognition in older adults with HF. Longitudinal work is needed to clarify whether daily PA can attenuate brain atrophy in HF to reduce accelerated cognitive decline in this population.
Dennison, Meg; Whittle, Sarah; Yücel, Murat; Vijayakumar, Nandita; Kline, Alexandria; Simmons, Julian; Allen, Nicholas B.
Early to mid-adolescence is an important developmental period for subcortical brain maturation, but longitudinal studies of these neurodevelopmental changes are lacking. The present study acquired repeated magnetic resonance images from 60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in subcortical structure volumes.…
Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul
Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis. PMID:21757988
Albanyan, Saleh; Al Teneiji, Amal; Monfared, Nasim; Mercimek-Mahmutoglu, Saadet
BCAP31, encoded by BCAP31, is involved in the export of transmembrane proteins from the endoplasmic reticulum. Pathogenic variants in BCAP31 results in global developmental delay, dystonia, deafness and dysmorphic features in males, called deafness, dystonia, and cerebral hypomyelination (DDCH) syndrome. We report a new patient with BCAP3-associated encephalopathy, DDCH syndrome, sensorineural hearing loss, generalized dystonia, and choreoathetosis. This 3.5-year-old boy had microcephaly and failure to thrive within the first 3 months of life. His brain MRI showed bilateral increased signal intensity in globus pallidus at age 3 months raising the suspicion of mitochondrial encephalopathy. His muscle biopsy revealed pleomorphic subsarcolemmal mitochondria collection in electron microscopy. Respiratory chain enzyme activities were normal in muscle. He was enrolled to a whole exome sequencing research study, which identified a hemizygous likely pathogenic truncating variant (c.533_536dup; p.Ser180AlafsX6) in BCAP31, inherited from his mother, who had sensorineural hearing loss and normal cognitive functions. We report a new patient with BCAP31-associated encephalopathy, DDCH syndrome, mimicking mitochondrial encephalopathy. We also report a heterozygous mother who has bilateral sensorineural hearing loss. This patient's clinical features, muscle histopathology, brain MRI features, and family history were suggestive of mitochondrial encephalopathy. Whole exome sequencing research study confirmed the diagnosis of BCAP31-associated encephalopathy, DDCH syndrome. © 2017 Wiley Periodicals, Inc.
Chen, Yun-Chung; Hsiao, Cheng-Tsung; Soong, Bing-Wen; Lee, Yi-Chung
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small vessel diseases caused by a mutation in the NOTCH3 gene. The clinical manifestations of CADASIL range from single or multiple lacunar infarcts, transient ischemic attacks, dementia, migraine with aura to psychiatric disorders. The features of brain MRI of CADASIL include multiple lacunar infarcts and diffuse leukoencephalopathy, which frequently involves external capsules and anterior temporal regions. Almost all patients with CADASIL harbor cysteine-involving mutations in NOTCH3. In Taiwan, two thirds of CADASIL patients carry NOTCH3 p.R544C mutations, and only approximately 56% of patients with CADASIL have leukoencephalopathy with anterior temporal regions involvement.
Wallin, Anders; Wardlaw, Joanna M; Markus, Hugh S; Montaner, Joan; Wolfson, Leslie; Iadecola, Costantino; Zlokovic, Berislav V; Joutel, Anne; Dichgans, Martin; Duering, Marco; Schmidt, Reinhold; Korczyn, Amos D; Grinberg, Lea T; Chui, Helena C; Hachinski, Vladimir
Vascular cognitive impairment (VCI) is the diagnostic term used to describe a heterogeneous group of sporadic and hereditary diseases of the large and small blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts and progressive damage to the white matter. Patients with progressive damage to the white matter, referred to as Binswanger’s disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger’s disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood–brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This consensus statement identifies a potential set of biomarkers based on underlying pathologic changes that could facilitate diagnosis and aid patient selection for future collaborative treatment trials. PMID:26198175
Grazioplene, Rachael G; G Ryman, Sephira; Gray, Jeremy R; Rustichini, Aldo; Jung, Rex E; DeYoung, Colin G
This study examined the association between size of the caudate nuclei and intelligence. Based on the central role of the caudate in learning, as well as neuroimaging studies linking greater caudate volume to better attentional function, verbal ability, and dopamine receptor availability, we hypothesized the existence of a positive association between intelligence and caudate volume in three large independent samples of healthy adults (total N = 517). Regression of IQ onto bilateral caudate volume controlling for age, sex, and total brain volume indicated a significant positive correlation between caudate volume and intelligence, with a comparable magnitude of effect across each of the three samples. No other subcortical structures were independently associated with IQ, suggesting a specific biological link between caudate morphology and intelligence.
Amraoui, F; van Montfrans, G A; van den Born, B J H
The presence of grade III or IV hypertensive retinopathy (HRP) is considered to distinguish hypertensive urgencies from emergencies. However, case-reports suggest that these retinal changes may be lacking in patients with hypertensive encephalopathy. To assess the frequency of grade III and IV retinopathy in this hypertensive emergency, we conducted a retrospective cohort study. We retrieved 162 patients with malignant hypertension and 34 patients (17%) fulfilled the predefined criteria for hypertensive encephalopathy. Data on retinal examination were incomplete for 6 patients (18%), thus leaving 28 patients who were analysed for the presence or absence of grade III and IV HRP. In 9 (32%) patients with hypertensive encephalopathy, grade III or IV HRP was absent, 11 (39%) patients presented with grade III and 8 (29%) patients with grade IV retinopathy. Patients without retinal abnormalities were on average 13 years younger (P=0.05), more often black (P=0.02) and displayed lower blood pressure (BP) values (P=0.04 for systolic and diastolic BP). A substantial proportion of patients with hypertensive encephalopathy lack grade III or IV HRP. This suggests that the decision to admit these patients should not only rely on the presence of grade III and IV retinopathy alone, but should also include a careful neurological examination.
McGonigle, R. J.; Bewick, M.; Trafford, J. A.; Parsons, V.
A 26-year-old female diabetic patient developed hypertensive encephalopathy with gross neurological abnormalities complicating renal artery stenosis of her transplant kidney. The elevated blood pressure was unresponsive to medical treatment. Surgical correction of the stenoses in the renal artery cured the hypertension and renal failure and led to the patient's complete recovery. Images Fig. 1 PMID:6377286
Helbig, Ingo; Tayoun, Abou Ahmad N.
Epileptic encephalopathies are severe often intractable seizure disorders where epileptiform abnormalities contribute to a progressive disturbance in brain function. Often, epileptic encephalopathies start in childhood and are accompanied by developmental delay and various neurological and non-neurological comorbidities. In recent years, this concept has become virtually synonymous with a group of severe childhood epilepsies including West syndrome, Lennox-Gastaut syndrome, Dravet syndrome, and several other severe childhood epilepsies for which genetic factors are increasingly recognized. In the last 5 years, the field has seen a virtual explosion of gene discovery, raising the number of bona fide genes and possible candidate genes for epileptic encephalopathies to more than 70 genes, explaining 20-25% of all cases with severe early-onset epilepsies that had otherwise no identifiable causes. This review will focus on the phenotypic variability as a characteristic aspect of genetic epilepsies. For many genetic epilepsies, the phenotypic presentation can be broad, even in patients with identical genetic alterations. Furthermore, patients with different genetic etiologies can have seemingly similar clinical presentations, such as in Dravet syndrome. While most patients carry mutations in SCN1A, similar phenotypes can be seen in patients with mutations in PCDH19, CHD2, SCN8A, or in rare cases GABRA1 and STXBP1. In addition to the genotypic and phenotypic heterogeneity, both benign phenotypes and severe encephalopathies have been recognized in an increasing number of genetic epilepsies, raising the question whether these conditions represent a fluid continuum or distinct entities. PMID:27781027
This book chapter is an invited, scholarly review of the mechanism(s) of TSEs for the 2nd edition of Metabolic Encephalopathies. Each chapter in the book assumes a professional knowledge of neuroscience and biochemistry, and the focus of the book is on the metabolic basis of dise...
This book chapter is an invited, scholarly review of the mechanism(s) of TSEs for the 2nd edition of Metabolic Encephalopathies. Each chapter in the book assumes a professional knowledge of neuroscience and biochemistry, and the focus of the book is on the metabolic basis of dise...
Baluarte, H J; Gruskin, A B; Hiner, L B; Foley, C M; Grover, W D
The progressive encephalopathy observed in 5 children with chronic renal failure was clinically similar to the so-called dialysis encephalopathy of adults, except that it was not related to dialysis therapy. Renal osteodystrophy is more prevalent in children than in adults and often more severe. The attempt to control the crippling deformities of renal osteodystrophy in growing children with renal insufficiency has led to the use of large quantities of aluminum containing antacids. The encephalopathy observed in children with chronic renal failure may be related to the oral ingestion of aluminum containing compounds in the presence of persistent secondary hyperparathyroidism. We suggest that alternative methods for the adequate control of serum phosphorus levels should be sought and indications for parathyroidectomy in children reevaluated. During the past 18 mos we have lowered the dose of aluminum containing compounds to 50 to 100 mg/Kg/day in our patients with progressive renal failure and recommend parathyroidectomy. No new cases of the encephalopathy have occurred.
Behura, Sushree Sangita; Swain, Sarada Prasanna
Context: Wernicke's encephalopathy (WE) is caused by thiamine (Vitamin B1) deficiency and most commonly found in chronic alcoholism and malnutrition. Clinically, the key features are mental status disturbances (global confusion), oculomotor abnormalities, and gait disturbances (ataxia). Apart from these clinical features, we can find deficits in neuropsychological functioning in patients with WE, which is more prominent after the improvement in the physical conditions. Neuropsychological functioning includes both basic cognitive processes (i.e., attention-concentration) as well as higher order cognitive processes (i.e., memory, executive functioning, reasoning), which is much vital for the maintenance of quality of life of an individual. However, unfortunately, in most of the cases, neuropsychological functioning is ignored by the clinicians. Materials and Methods: In this study four case reports of WE have been presented. The patients were taken from the outdoor department of Mental Health Institute, S.C.B. Medical College, Cuttack, Odisha. Neuropsychological functioning was measured by administration of PGIBBD and Quality of Life was measured by WHO-QOL BREF Odia Version. Discussion: As described in the literature, among the three cardinal signs (global confusion, ataxia, and ocular sings), the first two were present in all cases, but nystagmus was present in only two cases. Memory dysfunction was so disabling that the persons were unable to maintain a good Quality of Life and occupational impairment was prominent. There are disturbances in recent, remote memory, immediate recall, delayed recall, and attention and concentration, ultimately creating both physical and mental disability. PGI-BBD findings also suggest the overall impairment in neuropsychological functioning other than memory, that is, executive functioning, visual acuity, and depth perception. Findings of WHO-QOL BREF suggest the impairment of four domains of QOL in all the cases, but the severity
Loh, Wai Yen; Connelly, Alan; Cheong, Jeanie L Y; Spittle, Alicia J; Chen, Jian; Adamson, Christopher; Ahmadzai, Zohra M; Fam, Lillian Gabra; Rees, Sandra; Lee, Katherine J; Doyle, Lex W; Anderson, Peter J; Thompson, Deanne K
Volumetric and morphometric neuroimaging studies of the basal ganglia and thalamus in pediatric populations have utilized existing automated segmentation tools including FIRST (Functional Magnetic Resonance Imaging of the Brain's Integrated Registration and Segmentation Tool) and FreeSurfer. These segmentation packages, however, are mostly based on adult training data. Given that there are marked differences between the pediatric and adult brain, it is likely an age-specific segmentation technique will produce more accurate segmentation results. In this study, we describe a new automated segmentation technique for analysis of 7-year-old basal ganglia and thalamus, called Pediatric Subcortical Segmentation Technique (PSST). PSST consists of a probabilistic 7-year-old subcortical gray matter atlas (accumbens, caudate, pallidum, putamen and thalamus) combined with a customized segmentation pipeline using existing tools: ANTs (Advanced Normalization Tools) and SPM (Statistical Parametric Mapping). The segmentation accuracy of PSST in 7-year-old data was compared against FIRST and FreeSurfer, relative to manual segmentation as the ground truth, utilizing spatial overlap (Dice's coefficient), volume correlation (intraclass correlation coefficient, ICC) and limits of agreement (Bland-Altman plots). PSST achieved spatial overlap scores ≥90% and ICC scores ≥0.77 when compared with manual segmentation, for all structures except the accumbens. Compared with FIRST and FreeSurfer, PSST showed higher spatial overlap (p FDR < 0.05) and ICC scores, with less volumetric bias according to Bland-Altman plots. PSST is a customized segmentation pipeline with an age-specific atlas that accurately segments typical and atypical basal ganglia and thalami at age 7 years, and has the potential to be applied to other pediatric datasets.
Marchesotti, Silvia; Martuzzi, Roberto; Schurger, Aaron; Blefari, Maria Laura; Del Millán, José R; Bleuler, Hannes; Blanke, Olaf
Technical advances in the field of Brain-Machine Interfaces (BMIs) enable users to control a variety of external devices such as robotic arms, wheelchairs, virtual entities and communication systems through the decoding of brain signals in real time. Most BMI systems sample activity from restricted brain regions, typically the motor and premotor cortex, with limited spatial resolution. Despite the growing number of applications, the cortical and subcortical systems involved in BMI control are currently unknown at the whole-brain level. Here, we provide a comprehensive and detailed report of the areas active during on-line BMI control. We recorded functional magnetic resonance imaging (fMRI) data while participants controlled an EEG-based BMI inside the scanner. We identified the regions activated during BMI control and how they overlap with those involved in motor imagery (without any BMI control). In addition, we investigated which regions reflect the subjective sense of controlling a BMI, the sense of agency for BMI-actions. Our data revealed an extended cortical-subcortical network involved in operating a motor-imagery BMI. This includes not only sensorimotor regions but also the posterior parietal cortex, the insula and the lateral occipital cortex. Interestingly, the basal ganglia and the anterior cingulate cortex were involved in the subjective sense of controlling the BMI. These results inform basic neuroscience by showing that the mechanisms of BMI control extend beyond sensorimotor cortices. This knowledge may be useful for the development of BMIs that offer a more natural and embodied feeling of control for the user. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
Arendt, Thomas; Brückner, Martina K; Morawski, Markus; Jäger, Carsten; Gertz, Hermann-Josef
Alzheimer's disease (AD) is a degenerative disorder where the distribution of pathology throughout the brain is not random but follows a predictive pattern used for pathological staging. While the involvement of defined functional systems is fairly well established for more advanced stages, the initial sites of degeneration are still ill defined. The prevailing concept suggests an origin within the transentorhinal and entorhinal cortex (EC) from where pathology spreads to other areas. Still, this concept has been challenged recently suggesting a potential origin of degeneration in nonthalamic subcortical nuclei giving rise to cortical innervation such as locus coeruleus (LC) and nucleus basalis of Meynert (NbM). To contribute to the identification of the early site of degeneration, here, we address the question whether cortical or subcortical degeneration occurs more early and develops more quickly during progression of AD. To this end, we stereologically assessed neurone counts in the NbM, LC and EC layer-II in the same AD patients ranging from preclinical stages to severe dementia. In all three areas, neurone loss becomes detectable already at preclinical stages and is clearly manifest at prodromal AD/MCI. At more advanced AD, cell loss is most pronounced in the NbM > LC > layer-II EC. During early AD, however, the extent of cell loss is fairly balanced between all three areas without clear indications for a preference of one area. We can thus not rule out that there is more than one way of spreading from its site of origin or that degeneration even occurs independently at several sites in parallel.
Shindo, Akihiro; Liang, Anna C; Maki, Takakuni; Miyamoto, Nobukazu; Tomimoto, Hidekazu; Lo, Eng H
Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury. PMID:25920960
Shindo, Akihiro; Liang, Anna C; Maki, Takakuni; Miyamoto, Nobukazu; Tomimoto, Hidekazu; Lo, Eng H; Arai, Ken
Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.
Omalu, Bennet; Hammers, Jennifer L; Bailes, Julian; Hamilton, Ronald L; Kamboh, M Ilyas; Webster, Garrett; Fitzsimmons, Robert P
Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of
Pereira, Inês Tomás; Agster, Kara L.; Burwell, Rebecca D.
In this study we characterized the subcortical afferents for the rat PER areas 35 and 36, POR, and the lateral and medial entorhinal areas (LEA and MEA). We analyzed 33 retrograde tract-tracing experiments distributed across the five regions. For each experiment, we estimated the total numbers, percentages, and densities of labeled cells in 36 subcortical structures and nuclei distributed across septum, basal ganglia, claustrum, amygdala, olfactory structures, thalamus, and hypothalamus. We found that the complement of subcortical inputs differs across the five regions, especially the PER and POR. The PER receives input from the reuniens, suprageniculate, and medial geniculate thalamic nuclei as well as the amygdala. Overall, the subcortical inputs to the PER are consistent with a role in perception, multimodal processing, and the formation of associations that include the motivational significance of individual items and objects. Subcortical inputs to the POR were dominated by the dorsal thalamus, particularly the lateral posterior nucleus, a region implicated in visuospatial attention. The complement of subcortical inputs to the POR is consistent with a role in representing and monitoring the local spatial context. We also report that, in addition to the PER, the LEA and the medial band of the MEA also receive strong amygdala input. In contrast, subcortical input to the POR and the MEA lateral band includes much less amygdala input and is dominated by dorsal thalamic nuclei, particularly nuclei involved in spatial information processing. Like the cortical inputs, the patterns of subcortical inputs to these regions are consistent both with the view that the dorsal hippocampus is important for spatial cognition and the ventral hippocampus is important for affective cognition, and the view that they provide considerable functional integration. We conclude that the patterns of subcortical inputs to the PER, POR, and the entorhinal LEA and MEA provide further evidence
Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A; Jackson, Clive D; Kircheis, Gerald; Lauridsen, Mette M; Montagnese, Sara; Schiff, Sami; Weissenborn, Karin
Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is no gold standard for the diagnosis of this syndrome. As these patients have, by definition, no recognizable clinical features of brain dysfunction, the primary prerequisite for the diagnosis is careful exclusion of clinical symptoms and signs. A large number of psychometric tests/test systems have been evaluated in this patient group. Of these the best known and validated is the Portal Systemic Hepatic Encephalopathy Score (PHES) derived from a test battery of five paper and pencil tests; normative reference data are available in several countries. The electroencephalogram (EEG) has been used to diagnose hepatic encephalopathy since the 1950s but, once popular, the technology is not as accessible now as it once was. The performance characteristics of the EEG are critically dependent on the type of analysis undertaken; spectral analysis has better performance characteristics than visual analysis; evolving analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test together with one of the validated alternative techniques or the EEG. Minimal hepatic encephalopathy has a detrimental effect on the well-being of patients and their care
... HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory Committee... be open to the public. Name of Committee: Transmissible Spongiform Encephalopathies Advisory... available at the following link. Transmissible Spongiform Encephalopathies Advisory Committee http://fda...
Fimm, B; Zahn, R; Mull, M; Kemeny, S; Buchwald, F; Block, F; Schwarz, M
OBJECTIVE—To investigate the role of the basal ganglia and the thalamus for basic processes of visuospatial attention METHODS—Fifteen patients with acute circumscribed vascular lesions (10 with haemorrhage and five with infarction) were included in the study. The lesions were confined exclusively to subcortical structures, such as the basal ganglia, internal capsule, and thalamus, which was confirmed by initial CT on the day of referral and MRI taken 14-28 days after clinical onset. These patients were examined with two computerised attentional tasks (one detection and one search task) measuring spatial visual attention. RESULTS—There was a clear attentional asymmetry in patients with right hemispheric lesions (RHLs) in the visual search task. Seven out of eight patients with RHLs tended to be slower and/or missed significantly more target stimuli in the left sided part of a stimulus array consisting of 25 small squares than in right sided parts, although none of these patients showed signs of visual hemineglect in the visual detection task presenting visual information simultaneously to the right and left visual hemispace. All but one of these patients showed lesions in the posterior limb of the internal capsule and the putamen. On the other hand, patients with left hemispheric lesions were not impaired in the search task with only one patient showing more contralesional omissions of target stimuli than could be expected from the behaviour of normal controls. CONCLUSIONS—The results are in line with previous results showing a dominant role of right hemispheric neuronal structures for spatial attention. Furthermore, the data suggest that even with right hemispheric subcortical lesions without cortical involvement deficits in spatial orienting of attention to the left hemispace can be seen. These asymmetries of visual attention in the absence of neglect symptoms are supposed to be caused (1) by a disruption of the motor corticostriato
Montagna, Giacomo; Imperiali, Mauro; Agazzi, Pamela; D'Aurizio, Federica; Tozzoli, Renato; Feldt-Rasmussen, Ulla; Giovanella, Luca
Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature.
The exact cellular and molecular mechanisms of sepsis-induced encephalopathy remain elusive. The breakdown of the blood-brain barrier (BBB) is considered a focal point in the development of sepsis-induced brain damage. Contributing factors for the compromise of the BBB include cytokines and chemokines, activation of the complement cascade, phagocyte-derived toxic mediators, and bacterial products. To date, we are far from fully understanding the neuropathology that develops as a secondary remote organ injury as a consequence of sepsis. However, recent studies suggest that bacterial proteins may readily cross the functional BBB and trigger an inflammatory response in the subarachnoid space, in absence of a bacterial invasion. A better understanding of the pathophysiological events leading to septic encephalopathy appears crucial to advance the clinical care for this vulnerable patient population. PMID:20565858
Riviello, J J; Halligan, G E; Dunn, S P; Widzer, S J; Foley, C M; Breningstall, G N; Grover, W D
Plasmapheresis is used for treating the complications of liver failure. We performed plasmapheresis on 6 children with hepatic encephalopathy resulting from acute hepatic failure and prospectively assessed its effects on neurologic and electrophysiologic (electroencephalography and evoked potentials) function. Clinical improvement was observed in 3 of 6 patients; changes in the serum ammonia value or the results of initial electrophysiologic tests did not predict the patient response. Two patients underwent transplantation after neurologic improvement was produced by plasmapheresis; however, despite plasmapheresis, 4 patients progressed to brain death. Our data demonstrate that plasmapheresis may transiently improve the encephalopathy of acute hepatic failure but is not curative alone. Therefore, plasmapheresis may be a useful adjunct in the treatment of liver failure, potentially improving the pretransplantation status of the patient.
Zappella, Nathalie; Perier, François; Pico, Fernando; Palette, Catherine; Muret, Alexandre; Merceron, Sybille; Girbovan, Andrei; Marquion, Fabien; Legriel, Stephane
Abstract Background: Posterior reversible encephalopathy syndrome (PRES) has well-established links with several drugs. Whether a link also exists with serotonin–norepinephrine reuptake inhibitor such as duloxetine is unclear. Methods: We report on a patient who developed PRES with a coma and myoclonus related to hypertensive encephalopathy a few days after starting duloxetine treatment. Magnetic resonance imaging was performed and catecholamine metabolites assayed. Results: The patient achieved a full recovery after aggressive antihypertensive therapy and intravenous anticonvulsant therapy. Conclusions: The clinical history, blood and urinary catecholamine and serotonin levels, and response to treatment strongly suggest that PRES was induced by duloxetine. Duloxetine should be added to the list of causes of PRES. PMID:27537580
Herrera Martínez, Aura; Viñals Torràs, Montserrat; Muñoz Jiménez, Ma Concepción; Arenas de Larriva, Antonio Pablo; Molina Puerta, Ma José; Manzano García, Gregorio; Gálvez Moreno, Ma Ángeles; Calañas-Continente, Alfonso
The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.
Kim, Young Ok; Korff, Christian M; Villaluz, Mel Michel G; Suls, Arvid; Weckhuysen, Sarah; De Jonghe, Peter; Scheffer, Ingrid E
STXBP1 encephalopathy is associated with a range of movement disorders. We observed head stereotypies in three patients. These comprised a slow (<1Hz), high-amplitude, horizontal, 'figure-of-eight' pattern, beginning at age 4-6 years and resulting in neck muscle hypertrophy, in two males; a faster (2-3Hz), side-to-side, 'no' movement, starting at the age of 9 years 6 months was observed in one female. Upper limb and truncal stereotypies and vocalization occurred intermittently with the head movements. The stereotypies increased with excitement but settled with concentration and sleep. Head and upper limb stereotypies are valuable clinical clues to the diagnosis of STXBP1 encephalopathy in patients with profound impairments. © 2013 Mac Keith Press.
Marín, E; Uribe, M
The management of hepatic encephalopathy should be considered accordingly with the precipitating factor and the type of encephalopathy. Ideally the therapeutic approach must be useful for both acute and chronic forms of encephalopathy. Current treatment of hepatic encephalopathy consists of certain well-established measures attempting to identify and treat the precipitating factors, and to reduce the intestinal nitrogenous compounds formation and absorption by dietary restriction or bowel-cleansing with catartics or antibiotics such as neomycin, metronidazol, etc. This review describes briefly several therapeutic modalities.
Hughes, Adrienne; Brown, Alisha; Valento, Matthew
Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.
Hughes, Adrienne; Brown, Alisha; Valento, Matthew
Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729
Ward, Hester J. T.; Knight, Richard S. G.
Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.
Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.
The oral administration of short (C6) and medium (C8 and (C10) chain triglycerides produced no clinical or electroencephalographic changes in patients with cirrhosis of the liver. Arterial ammonia levels were also monitored in these patients and showed no significant change after medium chain triglycerides. It was concluded that medium chain triglycerides, known to be of potential value in the treatment of malabsorption in patients with cirrhosis, are not clinically contraindicated, even in patients with evidence of hepatic encephalopathy. PMID:4841275
Fatemi, Ali; Wilson, Mary Ann; Johnston, Michael V.
Synopsis Hypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. There has been significant research progress in hypoxic-ischemic encephalopathy over the last two decades and many new molecular mechanisms have been identified. Despite all these advances, therapeutic interventions are still limited. In this review paper, we discuss a number of molecular pathways involved in hypoxia-ischemia, and potential therapeutic targets. PMID:19944838
Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray
Hepatic encephalopathy (HE) develops in about 50% of patients with cirrhosis and is one of the features of decompensated cirrhosis. The inpatient incidence of HE is approximately 23,000/year and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails two phases, induction and maintenance of remission. Most cases of significant hepatic encephalopathy are precipitated by infection, gastrointestinal bleeding, medications or other culprits. All patients should be evaluated for secondary triggers of HE and treatment should be initiated with a non-absorbable disaccharide (i.e. lactulose) in most cases. Rifaximin (off-label) can be added in patients not responding to lactulose. Neomycin is a less preferable alternative to rifaximin, due to its side effect profile. Other therapies including zinc, LOLA, and branch chain amino acids can be considered for patients not responding to a disaccharide and non-absorbable antibiotic. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe hepatic encephalopathy who do not respond to medical therapy. It is critically important that patients hospitalized with significant hepatic encephalopathy continue a maintenance medication(s) at the time of dismissal to prevent further episodes. Patients with a 1st time episode of HE can be placed on lactulose and careful instruction should be provided to patient and caregiver about titration of dose to achieve 3 bowel movements per day. Patients with recurrent HE episodes despite lactulose benefit from the addition of rifaximin which decreases the frequency of recurrent HE episodes and related hospitalizations. Lastly, patients and their families should be counselled about the risk of motor vehicle accidents which
Agadi, Satish; Quach, Michael M.
Untreated epileptic encephalopathies in children may potentially have disastrous outcomes. Treatment with antiepileptic drugs (AEDs) often may not control the seizures, and even if they do, this measure is only symptomatic and not specific. It is especially valuable to identify potential underlying conditions that have specific treatments. Only a few conditions have definitive treatments that can potentially modify the natural course of disease. In this paper, we discuss the few such conditions that are responsive to vitamin or vitamin derivatives. PMID:23984056
Goddings, Anne-Lise; Mills, Kathryn L; Clasen, Liv S; Giedd, Jay N; Viner, Russell M; Blakemore, Sarah-Jayne
Puberty is characterized by hormonal, physical and psychological transformation. The human brain undergoes significant changes between childhood and adulthood, but little is known about how puberty influences its structural development. Using a longitudinal sample of 711 magnetic resonance imaging scans from 275 individuals aged 7-20years, we examined how subcortical brain regions change in relation to puberty. Our regions of interest included the amygdala, hippocampus and corpus striatum including the nucleus accumbens (NA), caudate, putamen and globus pallidus (GP). Pubertal development was significantly related to structural volume in all six regions in both sexes. Pubertal development and age had both independent and interactive influences on volume for the amygdala, hippocampus and putamen in both sexes, and the caudate in females. There was an interactive puberty-by-age effect on volume for the NA and GP in both sexes, and the caudate in males. These findings suggest a significant role for puberty in structural brain development. © 2013. Published by Elsevier Inc. All rights reserved.
Vidyasagar, Trichur R; Jayakumar, Jaikishan; Lloyd, Errol; Levichkina, Ekaterina V
The primary visual cortex of carnivores and primates shows an orderly progression of domains of neurons that are selective to a particular orientation of visual stimuli such as bars and gratings. We recorded from single-thalamic afferent fibers that terminate in these domains to address the issue whether the orientation sensitivity of these fibers could form the basis of the remarkable orientation selectivity exhibited by most cortical cells. We first performed optical imaging of intrinsic signals to obtain a map of orientation domains on the dorsal aspect of the anaesthetized cat's area 17. After confirming using electrophysiological recordings the orientation preferences of single neurons within one or two domains in each animal, we pharmacologically silenced the cortex to leave only the afferent terminals active. The inactivation of cortical neurons was achieved by the superfusion of either kainic acid or muscimol. Responses of single geniculate afferents were then recorded by the use of high impedance electrodes. We found that the orientation preferences of the afferents matched closely with those of the cells in the orientation domains that they terminated in (Pearson's r = 0.633, n = 22, P = 0.002). This suggests a possible subcortical origin for cortical orientation selectivity. PMID:25855249
Guo, Zhihui; Kashyap, Satyananda; Sonka, Milan; Oguz, Ipek
Automated and reliable segmentation of subcortical structures from human brain magnetic resonance images is of great importance for volumetric and shape analyses in quantitative neuroimaging studies. However, poor boundary contrast and variable shape of these structures make the automated segmentation a tough task. We propose a 3D graph-based machine learning method, called LOGISMOS-RF, to segment the caudate and the putamen from brain MRI scans in a robust and accurate way. An atlas-based tissue classification and bias-field correction method is applied to the images to generate an initial segmentation for each structure. Then a 3D graph framework is utilized to construct a geometric graph for each initial segmentation. A locally trained random forest classifier is used to assign a cost to each graph node. The max-flow algorithm is applied to solve the segmentation problem. Evaluation was performed on a dataset of T1-weighted MRI's of 62 subjects, with 42 images used for training and 20 images for testing. For comparison, FreeSurfer, FSL and BRAINSCut approaches were also evaluated using the same dataset. Dice overlap coefficients and surface-to-surfaces distances between the automated segmentation and expert manual segmentations indicate the results of our method are statistically significantly more accurate than the three other methods, for both the caudate (Dice: 0.89 +/- 0.03) and the putamen (0.89 +/- 0.03).
Yamagishi, Shimpei; Otsuka, Sho; Furukawa, Shigeto; Kashino, Makio
To make sense of complex auditory scenes, the auditory system sequentially organizes auditory components into perceptual objects or streams. In the conventional view of this process, the cortex plays a major role in perceptual organization, and subcortical mechanisms merely provide the cortex with acoustical features. Here, we show that the neural activities of the brainstem are linked to perceptual organization, which alternates spontaneously for human listeners without any stimulus change. The stimulus used in the experiment was an unchanging sequence of repeated triplet tones, which can be interpreted as either one or two streams. Listeners were instructed to report the perceptual states whenever they experienced perceptual switching between one and two streams throughout the stimulus presentation. Simultaneously, we recorded event related potentials with scalp electrodes. We measured the frequency-following response (FFR), which is considered to originate from the brainstem. We also assessed thalamo-cortical activity through the middle-latency response (MLR). The results demonstrate that the FFR and MLR varied with the state of auditory stream perception. In addition, we found that the MLR change precedes the FFR change with perceptual switching from a one-stream to a two-stream percept. This suggests that there are top-down influences on brainstem activity from the thalamo-cortical pathway. These findings are consistent with the idea of a distributed, hierarchical neural network for perceptual organization and suggest that the network extends to the brainstem level.
Shi, Xiaoyan; Zhu, Hongtu; Ibrahim, Joseph G.; Liang, Faming; Lieberman, Jeffrey; Styner, Martin
The aim of this paper is to develop a semiparametric model for describing the variability of the medial representation of subcortical structures, which belongs to a Riemannian manifold, and establishing its association with covariates of interest, such as diagnostic status, age and gender. We develop a two-stage estimation procedure to calculate the parameter estimates. The first stage is to calculate an intrinsic least squares estimator of the parameter vector using the annealing evolutionary stochastic approximation Monte Carlo algorithm and then the second stage is to construct a set of estimating equations to obtain a more efficient estimate with the intrinsic least squares estimate as the starting point. We use Wald statistics to test linear hypotheses of unknown parameters and establish their limiting distributions. Simulation studies are used to evaluate the accuracy of our parameter estimates and the finite sample performance of the Wald statistics. We apply our methods to the detection of the difference in the morphological changes of the left and right hippocampi between schizophrenia patients and healthy controls using medial shape description. PMID:23794769
Guo, Zhihui; Kashyap, Satyananda; Sonka, Milan; Oguz, Ipek
Automated and reliable segmentation of subcortical structures from human brain magnetic resonance images is of great importance for volumetric and shape analyses in quantitative neuroimaging studies. However, poor boundary contrast and variable shape of these structures make the automated segmentation a tough task. We propose a 3D graph-based machine learning method, called LOGISMOS-RF, to segment the caudate and the putamen from brain MRI scans in a robust and accurate way. An atlas-based tissue classification and bias-field correction method is applied to the images to generate an initial segmentation for each structure. Then a 3D graph framework is utilized to construct a geometric graph for each initial segmentation. A locally trained random forest classifier is used to assign a cost to each graph node. The max-flow algorithm is applied to solve the segmentation problem. Evaluation was performed on a dataset of T1-weighted MRI’s of 62 subjects, with 42 images used for training and 20 images for testing. For comparison, FreeSurfer and FSL approaches were also evaluated using the same dataset. Dice overlap coefficients and surface-to-surfaces distances between the automated segmentation and expert manual segmentations indicate the results of our method are statistically significantly more accurate than the other two methods, for both the caudate (Dice: 0.89 ± 0.03) and the putamen (0.89 ± 0.03). PMID:28626291
Masliah, E.; Terry, R. D.; Alford, M.; DeTeresa, R.; Hansen, L. A.
Quantification of synaptophysinlike immunoreactivity is a valuable method for studying the presynaptic terminals in the normal and damaged nervous system. The present report shows that in the control brain, the predominant pattern of synaptic immunostaining in the neocortex was that of an evenly distributed densely granular immunolabeling of the neuropil, while in the paleocortex and in subcortical areas of the brain most of the presynaptic terminals were distributed along the dendritic arborizations or around the neuronal somata. The immunochemical and the immunohistochemical analysis of the Alzheimer's disease tissue showed that the frontal and parietal cortex presented the most severe and widespread loss, with a 45% loss in synaptophysin immunoreactivity. These areas showed an average 35% loss of large neurons. The visual cortex, hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus ceruleus displayed some degree of loss, but to a lesser extent. In addition to this loss, the basic patterns of organization of the presynaptic terminals were altered, with the presence of abundant, enlarged synaptophysin-labeled terminals. This study further supports the role of synaptic pathology in Alzheimer's disease. Images Figure 10 Figure 11 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 12 PMID:1899001
Graham, Ernest M.; Burd, Irina; Everett, Allen D.; Northington, Frances J.
Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the “liquid brain biopsy.” A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment. PMID:27468268
Kumar, Abhay; Keyrouz, Salah G; Willie, Jon T; Dhar, Rajat
Diffuse edema involving the posterior fossa may be seen with hypertensive encephalopathy and has rarely been reported to cause hydrocephalus. We present three such cases and review the literature to better delineate this uniquely reversible syndrome. Case reports and review of literature. Three patients with hypertensive encephalopathy presented to our institutions with clinical and radiographic features of obstructive hydrocephalus associated with brainstem and cerebellar edema. This required transient external drainage of cerebrospinal fluid (CSF) in two of the three patients. However, with recognition of this unusual syndrome and aggressive management of elevated blood pressure, both edema and hydrocephalus resolved. All patients made complete recoveries and did not require permanent CSF shunting. A review of the literature yielded 15 additional case reports describing reversible obstructive hydrocephalus related to hypertensive encephalopathy. All had mean arterial pressures above 130 mmHg and presented primarily with altered mental status. While half required ventriculostomy, only one required shunting. Excluding a patient who died from sepsis, all recovered neurologically once blood pressure was controlled. It is imperative to recognize such cases where hypertension causes edema within the posterior fossa resulting in secondary hydrocephalus. Focusing management on lowering blood pressure avoids unnecessary or prolonged CSF diversion.
Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M
To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (<1s) did not induce bursts. In both patients bursts were not accompanied by myoclonia. Both patients deceased. Bursts in patients with a severe postanoxic encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Wang, Beiyun; Miao, Ya; Zhao, Zhe; Zhong, Yuan
Diabetes and Alzheimer's disease are often associated with each other, whereas the relationship between two diseases is ill-defined. Although hyperglycemia during diabetes is a major cause of encephalopathy, diabetes may also cause chronic inflammatory complications including peripheral neuropathy. Hence the role and the characteristics of inflammatory macrophages in the development of diabetic encephalopathy need to be clarified. Diabetes were induced in mice by i.p. injection of streptozotocin (STZ). Two weeks after STZ injection and confirmation of development of diabetes, inflammatory macrophages were eliminated by i.p. injection of 20µg saporin-conjugated antibody against a macrophage surface marker CD11b (saporin-CD11b) twice per week, while a STZ-treated group received injection of rat IgG of same frequency as a control. The effects of macrophage depletion on brain degradation markers, brain malondialdehyde (MDA), catalase, superoxidase anion-positive cells and nitric oxide (NO) were measured. Saporin-CD11b significantly reduced inflammatory macrophages in brain, without affecting mouse blood glucose, serum insulin, glucose responses and beta cell mass. However, reduced brain macrophages significantly inhibited the STZ-induced decreases in brain MDA, catalase and superoxidase anion-positive cells, and the STZ-induced decreases in brain NO. Inflammatory macrophages may promote development of diabetic encephalopathy. © 2015 S. Karger AG, Basel.
Weckhuysen, Sarah; Ivanovic, Vanja; Hendrickx, Rik; Van Coster, Rudy; Hjalgrim, Helle; Møller, Rikke S.; Grønborg, Sabine; Schoonjans, An-Sofie; Ceulemans, Berten; Heavin, Sinead B.; Eltze, Christin; Horvath, Rita; Casara, Gianluca; Pisano, Tiziana; Giordano, Lucio; Rostasy, Kevin; Haberlandt, Edda; Albrecht, Beate; Bevot, Andrea; Benkel, Ira; Syrbe, Steffan; Sheidley, Beth; Guerrini, Renzo; Poduri, Annapurna; Lemke, Johannes R.; Mandelstam, Simone; Scheffer, Ingrid; Angriman, Marco; Striano, Pasquale; Marini, Carla; Suls, Arvid
Objectives: To determine the frequency of KCNQ2 mutations in patients with neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of KCNQ2 epileptic encephalopathy. Methods: Eighty-four patients with unexplained NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical data of 6 additional patients with KCNQ2 mutations detected by gene panel were collected. Detailed phenotyping was performed with particular attention to seizure frequency, cognitive outcome, and video-EEG. Results: In the cohort, we identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84 patients (13%). Two of 6 missense mutations detected by gene panel were recurrent and present in patients of the cohort. Seizures at onset typically consisted of tonic posturing often associated with focal clonic jerking, and were accompanied by apnea with desaturation. One patient diagnosed by gene panel had seizure onset at the age of 5 months. Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset. Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. Conclusion: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible. PMID:24107868
Hepatic encephalopathy is a common complication of hepatic cirrhosis. The clinical diagnosis is based on two concurrent types of symptoms: impaired mental status and impaired neuromotor function. Impaired mental status is characterized by deterioration in mental status with psychomotor dysfunction, impaired memory, and increased reaction time, sensory abnormalities, poor concentration, disorientation and coma. Impaired neuromotor function include hyperreflexia, rigidity, myoclonus and asterixis. The pathogenesis of hepatic encephalopathy has not been clearly defined. The general consensus is that elevated levels of ammonia and an inflammatory response work in synergy to cause astrocyte to swell and fluid to accumulate in the brain which is thought to explain the symptoms of hepatic encephalopathy. Acetyl-L-carnitine, the short-chain ester of carnitine is endogenously produced within mitochondria and peroxisomes and is involved in the transport of acetyl-moieties across the membranes of these organelles. Acetyl-L-carnitine administration has shown the recovery of neuropsychological activities related to attention/concentration, visual scanning and tracking, psychomotor speed and mental flexibility, language short-term memory, attention, and computing ability. In fact, Acetyl-L-carnitine induces ureagenesis leading to decreased blood and brain ammonia levels. Acetyl-L-carnitine treatment decreases the severity of mental and physical fatigue, depression cognitive impairment and improves health-related quality of life. The aim of this review was to provide an explanation on the possible toxic effects of ammonia in HE and evaluate the potential clinical benefits of ALC.
Thyroid hormones (TH) play crucial roles in brain maturation, neuronal migration, and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported...
Thyroid hormones (TH) play crucial roles in brain maturation, neuronal migration, and neocortical lamination. Subcortical band heterotopia (SBH) represent a class of neuronal migration errors in humans that are often associated with childhood epilepsy. We have previously reported...
Selinger, Lenka; Zarnowiec, Katarzyna; Via, Marc; Clemente, Immaculada C; Escera, Carles
A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway. Serotonin has been shown as essential for modulating the brain response to sound both cortically and subcortically, yet the genetic factors regulating this modulation regarding speech sounds have not been disclosed. We recorded the frequency following response, a biomarker of the neural tracking of speech sounds in the subcortical auditory pathway, and cortical evoked potentials in 58 participants elicited to the syllable /ba/, which was presented >2000 times. Participants with low serotonin transporter expression had higher signal-to-noise ratios as well as a higher pitch strength representation of the periodic part of the syllable than participants with medium to high expression, possibly by tuning synaptic activity to the stimulus features and hence a more efficient suppression of noise. These results imply the 5-HTTLPR in subcortical auditory speech encoding and add an important, genetically determined layer to the factors shaping the human subcortical response to speech sounds. The accurate encoding of speech sounds in the subcortical auditory nervous system is of paramount relevance for human communication, and it has been shown to be altered in different disorders of speech and auditory processing. Importantly, this encoding is plastic and can therefore be enhanced by language and music experience. Whether genetic factors
John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita
Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211
John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita
Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.
Yiş, Uluç; Scheper, Gert C; Uran, Nedret; Unalp, Aycan; Cakmakçi, Handan; Hiz-Kurul, Semra; Dirik, Eray; van der Knaap, Marjo S
Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy that is characterized by macrocephaly and a slowly progressive clinical course. It is one of the most commonly reported leukoencephalopathies in Turkey. Mutations in the MLC1 gene are the main cause of the disease. We report two patients with megalencephalic leukoencephalopathy with subcortical cysts with confirmed mutations in the MLC1 gene. The mutation in the second patient was novel. We also review identified mutations in the Turkish population.
Vinogradova, Lyudmila V; Grinenko, Olesya A
It is now recognized that both generalized and focal seizures may originate in subcortical structures. The well-known types of focal subcortically-driven seizures are gelastic seizures in patients with the hypothalamic hamartoma and sound-induced seizures in rodents with audiogenic epilepsy. The seizures are generated by subcortical intrinsically epileptogenic focus, the hamartoma in humans and the inferior colliculus (IC) in rodents. In patients with gelastic epilepsy additional seizure types may develop with time that are supposed to result from secondary epileptogenesis and spreading of epileptic discharges to the cortex. Repeated audiogenic seizures can also lead to development of additional seizure behavior and secondary epileptic activation of the cortex. This process, named audiogenic kindling, may be useful for studying secondary subcortico-cortical epileptogenesis. Using intracollicular and intracortical recordings, we studied an ictal electrographic pattern of focal subcortical seizures induced by repeated sound stimulation in Wistar audiogenic-susceptible rats. The audiogenic seizures, representing brief attacks of paroxysmal unidirectional running, were accompanied by epileptiform abnormalities in the IC, mostly on the side ipsilateral to run direction, and enhanced rhythmic 8-9Hz activity in the cortex. With repetition of the subcortical seizures and kindling development, a secondary cortical discharge began to follow the IC seizure. The secondary discharge initially involved the cortex homolateral to the side of dominant subcortical epileptiform abnormalities and behaviorally expressed as limbic (partial) clonus. Kindling progression was associated with bilateralization of the secondary cortical discharge, an increase in its amplitude and duration, intensification of associated behavioral seizures (from partial clonus to generalized tonic-clonic convulsions). Thus, ictal recordings during brief audiogenic running seizures showed their focal
Bonnier, Christine; Marique, Patricia; Van Hout, Anne; Potelle, Dominique
Traumatic brain injury is a major cause of mortality and morbidity in children younger than 15 years of age. To evaluate the role of subcortical lesions on neurodevelopmental outcomes, long-term outcomes of 50 children with severe traumatic brain injury before 4 years of age (accidental injury, n = 21, nonaccidental injury, n = 29) were reviewed retrospectively and compared with late magnetic resonance imaging (MRI) findings: no visible lesions, cortical lesions, or subcortical lesions. Subcortical lesions occurred in both accidental and nonaccidental traumatic brain injuries. Traumatic brain injury severity (initial Glasgow Coma Scale or coma duration) was significantly associated with subcortical lesions. Long-term motor or visual deficiencies occurred in one third of patients and cognitive deficiencies in 52.1%. Although deficiencies occurred without visible MRI lesions, global outcome scores, motor delay, visual impairment, head growth slowing, global intellectual quotients, and planning performances were significantly worse in patients with subcortical lesions. An alarming deterioration in intellectual quotient over time was noted. It was concluded that neurodevelopmental outcomes are worrisome after severe traumatic brain injury in young children, and subcortical lesions affect the prognosis.
Caixeta, Leonardo; Vieira, Renata Teles; Paes, Flávia; Carta, Mauro Giovanni; Nardi, Antonio Egidio; Arias-Carrión, Oscar; Rocha, Nuno B. F; Budde, Henning; Machado, Sergio
Objectives : To investigate the severity of subcortical atrophy in frontotemporal dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In addition, we aim to verify if there is correlation between demographic and clinical characteristics and subcortical atrophy in the groups. Methodology : The sample was composed of 21 patients with dementia and EPS as well as 19 patients with FTD without EPS. A linear assessment was conducted in order to identify the degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover, the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to investigate clinical aspects. Results : It was verified that patients with dementia and EPS was older than the patients with FTD (p=0.01). The severity of cognitive deficits was associated with BFI, as well as the dementia severity in the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff for normal elderly population, indicating the presence of subcortical atrophy in this group. Mean BFI was higher (although not statistically significant) in FTD group than in dementia with EPS, which can suggest at least that subcortical pathology in FTD may be as important as in the dementia with EPS group. Subcortical atrophy is a good biological marker for cognitive deterioration in FTD and in dementia with EPS. PMID:25870648
Jia, Li-Jing; Qu, Zhen-Zhen; Zhang, Xue-Qian; Tian, Yu-Juan; Wang, Ying
Uremic Encephalopathy (UE) is a neurological complication associated with acute or chronic renal failure. Imaging findings of UE may present involvement of the basal ganglia, cortical or subcortical regions, and white matter. We report a rare case of UE caused by neurogenic bladder with isolated brainstem involvement revealed by magnetic resonance imaging (MRI). Immediate therapy resulted in full recovery of neurological signs and changes on MRI. A 14-year-old Han Chinese woman with a history of chronic renal failure caused by neurogenic bladder. On admission, she was unconscious and her pupils presented different sizes, while her vital signs were normal. MRI showed high signal in the dorsal pontine base and in the mid brain on fluid-attenuated inversion-recovery (FLAIR) imaging and on T2-weighted imaging while the signal was normal on diffusion-weighted images (DWI). Blood analysis revealed renal failure and acidosis. After urinary retention treatment and acidosis correction, the patient soon recovered. Follow-up MRI 2 months after the discharge revealed complete resolution of UE in the brainstem. We reported a rare case of a patient with UE that had unusual imaging manifestations for whom timely diagnosis and treatment assured recovery.
Pedraza, María Isabel; Barbado, Julia; Ruiz, Marina; Guerrero, Ángel Luis
Introduction. Posterior Reversible Encephalopathy Syndrome (PRES) is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP) and loss of integrity of vascular endothelium related with different triggers. Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc) not previously known. Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI) showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed “active pattern,” considered typical of SSc. Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon. PMID:25802777
Stewart, Charmaine A; Enders, Felicity T B; Schneider, Niccole; Felmlee-Devine, Donna; Kamath, Patrick S; Smith, Glenn E
Minimal hepatic encephalopathy (HE) has profoundly negative effects on daily functioning ad quality of life. However, standard psychometric procedures have not been widely incorporated into efforts to develop a neuropsychological battery for this condition. To establish the construct and diagnostic validity of a neuropsychological approach for the recognition of minimal HE in patients with cirrhosis. A comprehensive battery of neuropsychological tests was administered to cirrhotic patients with at most grade 1 HE, recruited from the liver transplant and advanced liver disease clinics. An inflammatory bowel disease comparison group was similarly evaluated, thus controlling for the secondary effects of chronic illness on cognition. Testing results for the cirrhosis group were subjected to principal component analysis to establish the relevant cognitive constructs and associated measures. Factor analysis was applied to the neuropsychological battery of 20 tests to determine the cognitive factors to be used. Age-adjusted standardized neuropsychological factor scores were then compared for the two groups. Factor analysis revealed that our battery of 20 tests was measuring three cognitive factors. Based on the pattern of factor loadings, we labeled these important cognitive factors: global cognitive function; psychomotor speed; and learning and memory. Logistic regression revealed that only impaired psychomotor speed distinguished cirrhotics with no more than grade 1 HE from medically ill controls. The cirrhosis group was characterized by a pattern of preserved global cognitive functioning, mild memory impairment, and moderate psychomotor speed impairment. This distinctive pattern of focal psychomotor speed deficits is suggestive of subcortical pathway involvement in minimal HE.
Krizman, Jennifer L; Skoe, Erika; Kraus, Nina
Many sounds in the environment, including speech, are temporally dynamic. The auditory brainstem is exquisitely sensitive to temporal features of the incoming acoustic stream, and by varying the speed of presentation of these auditory signals it is possible to investigate the precision with which temporal cues are represented at a subcortical level. Therefore, to determine the effects of stimulation rate on the auditory brainstem response (ABR), we recorded evoked responses to both a click and a consonant-vowel speech syllable (/da/) presented at three rates (15.4, 10.9 and 6.9 Hz). We hypothesized that stimulus rate affects the onset to speech-evoked responses to a greater extent than click-evoked responses and that subcomponents of the speech- ABR are distinctively affected. While the click response was invariant with changes in stimulus rate, timing of the onset response to /da/ varied systematically, increasing in peak latency as presentation rate increased. Contrasts between the click- and speech-evoked onset responses likely reflect acoustic differences, where the speech stimulus onset is more gradual, has more delineated spectral information, and is more susceptible to backward masking by the subsequent formant transition. The frequency-following response (FFR) was also rate dependent, with response magnitude of the higher frequencies (>400 Hz), but not the frequencies corresponding to the fundamental frequency, diminishing with increasing rate. The selective impact of rate on high-frequency components of the FFR implicates the involvement of distinct underlying neural mechanisms for high- versus low-frequency components of the response. Furthermore, the different rate sensitivities of the speech-evoked onset response and subcomponents of the FFR support the involvement of different neural streams for these two responses. Taken together, these differential effects of rate on the ABR components likely reflect distinct aspects of auditory function such that
Krizman, Jennifer; Skoe, Erika; Kraus, Nina
Many sounds in the environment, including speech, are temporally dynamic. The auditory brainstem is exquisitely sensitive to temporal features of the incoming acoustic stream, and by varying the speed of presentation of these auditory signals it is possible to investigate the precision with which temporal cues are represented at a subcortical level. Therefore, to determine the effects of stimulation rate on the auditory brainstem response (ABR), we recorded evoked responses to both a click and a consonant-vowel speech syllable (/da/) presented at three rates (15.4, 10.9 and 6.9 Hz). We hypothesized that stimulus rate affects the onset to speech-evoked responses to a greater extent than click-evoked responses and that subcomponents of the speech-ABR are distinctively affected. While the click response was invariant with changes in stimulus rate, timing of the onset response to /da/ varied systematically, increasing in peak latency as presentation rate increased. Contrasts between the click- and speech-evoked onset responses likely reflect acoustic differences, where the speech stimulus onset is more gradual, has more delineated spectral information, and is more susceptible to backward masking by the subsequent formant transition. The frequency-following response (FFR) was also rate dependent, with response magnitude of the higher frequencies (>400 Hz), but not the frequencies corresponding to the fundamental frequency, diminishing with increasing rate. The selective impact of rate on high-frequency components of the FFR implicates the involvement of distinct underlying neural mechanisms for high- versus low-frequency components of the response. Furthermore, the different rate sensitivities of the speech-evoked onset response and subcomponents of the FFR support the involvement of different neural streams for these two responses. Taken together, these differential effects of rate on the ABR components likely reflect distinct aspects of auditory function such that
Plack, Christopher J.
Practice can lead to dramatic improvements in the discrimination of auditory stimuli. In this study, we investigated changes of the frequency-following response (FFR), a subcortical component of the auditory evoked potentials, after a period of pitch discrimination training. Twenty-seven adult listeners were trained for 10 h on a pitch discrimination task using one of three different complex tone stimuli. One had a static pitch contour, one had a rising pitch contour, and one had a falling pitch contour. Behavioral measures of pitch discrimination and FFRs for all the stimuli were measured before and after the training phase for these participants, as well as for an untrained control group (n = 12). Trained participants showed significant improvements in pitch discrimination compared to the control group for all three trained stimuli. These improvements were partly specific for stimuli with the same pitch modulation (dynamic vs. static) and with the same pitch trajectory (rising vs. falling) as the trained stimulus. Also, the robustness of FFR neural phase locking to the sound envelope increased significantly more in trained participants compared to the control group for the static and rising contour, but not for the falling contour. Changes in FFR strength were partly specific for stimuli with the same pitch modulation (dynamic vs. static) of the trained stimulus. Changes in FFR strength, however, were not specific for stimuli with the same pitch trajectory (rising vs. falling) as the trained stimulus. These findings indicate that even relatively low-level processes in the mature auditory system are subject to experience-related change. PMID:20878201
Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C
Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro-organisms, which when administered in adequate amounts, may confer a health benefit on the host. To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random-effects model meta-analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration
McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.
Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…
head injuries sustained in battle have been associated with the development of chronic traumatic encephalopathy (CTE). Pathological series have...Keywords:Traumatic Brain Injury, Chronic Traumatic Encephalopathy ,PET imaging, Tau Overall Project Summary:Preparation for enrollment...AD_________________ Award Number: W81XWH-13-1-0486 TITLE: Early Recognition of Chronic Traumatic
Owing to its susceptibility to various transmissible spongiform encephalopathies (TSE) and relatively short incubation times, the raccoon (Procyon lotor) has been suggested as a model for TSE strain differentiation. Transmissible mink encephalopathy (TME) is a prion disease of undetermined origin in...
Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques as...
McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.
Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…
Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been eluci...
Shbarou, Rolla; Mikati, Mohamad A
Pediatric epileptic encephalopathies represent a clinically challenging and often devastating group of disorders that affect children at different stages of infancy and childhood. With the advances in genetic testing and neuroimaging, the etiologies of these epileptic syndromes are now better defined. The various encephalopathies that are reviewed in this article include the following: early infantile epileptic encephalopathy or Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, West syndrome, severe myoclonic epilepsy in infancy (Dravet syndrome), Landau-Kleffner syndrome, Lennox-Gastaut syndrome, and epileptic encephalopathy with continuous spike-and-wave during sleep. Their clinical features, prognosis as well as underlying genetic etiologies are presented and updated. Copyright © 2016. Published by Elsevier Inc.
Sulaiman, Raashda Ainuddin; Shaheen, Marwan Yassin; Al-Zaidan, Hamad; Al-Hassnan, Zuhair; Al-Sayed, Moeenaldeen; Rahbeeni, Zuhair; Bakshi, Nasir Ahmed; Kaya, Namik; Aldosary, Mazhor; Al-Owain, Mohammed
Summary We report an unusual case of recurrent encephalopathy due to acquired hemophagocytic lymphohistiocytosis (HLH) in a patient with propionic acidemia (PA). PA is an inherited metabolic disorder in which patients often present with encephalopathy and pancytopenia during metabolic decompensation. However, these patients may rarely develop HLH with similar presentation. This case illustrates the need to distinguish HLH induced encephalopathy from the one secondary to metabolic decompensation in these patients, as early diagnosis and treatment of HLH improves prognosis. This case also highlights the importance of considering HLH in patients presenting with unexplained encephalopathy, as early diagnosis and treatment is lifesaving in this otherwise lethal condition. To our knowledge this is the first case report of acquired HLH presenting as recurrent encephalopathy followed by complete recovery, in a metabolically stable patient with PA. PMID:27672548
We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation. PMID:28145649
Lee, Yun Jeong; Yum, Mi Sun; Kim, Eun Hee; Kim, Min Jee; Kim, Kyung Mo; Im, Ho Joon; Kim, Young Hwue; Park, Young Seo; Ko, Tae Sung
We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0-491 days), 10 days after HT (1-296 days), 49.5 days after HSCT (9-1,405 days), and 39 days after LT (1-1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.
Savica, Rodolfo; Rabinstein, Alejandro A; Josephs, Keith A
The aim of this study was to investigate the presence of movement disorders associated with ifosfamide toxicity. One of the most common adverse events of ifosfamide treatment is central nervous system toxicity. However, little is known about the occurrence of movement disorders associated with ifosfamide toxicity. We performed a retrospective computer search of the electronic medical records database of the Mayo Clinic, Rochester, MN from 1 January 1997-30 June 2010, using a series of search terms to identify all patients that had been treated with ifosfamide for systemic cancer. Among 400 patients that have ever used ifosfamide, we selected those patients that had any neurological complication in their medical records after the use of ifosfamide. Fifty-two had a neurological complication after ifosfamide administration. The most common neurological complication was encephalopathy that was present in 11 cases (21%). The presence of a movement disorder time locked to the administration of ifosfamide was reported in seven cases (13%). Generalized myoclonus was most common, occurring in four patients while postural tremor was documented in the other three. All patients with myoclonus had asterixis. Four of the patients also had encephalopathy. In six patients the movement disorders resolved within 48 h, spontaneously, after the discontinuation of ifosfamide, while in one case resolved in 24 h after the treatment with methylene blue. Our study demonstrates that although encephalopathy is the most common adverse neurological event associated with ifosfamide toxicity, movement disorders, including generalized myoclonus, asterixis, and postural tremors may also occur. Treatment with methylene blue may be further considered as useful to ameliorate the movement disorders.
Cho, Hanna; Choi, Jae Yong; Hwang, Mi Song; Lee, Seung Ha; Ryu, Young Hoon; Lee, Myung Sik; Lyoo, Chul Hyoung
Accumulation of cortical and subcortical tau pathology is the primary pathological substrate for progressive supranuclear palsy (PSP). (18) F-AV-1451, a radiotracer that binds to the pathological tau protein, may be helpful for in vivo visualization and quantitation of tau pathology in PSP. The objectives of this study were to investigate cortical and subcortical (18) F-AV-1451 binding patterns in patients with PSP. We recruited 14 PSP patients and compared their cortical and subcortical binding patterns in (18) F-AV-1451 positron emission tomography (PET) studies with those of 15 Parkinson's disease (PD) patients and 15 healthy controls. In both the PD and PSP groups, subcortical (18) F-AV-1451 binding did not correlate with the severity of motor dysfunctions, and cortical binding did not differ between the controls and each patient group. However, the PSP patients showed greater (18) F-AV-1451 binding in the putamen, globus pallidus, subthalamic nucleus, and dentate nucleus when compared with the controls, whereas the PD patients showed lower (18) F-AV-1451 binding in the substantia nigra than controls. The PSP and PD patients showed distinct subcortical (18) F-AV-1451 binding patterns reflecting subcortical tau pathology in PSP and reduced nigral neuromelanin in PD. However, there was no correlation with the severity of motor dysfunction, no cortical regions with increased binding in PSP patients, and variable degrees of subcortical binding even in the controls. Therefore, the (18) F-AV-1451 PET may be less than ideal for assessing tau pathology in PSP. Further studies will be required to validate the clinical correlation and to understand the clinical utility of (18) F-AV-1451 PET for PSP patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.
Tarazi, Apameh; Tator, Charles H; Tartaglia, Maria Carmela
Association of repetitive brain trauma with progressive neurological deterioration has been described since the 1920s. Punch drunk syndrome and dementia pugilistica (DP) were introduced first to explain symptoms in boxers, and more recently, chronic traumatic encephalopathy (CTE) has been used to describe a neurodegenerative disease in athletes and military personal with a history of multiple concussions. Although there are many similarities between DP and CTE, a number of key differences are apparent especially when comparing movement impairments. The aim of this review is to compare clinical and pathological aspects of DP and CTE with a focus on disorders of movement.
Iacono, Diego; Shively, Sharon B; Edlow, Brian L; Perl, Daniel P
Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated. Published by Elsevier Inc.
Kubat, Bela; Bilo, Rob A C; van Rijn, Rick R
The proof of abusive head trauma (AHT) in infants is difficult, especially in cases with a long posttraumatic survival period. In the acute phase, injury to the cranio-cervical junction causes disturbances in respiratory and cardiac control, leading to apnea and bradycardia. Infants who survive the acute phase may subsequently develop multicystic encephalopathy. Because some types of changes are age-dependent, examination of the patterns of brain damage in these cases could provide information about the time in which they were inflicted. In particular, this could apply to the extent of the cystic changes, namely that the severity thereof may decrease with older age upon infliction of the trauma. This could potentially date the injury and thereby help to identify the perpetrator. We present an analysis of the patterns of brain damage in cases of AHT-induced multicystic encephalopathy and comment on the possible etiology and the implications thereof. Nine archival cases of trauma-induced multicystic encephalopathy, originating between the years 2005 and 2011, were identified. In 8 of these cases, hematoxilin-eosin-stained whole-hemisphere histologic slides, as well as small histologic slides of cerebellar hemispheres, were available for the evaluation of the topographic distribution of the macroscopic and microscopic changes. The cerebral hemispheres were more affected than the cerebellum. The magnitude of the cystic changes did not correlate with the age at which the trauma had occurred, nor the surviva period. All cases showed asymmetrical affection of the cerebral hemispheres, which in 3 cases was very pronounced. The analysis revealed both ischemia- and hypoperfusion-induced injury patterns. Analysis of the magnitude and the distribution of the damage do not assist in the estimation of the period at which the trauma had occurred. The evaluation showed that ischemia, and to a lesser extent, hypoperfusion, were the major mechanisms of brain injury in these cases
Gauthier, Angela C; Baehring, Joachim M
Hashimoto's encephalopathy is a rare, imprecisely defined autoimmune neurologic syndrome associated with Hashimoto's thyroiditis that normally responds to corticosteroids. Here, we describe the case of a 55-year-old woman who presented with subacute cognitive decline and ataxia. Neoplastic, paraneoplastic, infectious, and metabolic etiologies were ruled out. Anti-TPO antibody level was markedly elevated at 966U/mL. After one month of 60mg/day of oral prednisone, she felt back to baseline and her Montreal Cognitive Assessment dramatically improved. Physicians should strongly consider this uncommon diagnosis in patients with rapid cognitive decline and no other clear etiology.
Solomon, Gary S; Sills, Allen
Chronic traumatic encephalopathy (CTE) in sports has been known for > 85 years, and has experienced a resurgence of interest over the past decade, both in the media and in the scientific community. However, there appears to be a disconnection between the public's perception of CTE and the currently available scientific data. The cognitive bias known as the "availability cascade" has been suggested as a reason to explain this rift in knowledge. This review summarizes and updates the history of CTE in sports, discusses recent epidemiological and autopsy studies, summarizes the evidence base related to CTE in sports, and offers recommendations for future directions.
Montagnese, Sara; Turco, Matteo; Amodio, Piero
Sleep-wake abnormalities in patients with cirrhosis have been traditionally associated with hepatic encephalopathy (HE). In recent years, a certain amount of work has been devoted to the study of this relationship. This has lead to a modified picture, with weakening of the association between HE and poor night sleep, and the emergence of stronger links between HE and excessive daytime sleepiness. This brief review focuses on the evidence in favor of the interpretation of HE as a sleepiness syndrome, and on the diagnostic, therapeutic and social implications of such an interpretation. PMID:26041958
Buge, A; Supino-Viterbo, V; Rancurel, G; Pontes, C
Seventy patients admitted to hospital with bismuth encephalopathy had repeated clinical and EEG examinations. All the patients exhibited myoclonic jerks, but no paroxysmal features ever appeared on EEG. Computed tomography showed cortical hyperdensities. Seizures were observed in 22 patients, but epileptic EEG patterns appeared only when the bismuth blood level was below 1500 microgram/1. It is suggested that a high cortical intracellular bismuth concentration induces a "cortical inhibition" which causes suppression of physiological electrical brain activity, the absence of EEG paroxysmal phenomena during myoclonic jerks, and explains the rarity of epileptic seizures. Images PMID:7205307
Anselmo, Marisol; Campos Rainho, António; do Carmo Vale, Maria; Estrada, João; Valente, Rosalina; Correia, Manuela; Vieira, José Pedro; Barata, Deolinda
Methadone is used in the treatment of opioid addiction. Acute intoxication can lead to severe consequences and can even be lethal. In several case reports and small series, a presumably toxic leukoencephalopathy is described resulting from inhalation of heroin. We present the case of a 3-year-old boy who ingested methadone accidentally. In a coma with acute obstructive hydrocephalus owing to massive cerebellar edema and supratentorial lesions, he was successfully treated with methylprednisolone and cerebrospinal fluid external drainage. To our knowledge, this is the first report of an encephalopathy associated with synthetic opioid intoxication.
Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D
Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.
McKee, Ann C; Alosco, Michael L; Huber, Bertrand R
Chronic traumatic encephalopathy (CTE) is a distinctive neurodegenerative disease that occurs as a result of repetitive head impacts. CTE can only be diagnosed by postmortem neuropathologic examination of brain tissue. CTE is a unique disorder with a pathognomonic lesion that can be reliably distinguished from other neurodegenerative diseases. CTE is associated with violent behaviors, explosivity, loss of control, depression, suicide, memory loss and cognitive changes. There is increasing evidence that CTE affects amateur athletes as well as professional athletes and military veterans. CTE has become a major public health concern.
Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin
Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover
Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran
A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances. PMID:27099774
Zhang, Y; Suga, N
Since 1962, physiological data of corticofugal effects on subcortical auditory neurons have been controversial: inhibitory, excitatory, or both. An inhibitory effect has been much more frequently observed than an excitatory effect. Recent studies performed with an improved experimental design indicate that corticofugal system mediates a highly focused positive feedback to physiologically "matched" subcortical neurons, and widespread lateral inhibition to "unmatched" subcortical neurons, in order to adjust and improve information processing. These results lead to a question: what happens to subcortical auditory responses when the corticofugal system, including matched and unmatched cortical neurons, is functionally eliminated? We temporarily inactivated both matched and unmatched neurons in the primary auditory cortex of the mustached bat with muscimol (an agonist of inhibitory synaptic transmitter) and measured the effect of cortical inactivation on subcortical auditory responses. Cortical inactivation reduced auditory responses in the medial geniculate body and the inferior colliculus. This reduction was larger (60 vs. 34%) and faster (11 vs. 31 min) for thalamic neurons than for collicular neurons. Our data indicate that the corticofugal system amplifies collicular auditory responses by 1.5 times and thalamic responses by 2.5 times on average. The data are consistant with a scheme in which positive feedback from the auditory cortex is modulated by inhibition that may mostly take place in the cortex.
Sacchet, Matthew D; Livermore, Emily E; Iglesias, Juan Eugenio; Glover, Gary H; Gotlib, Ian H
Subcortical gray matter regions have been implicated in mood disorders, including Major Depressive Disorder (MDD) and Bipolar Disorder (BD). It is unclear, however, whether or how these regions differ among mood disorders and whether such abnormalities are state- or trait-like. In this study, we examined differences in subcortical gray matter volumes among euthymic BD, MDD, remitted MDD (RMD), and healthy (CTL) individuals. Using automated gray matter segmentation of T1-weighted MRI images, we estimated volumes of 16 major subcortical gray matter structures in 40 BD, 57 MDD, 35 RMD, and 61 CTL individuals. We used multivariate analysis of variance to examine group differences in these structures, and support vector machines (SVMs) to assess individual-by-individual classification. Analyses yielded significant group differences for caudate (p = 0.029) and ventral diencephalon (VD) volumes (p = 0.003). For the caudate, both the BD (p = 0.004) and the MDD (p = 0.037) participants had smaller volumes than did the CTL participants. For the VD, the MDD participants had larger volumes than did the BD and CTL participants (ps < 0.005). SVM distinguished MDD from BD with 59.5% accuracy. These findings indicate that mood disorders are characterized by anomalies in subcortical gray matter volumes and that the caudate and VD contribute uniquely to differential affective pathology. Identifying abnormalities in subcortical gray matter may prove useful for the prevention, diagnosis, and treatment of mood disorders.
Li, Xiaobo; Black, Margaret; Xia, Shugao; Zhan, Chenyang; Bertisch, Hilary C; Branch, Craig A; DeLisi, Lynn E
Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.
Hou, Li J.; Song, Zheng; Pan, Zhu J.; Cheng, Jia L.; Yu, Yong; Wang, Jun
One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264
Wu, Xiujuan; Wu, Wei; Pan, Wei; Wu, Limin; Liu, Kangding; Zhang, Hong-Liang
Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease. PMID:25873770
Maki, Yoshimitsu; Takashima, Hiroshi
Hashimoto encephalopathy (HE) is characterized by heterogeneous neurological symptoms. HE is diagnosed based on three criteria-the presence of antithyroid antibodies, neurological symptoms from the cerebrum and/or cerebellum, and a positive response to immunotherapy. We clinically analyzed 18 patients (3 men, 15 women; age range, 38-81years) diagnosed with HE in our hospital from May 2013 to January 2016. Eleven patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or neuralgia. Surprisingly, the majority of the pain was distributed in a manner that was not explainable anatomically. Seventeen patients showed motor disturbances, such as weakness, paresis of extremities, or dexterity movement disorder, and eight patients showed give-way weakness, which is disruption of continuous muscle contraction. Other symptoms indicative of brain-related anomalies such as tremor, dystonia, involuntary movements, cerebellar ataxia, parkinsonism, memory loss, and chronic fatigue were also seen. In most patients, such motor, sensory, or higher brain functions were markedly improved with immunosuppressive therapies such as prednisolone, azathioprine, or immunoadsorption therapy. Although give-way weakness and anatomically unexplainable pain are typically considered as being psychogenic in origin, the presence of these symptoms is indicative of HE. HE exhibits diffuse involvement of the entire brain and thus, these symptoms are explainable. We propose that physicians should not diagnose somatoform disorders without first excluding autoimmune encephalopathy.
Bigatello, L M; Broitman, S A; Fattori, L; Di Paoli, M; Pontello, M; Bevilacqua, G; Nespoli, A
Endotoxemia without sepsis was detected with a chromogenic Limulus assay in 36 of 39 (92.3%) cirrhotic patients and was absent in seven healthy volunteers. In 11 patients who underwent elective portasystemic shunt, portal vein endotoxemia was higher than inferior vena caval: p less than 0.05, systemic endotoxin levels did not change, compared to preoperative levels, on the 1st, 2nd, and 3rd postoperative days, attendant to an uneventful recovery. In 21 patients in hepatic encephalopathy after esophagogastric hemorrhage, systemic endotoxemia was higher than in well-compensated cirrhotics: p less than 0.001; it was higher in deep than in light coma: p less than 0.05; it was higher in those who died than in those who survived: p less than 0.001. Endotoxin levels showed a positive correlation with serum bilirubin: r = 0.59, p less than 0.001, and a negative correlation with prothrombin activity: r = -0.59, p less than 0.001. These data show endotoxemia without sepsis is a constant finding in cirrhosis and increasing levels of endotoxemia are associated with hepatic failure, encephalopathy, and death.
Butterworth, Roger F
It is generally assumed that neuronal cell death is minimal in liver failure and is insufficient to account for the neuropsychiatric symptoms characteristic of hepatic encephalopathy. However, contrary to this assumption, neuronal cell damage and death are well documented in liver failure patients, taking the form of several distinct clinical entities namely acquired (non-Wilsonian) hepatocerebral degeneration, cirrhosis-related Parkinsonism, post-shunt myelopathy and cerebellar degeneration. In addition, there is evidence to suggest that liver failure contributes to the severity of neuronal loss in Wernicke's encephalopathy. The long-standing nature of the thalamic and cerebellar lesions, over 80% of which are missed by routine clinical evaluation, together with the probability that they are nutritional in origin, underscores the need for careful nutritional management (adequate dietary protein, Vitamin B(1)) in liver failure patients. Mechanisms identified with the potential to cause neuronal cell death in liver failure include NMDA receptor-mediated excitotoxicity, lactic acidosis, oxidative/nitrosative stress and the presence of pro-inflammatory cytokines. The extent of neuronal damage in liver failure may be attenuated by compensatory mechanisms that include down-regulation of NMDA receptors, hypothermia and the presence of neuroprotective steroids such as allopregnanolone. These findings suggest that some of the purported "sequelae" of liver transplantation (gait ataxia, memory loss, confusion) could reflect preexisting neuropathology.
Daneshvar, Daniel H.; Baugh, Christine M.; Seichepine, Daniel R.; Montenigro, Philip H.; Riley, David O.; Fritts, Nathan G.; Stamm, Julie M.; Robbins, Clifford A.; McHale, Lisa; Simkin, Irene; Stein, Thor D.; Alvarez, Victor E.; Goldstein, Lee E.; Budson, Andrew E.; Kowall, Neil W.; Nowinski, Christopher J.; Cantu, Robert C.; McKee, Ann C.
Objective: The goal of this study was to examine the clinical presentation of chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases. Methods: Thirty-six adult male subjects were selected from all cases of neuropathologically confirmed CTE at the Boston University Center for the Study of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no comorbid neurodegenerative or motor neuron disease, and had next-of-kin informants to provide retrospective reports of the subjects' histories and clinical presentations. These interviews were conducted blind to the subjects' neuropathologic findings. Results: A triad of cognitive, behavioral, and mood impairments was common overall, with cognitive deficits reported for almost all subjects. Three subjects were asymptomatic at the time of death. Consistent with earlier case reports of boxers, 2 relatively distinct clinical presentations emerged, with one group whose initial features developed at a younger age and involved behavioral and/or mood disturbance (n = 22), and another group whose initial presentation developed at an older age and involved cognitive impairment (n = 11). Conclusions: This suggests there are 2 major clinical presentations of CTE, one a behavior/mood variant and the other a cognitive variant. PMID:23966253
Liou, Kuang-Chung; Kuo, Shu-Fan; Chen, Lu-An
Wernicke encephalopathy (WE) is a medical emergency caused by thiamine (vitamin B1) deficiency. Typical clinical manifestations are mental change, ataxia, and ocular abnormalities. Wernicke encephalopathy is an important differential diagnosis in all patients with acute mental change. However, the disorder is greatly underdiagnosed. Clinical suspicion, detailed history taking, and neurologic evaluations are important for early diagnosis. Magnetic resonance imaging (MRI) is currently considered the diagnostic method of choice. Typical MRI findings of WE are symmetrical involvement of medial thalamus, mammillary body, and periaqueductal gray matter. Prompt thiamine supplement is important in avoiding unfavorable outcomes. Here, we report a case of alcoholic WE with typical clinical presentation but with atypical MRI. Axial fluid-attenuated inversion recovery images showing symmetrical hyperintensity lesions in dentate nuclei of cerebellum, olivary bodies, and dorsal pons. Although atypical MRI findings are more common in nonalcoholic WE, it can also occur in alcoholic WE. This article is aimed to highlight the potential pitfalls in diagnosing acute mental change, the importance of clinical suspicion, and early treatment in WE.
Lipman, J.J.; Colowick, S.P.; Lawrence, P.P.; Abumrad, N.N.
Aluminum tartrate (AlT) but not sodium tartrate (NaT) produces a progressive encephalopathy when injected intracerebroventricularly in the rat. This syndrome, lethal within 30-35 days, is characterized by progressively deranged behavior. An early startle reaction, later joined by locomotor discoordination is followed by locomotor and electrocorticographic (ECoG) seizures in chronically instrumented AlT rats. There is early dissociation between ECoG and locomotor aspects. When tested in the shuttlebox for estimation of learning and memory function 7-8 days after AlT injection, marked impairment of both active and passive avoidance was observed. Glucose uptake capacity of synaptosomes from brain areas of AlT and NaT animals was indexed by the 2-deoxy-D-glucose method. Striatal and cortical synaptosomes showed reduced uptake activity 7 days following Alt injection. By day 14, hypothalamic areas also became affected, striatal uptake was further inhibited, and cortical uptake was reduced to 57% of control. The ECoG background rhythm remained unchanged until days 20-23, when the mean peak frequency was reduced. The model may be useful in the study of central aluminum toxicity and may have predictive validity in the testing of procedures to counter aluminum-associated encephalopathies in man. 44 references, 4 figures, 1 table.
Walsh, Brian H; Neil, Jeffrey; Morey, JoAnn; Yang, Edward; Silvera, Michelle V; Inder, Terrie E; Ortinau, Cynthia
To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia. This retrospective cohort studied infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia at a single tertiary neonatal intensive care unit between 2013 and 2015. Two neuroradiologists masked to the clinical condition evaluated brain MRIs for cerebral injury after therapeutic hypothermia using the Barkovich classification system. Additional abnormalities not included in this classification system were also noted. The rate, pattern, and severity of abnormalities/injury were compared across the grades of neonatal encephalopathy. Eighty-nine infants received therapeutic hypothermia and met study criteria, 48 with mild neonatal encephalopathy, 35 with moderate neonatal encephalopathy, and 6 with severe neonatal encephalopathy. Forty-eight infants (54%) had an abnormality on MRI. There was no difference in the rate of overall MRI abnormalities by grade of neonatal encephalopathy (mild neonatal encephalopathy 54%, moderate neonatal encephalopathy 54%, and severe neonatal encephalopathy 50%; P= .89). Basal ganglia/thalamic injury was more common in those with severe neonatal encephalopathy (mild neonatal encephalopathy 4%, moderate neonatal encephalopathy 9%, severe neonatal encephalopathy 34%; P = .03). In contrast, watershed injury did not differ between neonatal encephalopathy grades (mild neonatal encephalopathy 36%, moderate neonatal encephalopathy 32%, severe neonatal encephalopathy 50%; P = .3). Mild neonatal encephalopathy is commonly associated with MRI abnormalities after therapeutic hypothermia. The grade of neonatal encephalopathy during the first hours of life may not discriminate adequately between infants with and without cerebral injury noted on MRI after therapeutic hypothermia
Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie
We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.
Stawicka, Agnieszka; Zbrzeźniak, Justyna; Świderska, Aleksandra; Kilisińska, Natalia; Świderska, Magdalena; Jaroszewicz, Jerzy; Flisiak, Robert
Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods.
Hypertensive encephalopathy with the clinicoradiological entity posterior reversible encephalopathy syndrome in the setting of venlafaxine as single therapy has not been reported earlier. A 46-year-old man developed hypertensive encephalopathy associated with venlafaxine as single therapy. Magnetic resonance imaging of the brain, pre and post gadolinium, carried out on day 2, displayed an increased T2 signal in the cortex on both the T2 and FLAIR images throughout the frontal and temporal lobes and in the cerebellum. Venlafaxine therapy was stopped. The patient gradually improved and he became seizure free and the blood pressure successively became normal. A magnetic resonance imaging after six weeks displayed marked regression of the abnormalities. On follow-up after 3 months, his blood pressure had been normal and he had not had any symptoms. The prescribed antiepileptic drug was discontinued as well as antihypertensive treatment. He had not experienced any new symptoms at follow-up after one year. The patient in this report had hypertensive encephalopathy associated with venlafaxine therapy. The imaging findings are compatible with hypertensive encephalopathy/posterior reversible encephalopathy syndrome. Venlafaxine is a drug used very frequently. Venlafaxine may infrequently induce hypertensive crisis. Hypertensive encephalopathy may rarely occur in the setting of venlafaxine as single therapy even in low to moderate doses. Patients on venlafaxine should have regular monitoring of blood pressure. Knowledge of the side effects is vital. Venlafaxine must be discontinued if significant hypertension persists.
Yun, Byung Cheol; Kim, W Ray
Hyponatremia, a common complication inpatients with advanced liver disease and impaired free water clearance, has been shown to be an important predictor of short-term mortality. Hepatic encephalopathy, also a late complication of end-stage liver disease, has been associated with low-grade cerebral edema as a result of swelling of astrocytes. Guevara et al. hypothesized that hyponatremia and the resultant depletion of organic osmolytes (e.g.,myo-inositol) from brain cells contribute to brain edema, playing an important role in the pathogenesis of hepatic encephalopathy. Using a multivariable analysis, they demonstrated that hyponatremia increased the risk of hepatic encephalopathy more than eightfold, after adjustment for serum bilirubin and creatinine concentrations and previous history of encephalopathy. Their magnetic resonance spectroscopy data correlated low brain concentrations of myoinositol with hepatic encephalopathy. As both hyponatremia and encephalopathy occur in patients with advanced liver disease, it has been difficult to implicate hyponatremia independently in the pathogenesis of hepatic encephalopathy. Guevara's data do suggest that hyponatremia is more likely an accomplice than an innocent bystander.
Matsuo, Muneaki; Maeda, Toshiyuki; Ono, Nobuyasu; Sugihara, Susumu; Kobayashi, Ikuko; Koga, Daisuke; Hamasaki, Yuhei
Acute encephalopathy with biphasic seizures and late reduced diffusion was recently established clinicoradiologically as an encephalopathy syndrome. The outcome of this encephalopathy is characterized by a low mortality rate and high incidence of neurologic sequelae. Although the exact pathogenesis of this encephalopathy is uncertain, excitotoxic injury with delayed neuronal death is proposed. On the basis of this hypothesis, we tried a combination therapy of N-methyl-D-aspartate receptor antagonist, dextromethorphan, and apoptosis inhibitor, cyclosporine A, in four patients with acute encephalopathy with biphasic seizures and late reduced diffusion. All patients recovered except for hyperactivity in one patient. Furthermore, an additional four patients with near-miss encephalopathy, who showed mild disturbance of consciousness at 24 hours after prolonged febrile seizures associated with exanthem subitum, recovered without secondary seizures by the early administration of dextromethorphan. The combination regimen of dextromethorphan and cyclosporine A could be effective for the treatment and prevention of acute encephalopathy with biphasic seizures and late reduced diffusion. Copyright © 2013 Elsevier Inc. All rights reserved.
Oliver, Karen L.; Lukic, Vesna; Thorne, Natalie P.; Berkovic, Samuel F.; Scheffer, Ingrid E.; Bahlo, Melanie
We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets. PMID:25014031
Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong
Abstract Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice. A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1. To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians’ awareness of its possible onset. PMID:27399058
Blom, H J; Ferenci, P; Grimm, G; Yap, S H; Tangerman, A
Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant. In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy.
Suh, Hyee; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon
The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia. PMID:23342322
Weiss, Michael W; Bidelman, Gavin M
Auditory experiences including musicianship and bilingualism have been shown to enhance subcortical speech encoding operating below conscious awareness. Yet, the behavioral consequence of such enhanced subcortical auditory processing remains undetermined. Exploiting their remarkable fidelity, we examined the intelligibility of auditory playbacks (i.e., "sonifications") of brainstem potentials recorded in human listeners. We found naive listeners' behavioral classification of sonifications was faster and more categorical when evaluating brain responses recorded in individuals with extensive musical training versus those recorded in nonmusicians. These results reveal stronger behaviorally relevant speech cues in musicians' neural representations and demonstrate causal evidence that superior subcortical processing creates a more comprehensible speech signal (i.e., to naive listeners). We infer that neural sonifications of speech-evoked brainstem responses could be used in the early detection of speech-language impairments due to neurodegenerative disorders, or in objectively measuring individual differences in speech reception solely by listening to individuals' brain activity.
Suh, Hyee; Shin, Yong-Il; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon
The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.
Elwir, Saleh; Rahimi, Robert S.
Abstract Hepatic encephalopathy is a spectrum of reversible neuropsychiatric abnormalities, seen in patients with liver dysfunction and/or portosystemic shunting. One of the most debilitating complications of cirrhosis, encephalopathy affects 30–45% of cirrhotics. In addition to significantly affecting the lives of patients and their caregivers, it is also associated with increased morbidity and mortality as well as significant utilization of health care resources. In this paper, we provide an overview on the pathophysiology, diagnosis, management and newer therapies of hepatic encephalopathy. PMID:28660152
Vierling, John M
Both covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE) impair the ability to operate machinery. The legal responsibilities of US physicians who diagnose and treat patients with hepatic encephalopathy vary among states. It is imperative that physicians know the laws regarding reporting in their state. OHE represents a neuropsychiatric impairment that meets general reporting criteria. The medical advisory boards of the states have not identified OHE as a reportable condition. In the absence of validated diagnostic guidelines, physicians are not obligated to perform tests for CHE. There is a need for explicit guidance from professional associations regarding this issue.
Osman, Y; Imam, Y Z; Salem, K; Al-Hail, H; Uthman, B; Deleu, D
Hypertensive encephalopathy typically presents with headache, confusion, and bilateral parietooccipital vasogenic edema. Brainstem edema in hypertensive encephalopathy usually occurs in association with typical supratentorial parieto-occipital changes and is usually asymptomatic. We report here a patient with hypertensive encephalopathy, with isolated brain stem involvement on magnetic resonance imaging (MRI). Rapid treatment of hypertension resulted in clinical and radiological improvement. Prompt recognition of the condition and aggressive treatment of hypertension in such patients is crucial to relieve edema and prevent life-threatening progression.
Choi, Jay Chol; Kang, Ji-Hoon
Hypertensive encephalopathy is a medical emergency whose clinical manifestations are usually associated with bilateral parieto-occipital lesions. Predominant brainstem edema without accompanying occipital lesions is rare in hypertensive encephalopathy and usually occurs in patients with secondary hypertension. We describe the clinical and radiological features of two patients with reversible hypertensive brainstem encephalopathy. Both patients had chronic renal failure, but the extensive neuroimaging abnormalities revealed few clinical features of brainstem involvement. The clinical findings and neuroimaging abnormalities resolved once the hypertension was treated. PMID:19513343
Ramcharan, Kanterpersad; Hosein, Nadeem; Teelucksingh, Joel David; Rampersad, Fidel; Teelucksingh, Surujpal
Hashimoto's encephalopathy often presents with neuropsychiatric manifestations including seizures and movement disorders. We describe a patient who presented with bilateral hand tremor and mild cognitive defects that fulfilled the criteria for a diagnosis of Hashimoto's encephalopathy. There was a rapid response to glucocorticoid therapy with relapse following treatment withdrawal. Recently published clinical criteria for the diagnosis of Hashimoto's encephalopathy include seizures, myoclonus, hallucinations, or stroke-like episodes but do not include tremor. Our case had mild cognitive dysfunction and a coarse tremor as the predominant clinical features, which probably represent mild disease.
Papetti, Laura; Garone, Giacomo; Schettini, Livia; Giordano, Carla; Nicita, Francesco; Papoff, Paola; Zeviani, Massimo; Leuzzi, Vincenzo; Spalice, Alberto
Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome.
Reardon, Paul Kirkpatrick; Clasen, Liv; Giedd, Jay N; Blumenthal, Jonathan; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin
Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. Copyright © 2016 the authors 0270-6474/16/362438-11$15.00/0.
McFadyen, Jessica; Mermillod, Martial; Mattingley, Jason B; Halász, Veronika; Garrido, Marta I
There is significant controversy over the existence and function of a direct subcortical visual pathway to the amygdala. It is thought that this pathway rapidly transmits low spatial frequency information to the amygdala independently of the cortex and yet the directionality of this function has never been determined. We used magnetoencephalography to measure neural activity while human participants discriminated the gender of neutral and fearful faces filtered for low or high spatial frequencies. We applied dynamic causal modelling to demonstrate that the most likely underlying neural network consisted of a pulvinar-amygdala connection that was uninfluenced by spatial frequency or emotion, and a cortical-amygdala connection that conveyed high spatial frequencies. Crucially, data-driven neural simulations revealed a clear temporal advantage of the subcortical connection over the cortical connection in influencing amygdala activity. Thus, our findings support the existence of a rapid subcortical pathway that is non-selective in terms of the spatial frequency or emotional content of faces. We propose that that the 'coarseness' of the subcortical route may be better reframed as 'generalised'.SIGNIFICANCE STATEMENTThe human amygdala co-ordinates how we respond to biologically relevant stimuli, such as threat or reward. It has been postulated that the amygdala first receives visual input via a rapid subcortical route that conveys 'coarse' information, namely low spatial frequencies. For the first time, the present paper provides direction-specific evidence from computational modelling that the subcortical route plays a generalised role in visual processing by rapidly transmitting raw, unfiltered information directly to the amygdala. This calls into question a widely held assumption across human and animal research that fear responses are produced faster by low spatial frequencies. Our proposed mechanism suggests organisms quickly generate fear responses to a wide range
Gandhi, Kamal J K; Gilmore, Daniel W; Haack, Robert A; Katovich, Steven A; Krauth, Steven J; Mattson, William J; Zasada, John C; Seybold, Steven J
From 2000 through 2003 we used semiochemical-baited traps in northeastern Minnesota, USA, to assess changes in assemblages of subcortical forest insects after a catastrophic wind storm in 1999 and subsequent (1999-2000) fuel-reduction activities (salvage-logging and prescribed-burning). We determined the regional efficacy of fifteen semiochemical blends (pheromones and kairomones) as attractants for target and non-target subcortical insect species (Coleoptera: Anthribidae, Buprestidae, Cerambycidae, Cleridae, Cucujidae, Curculionidae, Histeridae, Nemonychidae, Salpingidae, Scolytidae, Tenebrionidae, and Hymenoptera: Siricidae). During the four summers, we trapped 86,471 subcortical insects (143 species) in baited and unbaited Lindgren funnel traps, and 500 beetles (44 species) in baited and unbaited pitfall traps. We report 23 new state collection records of subcortical insects from Minnesota. Trap catches of subcortical insects were greatest in the wind-disturbed areas 2 years after the event, and declined thereafter. Similar trends were observed for subcortical insects in the burned areas. Both wind-disturbance and burning increased the subcortical insect species richness and diversity on the landscape. The subcortical insect species compositions of the salvaged and burned forest areas differed from those of the undisturbed and wind-disturbed areas. Trap catches of subcortical insects in response to semiochemical treatments also varied with year of sampling and land-area treatment. The greatest diversity of subcortical beetle species was in traps baited with attractants for the scolytids, Dendroctonus valens [(+)-α-pinene and (−)-β-pinene] and Dryocoetes spp. [exo-brevicomin and (−)-α-pinene], perhaps reflecting the generic nature of the baits. The most distinct species compositions were collected in response to the woodborer and Dendroctonus simplex baits, whereas the species compositions in traps with the D. valens and Dryocoetes spp. baits, and the
Basu, P Patrick; Shah, Niraj James
Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric manifestations. A combined effort with neuropsychological and psychometric evaluation has to be performed to recognize the syndrome, whereas minimal HE (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed through specialized neuropsychiatric testing. Early diagnosis and treatment may drastically improve the quality of life for many cirrhotic patients. Further research to gain better insight into the pathophysiology and diagnostic accuracy of HE will help determine future management strategies.
Riley, David O; Robbins, Clifford A; Cantu, Robert C; Stern, Robert A
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease associated with repetitive brain trauma (RBT). Initially described in boxers, CTE has now been found in other contact sport athletes with a history of RBT. In recent years, there has been tremendous media attention regarding CTE, primarily because of the deaths of high profile American football players who were found to have CTE upon neuropathological examination. However, the study of CTE remains in its infancy. This review focuses on research from the Centre for the Study of Traumatic Encephalopathy (CSTE) at Boston University. This study reviews the formation of the CSTE, major CSTE publications and current ongoing research projects at the CSTE. The neuropathology of CTE has been well-described. Current research focuses on: methods of diagnosing the disease during life (including the development of biomarkers), examination of CTE risk factors (including genetic susceptibility and head impact exposure variables); description of the clinical presentation of CTE; development of research diagnostic criteria for Traumatic Encephalopathy Syndrome; and assessment of mechanism and pathogenesis. Current research at the BU CSTE is aimed at increasing understanding of the long-term consequences of repetitive head impacts and attempting to begin to answer several of the unanswered questions regarding CTE.
Jiménez-Peña, M M; Gil-Robles, S; Cano-Alonso, R; Recio-Rodríguez, M; Carrascoso-Arranz, J; Ruiz-Ocaña, C; Martínez-Vega, V
Diffusion tensor imaging (DTI) and tractography provide the neurosurgeon with a valid 3D view of the white matter tracts of the brain for the presurgical planning of the treatment of lesions close to eloquent areas, this being one of the principal clinical applications of this technique. In this article, we describe through practical cases the anatomic relationships of white matter tracts that are essential for language and reading, based on DTI studies and the excellent anatomic correlation with the intraoperative subcortical map.
Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray
Hepatic encephalopathy (HE) develops in up to 50% of patients with cirrhosis and is a feature of decompensated cirrhosis. With the goal of reviewing the evidence for treatment and prevention of overt hepatic encephalopathy, pubmed was searched using search terms hepatic encephalopathy AND treatment, limited to human studies from January 1, 2003, through December 1, 2013, and supplemented by key references. The inpatient incidence of HE is approximately 23,000 annually, and management of these patients is common for internists and subspecialists. Treatment of the hospitalized patient with HE has changed in recent years. Treatment entails 2 phases: induction and maintenance of remission. Most cases of significant HE are precipitated by infection, gastrointestinal bleeding, medications, or other culprits. All patients should be evaluated for secondary triggers of HE, and treatment should be initiated with a nonabsorbable disaccharide (ie, lactulose) in most patients. Rifaximin (off label) can be added in patients not responding to lactulose. Neomycin is a less preferred alternative to rifaximin owing to its adverse effect profile. Other therapies, including zinc, L-ornithine-L-aspartate, and branched-chain amino acids, can be considered for patients not responding to disaccharides and nonabsorbable antibiotics. Large portosystemic shunts may be embolized in patients with medically refractory recurrent or severe HE with otherwise well-compensated cirrhosis. Molecular Adsorbent Recirculating System is now available for patients with severe HE who do not respond to medical therapy. It is critically important that patients hospitalized with significant HE continue maintenance therapy at the time of dismissal to prevent further episodes. Patients with a first-time episode of HE can be administered lactulose, and careful instructions should be provided to patients and caregivers about dose titration to achieve 3 bowel movements daily. Patients with recurrent HE episodes
Tian, X J; Zhang, Y H; Liu, A J; Yang, X L; Zeng, Q; Yang, Z X; Ye, J T; Liu, X Y; Jiang, Y W; Wu, X R
Objective: To investigate the clinical and neuroimaging characteristics of acute encephalopathy (AE) after status epilepticus (SE) of patients with Dravet syndrome (DS). Method: The clinical data of DS patients who had AE (coma ≥24 h) after SE were retrospectively collected from February 2005 to August 2016 in Peking University First Hospital and SCN1A gene tests were performed.The clinical and neuroimaging features were summarized. Result: Twenty-two patients (9 males and 13 females) with AE were collected among 412 DS patients during follow-up.Of which 18 patients had SCN1A gene mutations while the remaining 4 patients had no SCN1A gene mutations.The onset age of AE was between 6 months and 10 years.The duration of SE varied between 40 minutes and 9 hours.Prior to the onset of SE, twenty-one patients had high fever, and one patient had normal temperature.Coma lasted from 2 days to 20 days.Nine patients died after the AE, and 13 patients survived with massive neurological regression.From AE to the last visit, the median time of follow-up was 2 years and 3 months (from 7 months to 4 years and 4 months). Nine of 13 survivors had varied improvement in motor, language and cognition, while the remaining 4 patients had no significant improvement.After AE, there were 6 patients with seizure-free, 4 patients with reduced seizures, and 3 patients with no change in seizure frequency, moreover, spasm occurred in 2 patients.Six patients had brain magnetic resonance imaging (MRI) in acute phase and showed bilateral (2 patients) or unilateral (4 patients) hemisphere edema, accompanied by subcortical white matter hyperintense signal in T1 and T2 weighted images in two patients.The neuroimaging of 13 survivors demonstrated diverse cortical atrophy during recovery phase, among which 4 patients showed cerebellar atrophy, one patient had right pontine atrophy, 4 patients accompanied by signal abnormalities in subcortical and periventricular white matter, 2 patients showed right
Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S
Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.
Ong, Chin-Sing; McConnell, James R.; Chu, Wei-Kom
Liver failure can induce gradations of encephalopathy from mild to stupor to deep coma. The objective of this study is to investigate and quantify the variation of biochemical compounds in the brain in patients with liver failure and encephalopathy, through the use of water- suppressed, localized in-vivo Proton Magnetic Resonance Spectroscopy (HMRS). The spectral parameters of the compounds quantitated are: N-Acetyl Aspartate (NAA) to Creatine (Cr) ratio, Choline (Cho) to Creatine ratio, Inositol (Ins) to Creatine ratio and Glutamine-Glutamate Amino Acid (AA) to Creatine ratio. The study group consisted of twelve patients with proven advanced chronic liver failure and symptoms of encephalopathy. Comparison has been done with results obtained from five normal subjects without any evidence of encephalopathy or liver diseases.
Baev, V M; Kozlov, D B
Acute hypertensive encephalopathy in elderly patients appears reversible mild cognitive impairment. The erythrocyte sedimentation rate and blood creatinine measured during a hypertensive crisis are predictors of decline of visual-spatial orientation after two weeks of treatment.
... related severe neonatal encephalopathy have severe to profound intellectual disability. Affected males have breathing problems, with some having ... syndrome , which has signs and symptoms that include intellectual disability, seizures, and movement problems. In some cases, males ...
Novy, Jan; Catarino, Claudia B; Chinthapalli, Krishna; Smith, Shelagh M; Clayton-Smith, Jill; Hennekam, Raoul C M; Hammond, Peter; Sisodiya, Sanjay M
Dravet syndrome has been found recently as an important underlying condition in cases of alleged vaccine encephalopathy after pertussis vaccination, where vaccination seemed to have precipitated the occurrence of the disease without modifying the long-term course. We report on a patient diagnosed with Angelman syndrome in her fifth decade, in whom the intellectual disability and epilepsy had been assumed to be caused by a vaccine encephalopathy following smallpox vaccination. Clinical features of Angelman syndrome had faded away. The history of the present patient suggests that genetic conditions other than Dravet syndrome can be associated with an alleged vaccine encephalopathy. A history of vaccine encephalopathy is rare among patients with learning disability and refractory epilepsy (1.4% in our cohort), but it should lead to consideration of a comprehensive genetic work-up if Dravet syndrome is excluded. The early history of the patient, when available, should guide the investigations. Medico-legal aspects are also discussed.
Seifter, Julian Lawrence; Samuels, Martin A
Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekbom's syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed. © Thieme Medical Publishers.
Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira
The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.
Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A
Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconvulsive status epilepticus remains unknown, this disorder is thought to lead to neuronal damage, so its identification and treatment are important. Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status. We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status. He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.
Galgano, Michael A; Cantu, Robert; Chin, Lawrence S
Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE.
Chronic traumatic encephalopathy (CTE) has received widespread media attention and is treated in the lay press as an established disease, characterized by suicidality and progressive dementia. The extant literature on CTE is reviewed here. There currently are no controlled epidemiological data to suggest that retired athletes are at increased risk for dementia or that they exhibit any type of unique neuropathology. There remain no established clinical or pathological criteria for diagnosing CTE. Despite claims that CTE occurs frequently in retired National Football League (NFL) players, recent studies of NFL retirees report that they have an all-cause mortality rate that is approximately half of the expected rate, and even lower suicide rates. In addition, recent clinical studies of samples of cognitively impaired NFL retirees have failed to identify any unique clinical syndrome. Until further controlled studies are completed, it appears to be premature to consider CTE a verifiable disease.
Tartaglia, Maria Carmela; Hazrati, Lili-Naz; Davis, Karen D; Green, Robin E A; Wennberg, Richard; Mikulis, David; Ezerins, Leo J; Keightley, Michelle; Tator, Charles
"Chronic traumatic encephalopathy" (CTE) is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this "perspective" is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.
McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.
A primed continuous infusion of (/sup 15/N, 1-/sup 13/C)leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet (0.6 g protein per kg ideal body weight (IBW)). An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO/sub 2/ enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy.
Christopoulou, Foteini; Rizos, Evangelos C; Kosta, Paraskevi; Argyropoulou, Maria I; Elisaf, Moses
A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.
Sheasgreen, Christopher; Lu, Lucy; Patel, Ameen
Hepatic encephalopathy (HE) is a common complication of cirrhosis of the liver. It is also extremely debilitating, with an untreated 3-year survival of only 23 %. While the exact pathophysiology of HE has yet to be elucidated, a number of contributing factors have been described. Abnormal levels and altered metabolism of ammonia play a central role. Recently, inflammation has also been identified as a contributor to HE. Improved understanding of the pathophysiology of HE is crucial, as current therapy centers on reduction of the body's ammonia load. Lactulose is the first-line therapy for HE, with some antibiotics recently showing promise for improved outcomes in patients with HE. The role of anti-inflammatory therapies has yet to be evaluated.
Jacobs, Susan E; Berg, Marie; Hunt, Rod; Tarnow-Mordi, William O; Inder, Terrie E; Davis, Peter G
Newborn animal studies and pilot studies in humans suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae without adverse effects. To determine the effect of therapeutic hypothermia in encephalopathic asphyxiated newborn infants on mortality, long-term neurodevelopmental disability and clinically important side effects. We used the standard search strategy of the Cochrane Neonatal Review Group as outlined in The Cochrane Library (Issue 2, 2007). Randomised controlled trials evaluating therapeutic hypothermia in term and late preterm newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2007, Issue 2), MEDLINE (1966 to June 2007), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal handsearching. We updated this search in May 2012. We included randomised controlled trials comparing the use of therapeutic hypothermia with standard care in encephalopathic term or late preterm infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Four review authors independently selected, assessed the quality of and extracted data from the included studies. Study authors were contacted for further information. Meta-analyses were performed using risk ratios (RR) and risk differences (RD) for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals (CI). We included 11 randomised controlled trials in this updated review, comprising 1505 term and late preterm infants with moderate/severe encephalopathy and evidence of intrapartum asphyxia
Frijlink, Daphne W; Tilanus, Joachim J; Roks, Gerwin
Wernicke encephalopathy (WE) commonly presents with oculomotor abnormalities, gait ataxia and confusion. WE can mimic rapidly progressive dementia syndromes, such as Creutzfeldt-Jakob disease (CJD). Cerebrospinal fluid (CSF) tau is frequently used for diagnosis of several dementia subtypes, predominantly CJD and Alzheimer's disease. The combination of very high CSF tau (tau) and normal phosphorylated tau (p-tau) levels is almost exclusively seen in aggressive diseases, such as CJD. The authors present a case of a woman with WE, caused by chronic insufficient dietary intake, with highly elevated CSF tau and normal p-tau. The clinical symptoms and CSF findings raised the suspicion of CJD. However, shortly after immediate treatment with thiamine the patient clinically improved. At follow-up, 2.5 months later, she had made a good recovery. This case of rapidly progressive dementia illustrates that, even in the case of a highly elevated CSF tau, clinicians should be alert for treatable causes such as WE.
Peleman, Cedric; Camilleri, Michael
Rifaximin is beneficial in the treatment of minimal hepatic encephalopathy (MHE). Kang et al. (Clin Transl Gastroenterol 7: e187; doi:10.1038/ctg.2016.44) investigated the effects of rifaximin in a mouse model of MHE-associated microbiota without concomitant liver disease. In addition to some impact on the composition of microbiota, rifaximin altered bacterial functions, ameliorated local and systemic inflammation, and reduced enterocyte glutaminase activity. We discuss these effects as well as the interpretation of the permeability studies, given the potential interaction of dysbiosis with dysfunctional intestinal barrier, leading to systemic inflammation and increased uptake of bacterial metabolites that contribute to MHE in the presence of hepatic dysfunction. PMID:27711069
Atluri, Dileep K; Prakash, Ravi; Mullen, Kevin D
Hepatic encephalopathy (HE) is a neuropsychiatric disorder seen in patients with advanced liver disease or porto-systemic shunts. Based on etiology and severity of HE, the World Congress of Gastroenterology has divided HE into categories and sub-categories. Many user-friendly computer-based neuropsychiatric tests are being validated for diagnosing covert HE. Currently, emphasis is being given to view HE deficits as a continuous spectrum rather than distinct stages. Ammonia is believed to play crucial role in pathogenesis of HE via astrocyte swelling and cerebral edema. However, evidence has been building up which supports the synergistic role of oxidative stress, inflammation and neurosteroids in pathogenesis of HE. At present, treatment of HE aims at decreasing the production and intestinal absorption of ammonia. But as the role of new pathogenetic mechanisms becomes clear, many potential new treatment strategies may become available for clinician. PMID:25755319
Ramos, Cristina Giesta; Pereira, Cláudia
Wernicke Encephalopathy (WE) is a severe neurological disease caused by vitamin B1 (thiamine) deficiency, which is potentially treatable if early diagnosed. This is the clinical case of a young female patient, with renal insufficiency on haemodialysis, who has been submitted to an abdominal surgery. After the intervention, there were difficulties on beginning with enteric nutrition. Some days later she developed gait imbalance. A Brain Magnetic Resonance (MR) was performed and disclosed abnormalities suggestive of WE. After treatment with thiamine, the patient became asymptomatic. Brain MR is crucial for the confirmation of the diagnosis and early detection of WE, as the imagiologic pattern is typical and the clinical diagnosis is frequently difficult to obtain.
Dixon, Brandon J.; Reis, Cesar; Ho, Wing Mann; Tang, Jiping; Zhang, John H.
Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. PMID:26389893
Singer, H.; Harrison, A. W.; Aggett, P. W.
A 64-year-old alcoholic patient with cirrhosis and bleeding esophageal varices developed hepatic encephalopathy following portacaval shunt. The etiology of this syndrome is believed to be related to the absorption of toxic nitrogenous substances derived from the activity of bacteria in the large bowel. Treatment consisted of a low protein diet, frequent purgation, and oral neomycin. Even on a 20-g. protein diet the patient deteriorated to a state approaching coma. Colectomy with ileorectal anastomosis was performed with good result. The patient remained alert and active with no recurrences of cerebral disturbance while enjoying a 60-g. protein diet. No additional treatment was necessary. The literature on colectomy in the treatment of this condition, while brief, reports similar good results. Further trial of colectomy is recommended for cases refractory to more conservative methods of management. PMID:5831216
Limketkai, Berkeley N; Zucker, Stephen D
Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level was elevated at 276 microg/dL. Traditional ammonia-reducing therapies were initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune causes for the hyperammonemia were excluded. The patient was severely malnourished and her carnitine level was found to be extremely low. After carnitine supplementation, ammonia levels normalized and the patient's mental status returned to baseline. In the setting of refractory hyperammonemia, this case illustrates how careful investigation may reveal a treatable condition.
Cantu, Robert; Chin, Lawrence S.
Chronic traumatic encephalopathy (CTE) is a devastating neuropsychological condition afflicting a small percentage of athletes partaking in high-impact sports. The onset of symptoms lags years behind the inciting events. Repetitive minor head injuries are felt to be the main etiology behind CTE. Routine radiographic imaging generally is unremarkable in cases of CTE. Functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are advanced MRI-based sequences that have shown promise in detecting early radiographic findings that may be reflective of CTE. Progressive neuronal loss is the histopathological hallmark of this neurodegenerative disease. Strategizing earlier detection techniques is paramount in delivering optimal care to athletes afflicted with CTE. PMID:27088064
Harrison, Rebecca A; Vu, Trung; Hunter, Alan J
Clinically, we most often associate Wernicke's encephalopathy (WE) with an alcohol abusing population. However, it is important to consider other causes of malnutrition and vitamin deficiency as risk factors for the development of this disorder. We present a case of a 51-year-old man with schizophrenia and malnutrition who presented with delirium, ophthalmoplegia, and seizures. He responded rapidly to the administration of IV thiamine. Because of the high rate of mortality and morbidity, WE should be high on the differential of any patient at risk for malnutrition or with ophthalmoplegia, regardless of alcohol history. This is particularly important in psychiatric patients where the syndrome may be masked and thus treatment delayed. PMID:16925799
Wicklund, Meredith R; Knopman, David S
A 71-year-old woman with myelofibrosis on chemotherapy experienced an acute illness with nausea, vomiting, and diarrhea. Two weeks later, she developed an acute confusional state characterized by disorientation and fluctuating alertness with normal speech and language. Her neurologic examination demonstrated an upper motor neuron pattern of right hemiparesis. She reported double vision though ophthalmoparesis was not appreciated. Her gait was normal. While hospitalized, she developed generalized tonic-clonic seizures. Brain MRI revealed a small area of restricted diffusion of the left precentral gyrus (figure). She was diagnosed with a stroke with secondary seizures; however, as the confusional state resolved, she developed profound retrograde and anterograde amnesia. Review of the brain MRI showed high T2 signal in the medial thalamus and contrast enhancement of the mamillary bodies; a diagnosis of Wernicke-Korsakoff syndrome was entertained and she was started on thiamine replacement. The encephalopathy and hemiparesis resolved though she remains severely amnestic.
Lough, Mary E
Wernicke's encephalopathy (WE) is a life threatening neurological disorder that results from thiamine (Vitamin B1) deficiency. Clinical signs include mental status changes, ataxia, occulomotor changes and nutritional deficiency. The conundrum is that the clinical presentation is highly variable. WE clinical signs, brain imaging, and thiamine blood levels, are reviewed in 53 published case reports from 2001 to 2011; 81 % (43/53) were non-alcohol related. Korsakoff Syndrome or long-term cognitive neurological changes occurred in 28 % (15/53). Seven WE cases (13 %) had a normal magnetic resonance image (MRI). Four WE cases (8 %) had normal or high thiamine blood levels. Neither diagnostic tool can be relied upon exclusively to confirm a diagnosis of WE.
Miller, D L; Ross, E M
Data from the first year of the National Childhood Encephalopathy Study were reviewed to see whether any relation was apparent between pertussis vaccination and brain disease. Three hundred and eighty-seven cases of encephalitis and other specified neurological conditions in which the children were admitted to hospital were reported, of which 267 satisfied the study criteria. Control children were matched for age with the index cases, and medical and immunisation histories were reviewed. Few of the index cases had been vaccinated within 28 days before admission to hospital, so that no close association between vaccination and brain disease existed in most cases. The number of children who had recently been immunised was too small for any statistically useful conclusion to be reached about the risk associated with pertussis vaccine. The study is continuing. PMID:709204
Bertrand, A; Brandel, J P; Grignon, Y; Sazdovitch, V; Seilhean, D; Faucheux, B; Privat, N; Brault, J L; Vital, A; Uro-Coste, E; Pluot, M; Chapon, F; Maurage, C A; Letournel, F; Vespignani, H; Place, G; Degos, C F; Peoc'h, K; Haïk, S; Hauw, J J
We assessed the prevalence of Wernicke encephalopathy (WE) in all 657 cases suspected of Creutzfeldt-Jakob (CJD) referred from 2001 to 2006 to the French Neuropathology Network of CJD. Clinical, biological and imaging data were reviewed when the diagnosis of WE was made at autopsy. No CJD was found in five cases suspected of sporadic CJD. In these five cases, myoclonus had been observed in four, CSF 14-3-3 protein in two. In 14 other cases, WE was combined with CJD, 13 of which were sporadic. These belonged mainly to the molecular variants of sporadic CJD associated with a long duration of disease. This stresses the necessity of remaining alert to the diagnosis of WE when CJD is suspected.
Carrabba, G; Fava, E; Giussani, C; Acerbi, F; Portaluri, F; Songa, V; Stocchetti, N; Branca, V; Gaini, S M; Bello, L
Surgery for gliomas located inside or in proximity of motor cortex or tracts requires cortical and subcortical mapping to locate motor function; direct electrical stimulation of brain cortex or subcortical pathways allows identification and preservation of motor function. In this study we evaluated the effect which subcortical motor mapping had on postoperative morbidity and extent of resection in a series of patients with gliomas involving motor areas or pathways. One hundred and forty-six patients were included in the study. Intraoperative findings of primary motor cortex or subcortical tracts were reported, together with incidence of new postoperative deficits at short (1 week) and long term (1 month) examination. The relationship between intraoperative identification of subcortical motor tracts and extent of resection was reported. The motor strip was found in 133 patients (91%) and subcortical motor tracts in 91 patients (62.3%). New immediate postoperative motor deficits were documented in 59.3% of patients in whom a subcortical motor tract was identified intra-operatively and in 10.9% of those in whom subcortical tracts were not observed; permanent deficits were observed in 6.5% and 3.5%, respectively. A total resection was achieved in 94.4% of patients with high-grade gliomas and in 46.1% of those with low-grade gliomas.
Pietranera, Luciana; Brocca, Maria Elvira; Roig, Paulina; Lima, Analia; Garcia-Segura, Luis Miguel; De Nicola, Alejandro F
Estrogens are neuroprotective factors for brain diseases, including hypertensive encephalopathy. In particular, the hippocampus is highly damaged by high blood pressure, with several hippocampus functions being altered in humans and animal models of hypertension. Working with a genetic model of primary hypertension, the spontaneously hypertensive rat (SHR), we have shown that SHR present decreased dentate gyrus neurogenesis, astrogliosis, low expression of brain derived neurotrophic factor (BDNF), decreased number of neurons in the hilus of the dentate gyrus, increased basal levels of the estrogen-synthesizing enzyme aromatase, and atrophic dendritic arbor with low spine density in the CA1 region compared to normotensive Wistar Kyoto (WKY) ratsl. Changes also occur in the hypothalamus of SHR, with increased expression of the hypertensinogenic peptide arginine vasopressin (AVP) and its V1b receptor. Following chronic estradiol treatment, SHR show decreased blood pressure, enhanced hippocampus neurogenesis, decreased the reactive astrogliosis, increased BDNF mRNA and protein expression in the dentate gyrus, increased neuronal number in the hilus of the dentate gyrus, further increased the hyperexpression of aromatase and replaced spine number with remodeling of the dendritic arbor of the CA1 region. We have detected by qPCR the estradiol receptors ERα and ERβ in hippocampus from both SHR and WKY rats, suggesting direct effects of estradiol on brain cells. We hypothesize that a combination of exogenously given estrogens plus those locally synthesized by estradiol-stimulated aromatase may better alleviate the hippocampal and hypothalamic encephalopathy of SHR. This article is part of a Special Issue entitled "Sex steroids and brain disorders". Copyright © 2014 Elsevier Ltd. All rights reserved.
Kircheis, Gerald; Knoche, Anja; Hilger, Norbert; Manhart, Frank; Schnitzler, Alfons; Schulze, Horst; Häussinger, Dieter
Low-grade hepatic encephalopathy (HE) may impair fitness to drive. Driving deficits have not yet been characterized, and their relation to psychometric test results is unclear. Fifty-one cirrhotic patients and 48 age-matched controls underwent real driving in a multiple sensor and camera-equipped car, laboratory and "in-car" computer psychometry, and driving instructor's assessment. Ten cirrhotic patients had no hepatic encephalopathy (HE0); 27 and 14 patients suffered from minimal HE (mHE) and overt HE grade I (oHE), respectively. During real driving, mHE and oHE patients showed significantly more violations of in-lane keeping, reduced break use, prolonged reaction times, and diminished stress tolerance compared with control or cirrhotic HE0 patients. In a self-evaluation questionnaire, mHE and oHE, but not the HE0, patients strongly overestimated their driving abilities. According to the driving instructor's assessment, 75%, 48%, and 39% of the patients with HE0, mHE, and oHE, respectively, were fit to drive, compared with 87% in the control group. Driving deficits in oHE patients were largely due to cognitive defects and prolonged reaction times, whereas, in mHE patients, mistakes and attention deficits predominated. Computer psychometric test results worsened with HE severity and age, whereas real driving was age independent. In 25 out of 94 patients, discordant results for driving fitness were obtained (driving instructor's assessment vs computer psychometry); in mHE and oHE patients, the concordance rates were only 62% and 64%, respectively. Despite significant driving deficits, HE patients overestimate their driving abilities. The presence of mHE does not necessarily predict driving unfitness, and computer-based testings cannot reliably predict driving fitness.
Tsutsui, Toshiyuki; Kasuga, Fumiko
Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.
Armstrong, Richard A; McKee, Ann C; Cairns, Nigel J
To investigate neuropathological changes in the superior colliculus in chronic traumatic encephalopathy. The densities of the tau-immunoreactive neurofibrillary tangles, neuropil threads, dot-like grains, astrocytic tangles, and neuritic plaques, together with abnormally enlarged neurons, typical neurons, vacuolation, and frequency of contacts with blood vessels, were studied across the superior colliculus from pia mater to the periaqueductal gray in eight chronic traumatic encephalopathy and six control cases. Tau-immunoreactive pathology was absent in the superior colliculus of controls but present in varying degrees in all chronic traumatic encephalopathy cases, significant densities of tau-immunoreactive neurofibrillary tangles, NT, or dot-like grains being present in three cases. No significant differences in overall density of the tau-immunoreactive neurofibrillary tangles, neuropil threads, dot-like grains, enlarged neurons, vacuoles, or contacts with blood vessels were observed in control and chronic traumatic encephalopathy cases, but chronic traumatic encephalopathy cases had significantly lower mean densities of neurons. The distribution of surviving neurons across the superior colliculus suggested greater neuronal loss in intermediate and lower laminae in chronic traumatic encephalopathy. Changes in density of the tau-immunoreactive pathology across the laminae were variable, but in six chronic traumatic encephalopathy cases, densities of tau-immunoreactive neurofibrillary tangles, neuropil threads, or dot-like grains were significantly greater in intermediate and lower laminae. Pathological changes were not correlated with the distribution of blood vessels. The data suggest significant pathology affecting the superior colliculus in a proportion of chronic traumatic encephalopathy cases with a laminar distribution which could compromise motor function rather than sensory analysis.
HASSANZADEH RAD, Afagh; AMINZADEH, Vahid
Acute Necrotizing Encephalopathy of childhood (ANEC) is a specific type of encephalopathy. After viral infection, it can be diagnosed by bilateral symmetrical lesions predominantly observed in thalami & brainstem of infants & children. Although, it is commonly occurred in Japanese and Taiwanese population. The goal of this article is to report a rare case of ANEC in a 15 months old girl infant from Thaleghani Hospital, Ramian, Gorgan, northern Iran. PMID:28277560
Maramattom, Boby Varkey; Raja, Rajat; Balagopal, Anuroop
Urea cycle disorders (UCD) are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD) is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual. We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain. PMID:27570396
Kankirawatana, P; Leonard, H; Ellaway, C; Scurlock, J; Mansour, A; Makris, C M; Dure, L S; Friez, M; Lane, J; Kiraly-Borri, C; Fabian, V; Davis, M; Jackson, J; Christodoulou, J; Kaufmann, W E; Ravine, D; Percy, A K
MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.
Jain, Puneet; Tripathi, Manjari
Epileptic encephalopathies refer to a group of disorders in which the unremitting epileptic activity contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone, and these can worsen over time leading to progressive cerebral dysfunction. Several syndromes have been described based on their electroclinical features (age of onset, seizure type, and EEG pattern). This review briefly describes the clinical evaluation and management of commonly encountered epileptic encephalopathies in children. PMID:23970964
Torkamani, Ali; Bersell, Kevin; Jorge, Benjamin S; Bjork, Robert L; Friedman, Jennifer R; Bloss, Cinnamon S; Cohen, Julie; Gupta, Siddharth; Naidu, Sakkubai; Vanoye, Carlos G; George, Alfred L; Kearney, Jennifer A
Numerous studies have demonstrated increased load of de novo copy number variants or single nucleotide variants in individuals with neurodevelopmental disorders, including epileptic encephalopathies, intellectual disability, and autism. We searched for de novo mutations in a family quartet with a sporadic case of epileptic encephalopathy with no known etiology to determine the underlying cause using high-coverage whole exome sequencing (WES) and lower-coverage whole genome sequencing. Mutations in additional patients were identified by WES. The effect of mutations on protein function was assessed in a heterologous expression system. We identified a de novo missense mutation in KCNB1 that encodes the KV 2.1 voltage-gated potassium channel. Functional studies demonstrated a deleterious effect of the mutation on KV 2.1 function leading to a loss of ion selectivity and gain of a depolarizing inward cation conductance. Subsequently, we identified 2 additional patients with epileptic encephalopathy and de novo KCNB1 missense mutations that cause a similar pattern of KV 2.1 dysfunction. Our genetic and functional evidence demonstrate that KCNB1 mutation can result in early onset epileptic encephalopathy. This expands the locus heterogeneity associated with epileptic encephalopathies and suggests that clinical WES may be useful for diagnosis of epileptic encephalopathies of unknown etiology. © 2014 American Neurological Association.
Bjork, Robert L.; Friedman, Jennifer R.; Bloss, Cinnamon S.; Cohen, Julie; Gupta, Siddharth; Naidu, Sakkubai; Vanoye, Carlos G.; George, Alfred L.; Kearney, Jennifer A.
Background Numerous studies have demonstrated increased load of de novo copy number variants (CNVs) or single nucleotide variants (SNVs) in individuals with neurodevelopmental disorders, including epileptic encephalopathies, intellectual disability and autism. Methods We searched for de novo mutations in a family quartet with a sporadic case of epileptic encephalopathy with no known etiology to determine the underlying cause using high coverage whole exome sequencing (WES) and lower coverage whole genome sequencing (WGS). Mutations in additional patients were identified by WES. The effect of mutations on protein function was assessed in a heterologous expression system. Results We identified a de novo missense mutation in KCNB1 that encodes the KV2.1 voltage-gated potassium channel. Functional studies demonstrated a deleterious effect of the mutation on KV2.1 function leading to a loss of ion selectivity and gain of a depolarizing inward cation conductance. Subsequently, we identified two additional patients with epileptic encephalopathy and de novo KCNB1 missense mutations that cause a similar pattern of KV2.1 dysfunction. Interpretation Our genetic and functional evidence demonstrate that KCNB1 mutation can result in early onset epileptic encephalopathy. This expands the locus heterogeneity associated with epileptic encephalopathies and suggests that clinical WES may be useful for diagnosis of epileptic encephalopathies of unknown etiology. PMID:25164438
Feyissa, Anteneh M; Tummala, Sudhakar
Ifosfamide is an alkylating agent useful in the treatment of a wide range of cancers including sarcomas, lymphoma, gynecologic and testicular cancers. Encephalopathy has been reported in 10-40% of patients receiving high-dose IV ifosfamide. To highlight the role of electroencephalogram (EEG) in the early detection and management of ifosfamide related encephalopathy. Retrospective chart review including clinical data and EEG recordings was done on five patients, admitted to MD Anderson Cancer Center between years 2009 and 2012, who developed ifosfamide related acute encephalopathy. All five patients experienced symptoms of encephalopathy soon after (within 12 h-2 days) receiving ifosfamide. Two patients developed generalized convulsions while one patient developed continuous non-convulsive status epilepticus (NCSE) that required ICU admission and intubation. Initial EEG showed epileptiform discharges in three patients; run of triphasic waves in one patient and moderate degree diffuse generalized slowing. Mixed pattern with the presence of both sharps and triphasic waves were also noted. Repeat EEGs within 24_h of symptom onset showed marked improvement that was correlated with clinical improvement. Severity of ifosfamide related encephalopathy correlates with EEG changes. We suggest a timely EEG evaluation for patients receiving ifosfamide who develop features of encephalopathy. © 2013.
Kircheis, Gerald; Fleig, Wolfgang E; Görtelmeyer, Roman; Grafe, Susanne; Häussinger, Dieter
The value of paper-pencil tests and West-Haven-criteria for assessment of low-grade hepatic encephalopathy under conditions of a randomized, double-blind, placebo-controlled, clinical trial was evaluated in a cohort of 217 cirrhotics. Patients were graded at least twice clinically for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery. Re-evaluation of the study documentation showed that at study entry 33% and during the study even 50% of the patients were wrongly allocated to minimal or overt hepatic encephalopathy. Despite the participating physicians' training, 31% of the number-connection-tests-A, 20% of the number-connection-tests-B and 28% of the line-tracing-test were in retrospect considered invalid by an independent psychologist. Neither the Portosystemic-Encephalopathy-Syndrome (PSE) test nor the Psychometric-Hepatic-Encephalopathy-Sum (PHES)-score reliably picked up clinical improvement in the individual patient. Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy, the clinical classification of individual patients into one of the groups will have a high rate of error. The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test. Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven-criteria and paper-pencil tests including related scores for quantification of low-grade HE at least in multicenter approaches.
Tentolouris-Piperas, Vasileios; Ryan, Natalie S; Thomas, David L; Kinnunen, Kirsi M
Recent brain imaging studies have found changes in subcortical regions in presymptomatic autosomal dominant Alzheimer's disease (ADAD). These regions are also affected in sporadic Alzheimer's disease (sAD), but whether such changes are seen in early-stage disease is still uncertain. In this review, we discuss imaging studies published in the past 12 years that have found evidence of subcortical involvement in early-stage ADAD and/or sAD. Several papers have reported amyloid deposition in the striatum of presymptomatic ADAD mutation carriers, prior to amyloid deposition elsewhere. Altered caudate volume has also been implicated in early-stage ADAD, but findings have been variable. Less is known about subcortical involvement in sAD: the thalamus and striatum have been found to be atrophied in symptomatic patients, but their involvement in the preclinical phase remains unclear, in part due to the difficulties of studying this stage in sporadic disease. Longitudinal imaging studies comparing ADAD mutation carriers with individuals at high-risk for sAD may be needed to elucidate the significance of subcortical involvement in different AD clinical stages. Copyright © 2016 Elsevier B.V. All rights reserved.
Bouvier, Liziane; Groulx, Bertrand; Martel-Sauvageau, Vincent; Monetta, Laura
Language disorders following subcortical non-thalamic stroke show great variability across literature and a well-defined profile in these aphasic disturbances is yet to be established. The lack of recent and consistent literature on the subject complicates the management of subcortical aphasia. The aim of this study is to review the literature describing oral language disturbances following subcortical non-thalamic stoke affecting the basal ganglia and the surrounding white matter. A review of the literature of three databases (PubMed, PsycNet and LLBA), identifying research articles from 1997 to 2015, was completed. The quality of the selected studies was assessed using the Checklist for the assessment of methodological quality. Twenty-two articles met criteria for review and oral language assessment data were extracted for 114 subjects. The results suggest a predominance of deficits in more complex and demanding language levels (ex. discourse, syntax) and in language production (vs comprehension). Rapid recovery is expected, especially for lexical-semantic and receptive deficits. These findings show the importance of a complete oral language evaluation after subcortical stoke and provide recent data relative to expected deficits and recovery to guide clinicians in the management of these patients. They also suggest that a descriptive approach of the deficits may be more efficient and accurate than the use of a traditional classification of aphasia.
Jensen, Angela M.; Chenery, Helen J.; Copland, David A.
The lexical-semantic and syntactic abilities of a group of individuals with chronic nonthalamic subcortical (NS) lesions following stroke (n=6) were investigated using the Western Aphasia Battery (WAB) picture description task [Kertesz, A. (1982). "The Western aphasia battery." New York: Grune and Stratton] and compared with those of a…
Zhang, Quan; Zhang, Yunting; Zhang, Jing; Li, Qiong
We report 2 cases of subcortical band heterotopia (SBH) with emphasis on double inversion recovery (DIR) magnetic resonance imaging (MRI). The heterotopic gray matter demonstrated homogeneous high signal intensity and the delineation between the SBH and white matter was distinctly depicted on DIR MRI. Double inversion recovery is a useful adjunct to conventional MRI for the diagnosis of SBH.
This paper considers the process by which humans are able to select from the complex string of sounds impinging on the ear and understand certain frequency combinations to be linguistic signals while other combinations are not. A brief review of the complex subcortical region, particularly the known but seldom studied reticular system, indicates…
Mozaz, M; Marti, J F; Carrera, E; De la Puente, E
This report describes a case of apraxia caused by a right sided sub-cortical lesion. Performance on test for apraxia was impaired. A new type of error which involved demonstrating the use of objects on one's own body is reported. Some theoretical interpretations of the findings are discussed.
Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy; Sidtis, John J.
Purpose: The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of…
Gartner, B; Seeck, M; Michel, C; Delavelle, J; Lazeyras, F
Background: Evidence from previous volumetric magnetic resonance studies has revealed that patients with chronic temporal lobe epilepsy show atrophy of distinct subcortical nuclei, predominantly ipsilateral to the focus side. We were interested to find out if there is also selective subcortical atrophy in patients suffering from long standing extratemporal lobe epilepsy. Methods: Thirty one patients in whom pre-surgical evaluation unambiguously localised an extratemporal focus were included in this study. Using high resolution magnetic resonance imaging, the volumes of the caudate nuclei, putamen, pallidum, and thalamus were measured bilaterally in both hemispheres and compared with measurements obtained in 15 healthy volunteers. Results: No significant difference in volumes was found between the two subject groups, or in any subgroup of extratemporal lobe epilepsy patients, nor was there any relation to clinical variables such as age of onset, overall seizure frequency, or disease duration. However, patients who had no or only rare generalised tonic–clonic seizures seemed to differ from the other patients and controls in that they had smaller putamen volumes bilaterally (p<0.001). Conclusion: We concluded that extratemporal lobe epilepsy in general is not associated with diminished volumes in the studied subcortical structures, which contrasts with findings in temporal lobe epilepsy patients. Thus, both entities differ both cortically and subcortically. However, we found that small putamen volume was bilaterally associated with absent or rare generalised tonic–clonic seizures, implicating the putamen in the control of the most disabling seizure type, independent of the site of neocortical focus. PMID:15026503
Liu, P; Yang, J; Wang, G; Liu, Y; Liu, X; Jin, L; Liang, F; Qin, W; Calhoun, V D
There is emerging evidence that primary dysmenorrhoea (PDM) is associated with altered brain function and structure. However, few studies have investigated changes in regional cortical thickness and subcortical volumes in PDM patients. The purpose of this study was to characterize differences in both cortical thickness and subcortical volumes between PDM patients and healthy controls (HCs). T1-weighted magnetic resonance images were obtained from 44 PDM patients and 32 HCs matched for age and handedness. Cortical thickness was compared in multiple locations across the continuous cortical surface, and subcortical volumes were compared on a structure-by-structure basis. Correlation analysis was then used to evaluate relationships between the clinical symptoms and abnormal brain structure in PDM. PDM patients had significantly increased cortical thickness in the orbitofrontal cortex (OFC), insula (IN), primary/secondary sensory area (SI/SII), superior temporal cortex (STC), precuneus (pCUN) and posterior cingulate cortex (PCC). Meanwhile, significantly decreased subcortical volumes of the caudate, thalamus and amygdala were found in PDM patients. Moreover, there were significant positive correlations between the PDM-related duration and the OFC, SFC, STC and IN. The MPQ scores were positively correlated with the pCUN. These findings provide further evidence for grey matter changes in patients with PDM, and in addition, the results support relationships between the structural abnormalities and their role in symptom production. All these results are likely to be potential valuable to provide us with direct information about the neural basis of PDM. © 2015 European Pain Federation - EFIC®
Jensen, Angela M.; Chenery, Helen J.; Copland, David A.
The lexical-semantic and syntactic abilities of a group of individuals with chronic nonthalamic subcortical (NS) lesions following stroke (n=6) were investigated using the Western Aphasia Battery (WAB) picture description task [Kertesz, A. (1982). "The Western aphasia battery." New York: Grune and Stratton] and compared with those of a…
Van Lancker Sidtis, Diana; Choi, JiHee; Alken, Amy; Sidtis, John J.
Purpose: The production of formulaic expressions (conversational speech formulas, pause fillers, idioms, and other fixed expressions) is excessive in the left hemisphere and deficient in the right hemisphere and in subcortical stroke. Speakers with Alzheimer's disease (AD), having functional basal ganglia, reveal abnormally high proportions of…
Nighoghossian, N; Berthezene, Y; Adeleine, P; Wiart, M; Damien, J; Derex, L; Itti, R; Froment, J C; Trouillas, P
A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.
Muthuraman, M; Hellriegel, H; Groppa, S; Deuschl, G; Raethjen, J
The aim of this study was to find the cortical and sub-cortical network responsible for the sensory evoked coherence in healthy subjects during electrical stimulation of right median nerve at wrist. The multitaper method was used to estimate the power and coherence spectrum followed by the source analysis method dynamic imaging of coherent sources (DICS) to find the highest coherent source for the basic frequency 3 Hz and the complete cortical and sub-cortical network responsible for the sensory evoked coherence in healthy subjects. The highest coherent source for the basic frequency was in the posterior parietal cortex for all the subjects. The cortical and sub-cortical network comprised of the primary sensory motor cortex (SI), secondary sensory motor cortex (SII), frontal cortex and medial pulvinar nucleus in the thalamus. The cortical and sub-cortical network responsible for the sensory evoked coherence was found successfully with a 64-channel EEG system. The sensory evoked coherence is involved with a thalamo-cortical network in healthy subjects.
Coplan, Jeremy D.; Hodulik, Sarah; Mathew, Sanjay J.; Mao, Xiangling; Hof, Patrick R.; Gorman, Jack M.; Shungu, Dikoma C.
We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging (1H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ’s and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans. PMID:22347183
Lorio, S.; Fresard, S.; Adaszewski, S.; Kherif, F.; Chowdhury, R.; Frackowiak, R.S.; Ashburner, J.; Helms, G.; Weiskopf, N.; Lutti, A.; Draganski, B.
Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains. PMID:26854557
Jouvent, Eric; Sun, Zhong Yi; De Guio, François; Duchesnay, Edouard; Duering, Marco; Ropele, Stefan; Dichgans, Martin; Mangin, Jean-François; Chabriat, Hugues
Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases. Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is independently associated with disability in patients with a positive history of small subcortical ischemic stroke. Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and sulcal shape. Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education (proportional odds ratio =1.19, 95% confidence interval =1.06-1.35; P=0.002). Results remained significant after further adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular origin. The severity of disability in patients with a positive history of small subcortical ischemic stroke caused by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity in patients with a positive history of small subcortical ischemic stroke. © 2016 American Heart Association, Inc.
Bunyaratavej, Krishnapundha; Sangtongjaraskul, Sunisa; Lerdsirisopon, Surunchana; Tuchinda, Lawan
To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions. Copyright © 2016 Elsevier B.V. All rights reserved.
Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun
Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.
Edmonds, Emily C.; Bangen, Katherine J.; Delano-Wood, Lisa; Nation, Daniel A.; Furst, Ansgar J.; Salmon, David P.; Bondi, Mark W.
Objectives We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. PMID:27903335
Schanen, N.C.; Glusker, P.; Chung, M.
Binswanger encephalopathy is a clinicopathologic entity characterized by deep white matter ischaemic lesions associated with hypertension and arteriosclerosis; but a rare inherited form, termed CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) has been recently described with earlier onset in the absence of hypertension. This syndrome has been linked to markers in chromosome band 19q12 in of two unrelated French families. We have identified a family of Central American heritage with a similar syndrome also demonstrating an autosomal dominant pattern of inheritance. Clinically, the onset of symptoms is between 19-53 years of age with variable progression in loss of neurologic function. Numerous lesions are visible on MRI involving the deep white matter including the corpus callosum as well as basal ganglia. None of the family members has had significant hypertension. Extensive evaluations of metabolic, infectious and inflammatory origin of disease have been noncontributory. In the two patients whose brains were examined pathologically, multiple cystic lesions, frequently centered around blood vessels, were present in the deep white matter and basal ganglia with diffuse loss of myelin and relative preservation of the neurons. The media of large and small parenchymal arteries shows hyaline and hydropic degeneration with replacement of the smooth muscle by a slate-grey amorphous substance on trichrome staining, corresponding to granular osmiophilic material on ultrastructural examination. There was no evidence of amyloid or atherosclerosis in the vessels. Phenotypically, this family appears to have the CADASIL syndrome. We are currently pursuing linkage analysis with chromosome 19 markers to investigate the genetic homogeneity of the disorder. Thirty-three individuals spanning three generations and including seven clinically affected patients are potentially available for study.
Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A
Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory Committee... be open to the public. Name of Committee: Transmissible Spongiform Encephalopathies Advisory...
Lockwood, A H; Ginsberg, M D; Rhoades, H M; Gutierrez, M T
The regional cerebral metabolic rate for glucose was measured in normal and portacaval shunted rats and the effects of unilateral carotid infusions of "threshold" amounts of ammonia were assessed. 8 wk after shunting the glucose metabolic rate was increased in all 20 brain regions sampled. Effects on subcortical and phylogenetically older regions of the brain were most pronounced with a 74% increase observed in the reticular formation at the collicular level. Increases in the cerebral cortex ranged from 12 to 18%. Unilateral infusions of ammonia did not affect behavior but altered the electroencephalogram and selectively increased the glucose metabolic rate in the thalamus, hypothalamus, and substantia nigra in half of the animals, a pattern similar to that seen after a portacaval shunt, suggesting hyperammonemia as the cause of postshunt increases in glucose metabolism. Visual inspection of autoradiograms, computed correlation coefficients relating interregional metabolism, and principal component analysis suggest that normal cerebral metabolic and functional interrelationships are altered by shunting. Ammonia stimulation of the hypothalamic satiety centers may suppress appetite and lead to cachexia. Reductions in the ammonia detoxification capacity of skeletal muscle may increase the probability of developing future episodes of hyperammonemia, perpetuating the process. Direct effects of ammonia on specific brain centers such as the dorsomedial hypothalamus and reticular activating system may combine with global disruptions of cerebral metabolic-functional relationships to produce the protean manifestations of portal-systemic encephalopathy. Images PMID:3722388
Traul, David E; Traul, Christine S; Matsumoto, Julie; Goodkin, Howard P
We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity.
Lindå, Hans; von Heijne, Anders
We describe posterior reversible encephalopathy syndrome (PRES) in a woman with multiple sclerosis treated with Gilenya(®) (Fingolimod). The first symptoms appeared after 21 months of fingolimod treatment. She experienced headache, altered mental status, cognitive deficits, seizures, and visual disturbances. Not at any time during the course of the disease could any signs of infection or rheumatic disorder be detected. Test for anti-neuronal antibodies was also negative. Her blood pressure was normal. MRI showed widespread cortical and subcortical changes with some mass-effect in the temporo-occipital-parietal lobes in the left hemisphere. Contrast enhancement was seen in the leptomeninges and, in addition, there were no areas with restricted diffusion and no signs of hemorrhage. Her condition deteriorated until fingolimod was discontinued. Slowly her condition improved and after 8 months, the only symptoms that remained were two small, non-corresponding, right inferior scotomas. We believe that all symptoms, the clinical course, and the MRI findings in this case can all be explained by considering PRES, a probably rare, but serious, side effect of fingolimod treatment.
Lucke-Wold, Brandon Peter; Turner, Ryan Coddington; Logsdon, Aric Flint; Bailes, Julian Edwin; Huber, Jason Delwyn; Rosen, Charles Lee
Significant attention has recently been drawn to the potential link between head trauma and the development of neurodegenerative disease, namely chronic traumatic encephalopathy (CTE). The acute neurotrauma associated with sports-related concussions in athletes and blast-induced traumatic brain injury in soldiers elevates the risk for future development of chronic neurodegenerative diseases such as CTE. CTE is a progressive disease distinguished by characteristic tau neurofibrillary tangles (NFTs) and, occasionally, transactive response DNA binding protein 43 (TDP43) oligomers, both of which have a predilection for perivascular and subcortical areas near reactive astrocytes and microglia. The disease is currently only diagnosed postmortem by neuropathological identification of NFTs. A recent workshop sponsored by National Institute of Neurological Disorders and Stroke emphasized the need for premortem diagnosis, to better understand disease pathophysiology and to develop targeted treatments. In order to accomplish this objective, it is necessary to discover the mechanistic link between acute neurotrauma and the development of chronic neurodegenerative and neuropsychiatric disorders such as CTE. In this review, we briefly summarize what is currently known about CTE development and pathophysiology, and subsequently discuss injury-induced pathways that warrant further investigation. Understanding the mechanistic link between acute brain injury and chronic neurodegeneration will facilitate the development of appropriate diagnostic and therapeutic options for CTE and other related disorders.
Akazawa, Yohei; Inaba, Yuji; Hachiya, Akira; Motoki, Noriko; Matsuzaki, Satoshi; Minatoya, Kenji; Morisaki, Takayuki; Morisaki, Hiroko; Kosaki, Kenjiro; Kosho, Tomoki; Koike, Kenichi
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder, caused by heterozygous mutations in TGFBR1 or TGFBR2 and characterized by vascular complications (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections) and skeletal manifestations. We here report the first patient with LDS presenting with reversible cerebral vasoconstriction syndrome (RCVS), a clinico-radiological condition characterized by recurrent thunderclap headaches, with or without neurological symptoms, and reversible vasoconstriction of cerebral arteries. The patient was a 9-year-old boy with a heterozygous TGFBR2 mutation, manifesting camptodactyly, talipes equinovarus, and lamboid craniosynostosis. He complained of severe recurrent headaches 2 months after total aortic replacement for aortic root dilatation and a massive Stanford type B aortic dissection. A thoracic CT scan revealed a left subclavian artery dissection. Brain MRI and MRA detected bilateral internal carotid artery constriction along with a cortical subarachnoid hemorrhage without intracranial aneurysms. Subsequently, he developed visual disturbance and a generalized seizure associated with multiple legions of cortical and subcortical increased signals including the left posterior lobe, consistent with posterior reversible encephalopathy syndrome (PRES), a condition characterized by headaches, visual disorders, seizures, altered mentation, consciousness disturbances, focal neurological signs, and vasogenic edema predominantly in the white matter of the posterior lobe. Vasoconstriction of the internal carotid artery was undetectable 2 months later, and he was diagnosed as having RCVS. Endothelial dysfunction, associated with impaired TGF-β signaling, might have been attributable to the development of RCVS and PRES. © 2015 Wiley Periodicals, Inc.
Savlan, Ilona; Liakina, Valentina; Valantinas, Jonas
Hepatic encephalopathy is a neuropsychiatric complication of liver cirrhosis the symptoms of which may vary from imperceptible to severe, invaliding, and even lethal. Minimal hepatic encephalopathy is also important because of its tendency to impair patients' cognitive functions and quality of life. The polyetiological pathogenesis of hepatic encephalopathy is intensively studied. A general consensus exists that not only excess of ammonia but also inflammatory, oxidative, and other processes are significant in the development of hepatic encephalopathy.
Patidar, Kavish R; Bajaj, Jasmohan S
The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied, adverse effects (neomycin oto- and nephrotoxicity, metronidazole neurotoxicity) and potential for resistance emergence (vancomycin-resistant enterococcus) has limited the use of most antibiotics, apart from rifaximin which has the greatest evidence base. Rifaximin has also demonstrated, in conjunction with lactulose, to prevent overt HE recurrence in a multi-center, randomized trial. Despite its cost in the US, rifaximin may prove cost-saving by preventing hospitalizations for overt HE. In minimal/covert HE, rifaximin is the only systematically studied antibiotic. Rifaximin showed improvement in cognition, inflammation, quality-of-life and driving simulator performance but cost-analysis does not favor its use at the current time. Antibiotics, especially rifaximin, have a definite role in the management across the spectrum of HE.
McKee, Ann C; Stein, Thor D; Kiernan, Patrick T; Alvarez, Victor E
Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. © 2015 International Society of Neuropathology.
Mahar, Ian; Alosco, Michael L; McKee, Ann C
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder involving cognitive, motor, and psychiatrically-relevant symptoms resulting from repetitive head impacts. Psychiatric phenotypes of CTE, including depression and suicidality, present particular challenges for CTE research, given that the diagnosis requires postmortem neuropathological examination. The pathognomonic lesion of CTE is the perivascular accumulation of hyperphosphorylated tau (ptau) protein at the depths of cortical sulci. These lesions are found in the earliest disease stages, and with advancing pathological severity, ptau deposition occurs in widespread brain regions in a four-stage scheme of severity. We review the psychiatric phenotypes of individuals neuropathologically diagnosed with CTE, and suggest that earlier CTE stages hold particular interest for psychiatric CTE research. In the early CTE stages, there is ptau pathology in frontal cortex and axonal loss in the frontal white matter, followed by progressive ptau neurofibrillary degeneration in the amygdala and hippocampus. Neuropathological changes in the frontal and medial temporal lobes may underlie psychiatric phenotypes. Additional insight into the association between CTE pathology and psychiatric sequelae may come from advancements in in vivo methods of CTE detection. Further epidemiological, clinical, and postmortem studies are needed to validate the nature of psychiatric sequelae in CTE. Copyright © 2017. Published by Elsevier Ltd.
Shintani, Shuzo; Hino, Tarou; Ishihara, Shouichirou; Mizutani, Saneyuki; Shiigai, Tatsuo
We report two cases of reversible brainstem hypertensive encephalopathy (RBHE) with unusual magnetic resonance (MR) findings. Patient 1, an 85-year-old man without a history of hypertension, developed acute severe hypertension and mild consciousness disturbance as the only symptoms. Patient 2, a 46-year-old man with an untreated hypertension, presented with extremely high blood pressure and general fatigue, vertigo, and mild dysarthria as the initial manifestations. In these patients, fluid-attenuated inversion recovery (FLAIR) and T2-weighted MR images revealed diffuse hyperintensities in the brainstem. Diffusion-weighted imaging (DWI) findings were normal, and apparent diffusion coefficient (ADC) values were increased in the brainstem. The supratentorial regions were largely spared, and mildly diffuse hyperintensities were noted in the white matter. There were no accompanying changes in the occipital lobe and cerebellum. The lesions completely resolved after stabilization of blood pressure. The normal DWI findings and high ADC values were consistent with vasogenic edema due to severe hypertension. The characteristics of RBHE are a very high blood pressure, mild clinical and neurologic symptoms, rapidly improved MR findings after initial treatment with the control of hypertension, and a marked clinicoradiologic dissociation.
Wassink, Guido; Gunn, Eleanor R.; Drury, Paul P.; Bennet, Laura; Gunn, Alistair J.
Acute post-asphyxial encephalopathy occurring around the time of birth remains a major cause of death and disability. The recent seminal insight that allows active neuroprotective treatment is that even after profound asphyxia (the “primary” phase), many brain cells show initial recovery from the insult during a short “latent” phase, typically lasting approximately 6 h, only to die hours to days later after a “secondary” deterioration characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Although many of these secondary processes are potentially injurious, they appear to be primarily epiphenomena of the “execution” phase of cell death. Animal and human studies designed around this conceptual framework have shown that moderate cerebral hypothermia initiated as early as possible but before the onset of secondary deterioration, and continued for a sufficient duration to allow the secondary deterioration to resolve, has been associated with potent, long-lasting neuroprotection. Recent clinical trials show that while therapeutic hypothermia significantly reduces morbidity and mortality, many babies still die or survive with disabilities. The challenge for the future is to find ways of improving the effectiveness of treatment. In this review, we will dissect the known mechanisms of hypoxic-ischemic brain injury in relation to the known effects of hypothermic neuroprotection. PMID:24578682
McKee, Ann C.; Stein, Thor D.; Kiernan, Patrick T.; Alvarez, Victor E.
Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43 kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. PMID:25904048
García-Martínez, Rita; Simón-Talero, Macarena; Córdoba, Juan
Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute-on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant. PMID:22045403
Hadjihambi, Anna; Arias, Natalia; Sheikh, Mohammed; Jalan, Rajiv
Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis and/or porto-systemic shunting. The clinical symptoms are widely variable, extending from subtle impairment in mental state to coma. The utility of categorizing the severity of HE accurately and efficiently serves not only to provide practical functional information about the current clinical status of the patient but also gives valuable prognostic information. In the past 20-30 years, there has been rapid progress in understanding the pathophysiological basis of HE; however, the lack of direct correlation between pathogenic factors and the severity of HE make it difficult to select appropriate therapy for HE patients. In this review, we will discuss the classification system and its limitations, the neuropsychometric assessments and their challenges, as well as the present knowledge on the pathophysiological mechanisms. Despite the many prevalent hypotheses around the pathogenesis of the disease, most treatments focus on targeting and lowering the accumulation of ammonia as well as inflammation. However, treatment of minimal HE remains a huge unmet need and a big concerted effort is needed to better define this condition to allow the development of new therapies. We review the currently available therapies and future approaches to treat HE as well as the scientific and clinical data that support their effectiveness.
Jung, Young-Chul; Chanraud, Sandra; Sullivan, Edith V
There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke's encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff's syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.
Grover, Vijay PB; Tognarelli, Joshua M; Massie, Nicolas; Crossey, Mary ME; Cook, Nicola A; Taylor-Robinson, Simon D
Hepatic encephalopathy is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease. It was probably first described by Hippocrates over 2000 years ago, who said that “those whose madness arises from phlegm are quiet and neither shout nor make a disturbance, while those whose madness arises from bile shout, play tricks and will not keep still, but are always up to some mischief ”. He was presumably describing the differences between patients with pneumonia and acute liver failure. Despite the fact that the syndrome was probably first recognized thousands of years ago, the exact pathogenesis still remains unclear. Furthermore, a precise definition of the syndrome is lacking, as are definitive methods of diagnosing this condition. It is important as both patients with cirrhosis and the general population with whom they interact may be affected as a consequence. At a minimum, the individual may be affected by impaired quality of life, impaired ability to work, and slowed reaction times, which are relevant to the population at large if affected individuals operate heavy machinery or drive a car. Pathogenic mechanisms, diagnostic tools, and treatment options are discussed. PMID:26719720
McKee, Ann C.; Alosco, Michael; Huber, Bertrand R.
There are growing concerns that cumulative repetitive head impact exposure through routine participation in contact and collision sports is associated with increased risk of long-term problems in memory and cognition, including the development of chronic traumatic encephalopathy (CTE). CTE is a distinctive neurodegenerative disease that occurs as a result of repetitive head impacts (RHI) including concussion and subconcussion. Like most neurodegenerative diseases, CTE can only be diagnosed by postmortem neuropathologic examination of brain tissue. Recently a panel of exerts concluded that CTE is a unique disorder with a pathognomonic lesion that can be reliably distinguished from other neurodegenerative diseases, such as Alzheimer’s disease and frontotemporal lobar degeneration. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau protein in neurons and astrocytes in an irregular pattern, and is typically most prominent at the depths of the cerebral sulci. Clinically CTE is associated with violent behaviors, explosivity, a loss of control, depression, suicide, memory loss and cognitive changes. While the exact incidence and prevalence of CTE remain unknown, there is increasing evidence that CTE affects amateur atheletes as well as professional athletes and military veterans. Given the millions of contact sport athletes and military service members who are exposed to RHI each year, CTE has become a major public health concern. There is a critical need for identification of CTE during life, improved understanding of the epidemiology and pathobiology, and the development of effective prevention and treatment strategies for CTE. PMID:27637402
Li, Hui; Liu, Xu; Andolina, Ian M; Li, Xiaohong; Lu, Yiliang; Spillmann, Lothar; Wang, Wei
Humans are more sensitive to luminance decrements than increments, as evidenced by lower thresholds and shorter latencies for dark stimuli. This asymmetry is consistent with results of neurophysiological recordings in dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (V1) of cat and monkey. Specifically, V1 population responses demonstrate that darks elicit higher levels of activation than brights, and the latency of OFF responses in dLGN and V1 is shorter than that of ON responses. The removal of a dark or bright disc often generates the perception of a negative afterimage, and here we ask whether there also exist asymmetries for negative afterimages elicited by dark and bright discs. If so, do the poststimulus responses of subcortical ON and OFF cells parallel such afterimage asymmetries? To test these hypotheses, we performed psychophysical experiments in humans and single-cell/S-potential recordings in cat dLGN. Psychophysically, we found that bright afterimages elicited by luminance decrements are stronger and last longer than dark afterimages elicited by luminance increments of equal sizes. Neurophysiologically, we found that ON cells responded to the removal of a dark disc with higher firing rates that were maintained for longer than OFF cells to the removal of a bright disc. The ON and OFF cell asymmetry was most pronounced at long stimulus durations in the dLGN. We conclude that subcortical response strength differences between ON and OFF channels parallel the asymmetries between bright and dark negative afterimages, further supporting a subcortical origin of bright and dark afterimage perception.SIGNIFICANCE STATEMENT Afterimages are physiological aftereffects following stimulation of the eye, the study of which helps us to understand how our visual brain generates visual perception in the absence of physical stimuli. We report, for the first time to our knowledge, asymmetries between bright and dark negative afterimages elicited by
Waked, William J; Gordon, Robert M; Whiteson, Jonathan H; Baron, Erika M
This article reviews the prevalence, underlying mechanisms, and challenges of treating encephalopathy and delirium in the postsurgical and medically compromised cardiopulmonary patient receiving services on an acute inpatient rehabilitation unit. Additionally, pertinent information is provided on conducting an evaluation to assess for neurocognitive sequelae of the above-mentioned conditions to help achieve better treatment outcomes. Review of the medical and neuropsychology literature is provided along with 2 case reports to illustrate evaluation of a persisting toxic-metabolic encephalopathy and a resolving delirium and the treatment team's effectiveness in producing a more optimal treatment outcome. The unique role of the rehabilitation psychologist, special treatment considerations, and the importance of integrated follow-up neurorehabilitation services for the cardiopulmonary patient and caregivers also are emphasized. Encephalopathy and delirium are 2 related, but somewhat different, conditions that can emerge postoperatively, any time during acute care hospitalization, and often enough, during impatient or subacute-care rehabilitation. Their association with long-term harm and poor outcome warrant early identification and immediate medical intervention. Encephalopathy and delirium can significantly affect rehabilitation outcomes and, as such, rehabilitation psychologists are encouraged to systematically screen for the presence of delirium and encephalopathy in the cardiopulmonary rehabilitation setting so to enhance treatment efficacy and quality of life in affected individuals. (c) 2015 APA, all rights reserved).
Kadikoy, Huseyin; Haque, Waqar; Hoang, Vu; Maliakkal, Joseph; Nisbet, John; Abdellatif, Abdul
Posterior reversible encephalopathy syndrome (PRES) is characterized by acute onset of headache, nausea, focal neurological deficits or seizures along with radiological findings of white matter defects in the parietal and occipital lobes. Causes of PRES include uremia, hypertensive encephalopathy, eclampsia and immunosuppressive medications. Usually, the treatment of choice involves correcting the underlying abnormality. We describe an unusual case of recurrent PRES caused by uremia during a lupus flare in a patient with biopsy-proven Class IV Lupus Nephritis (LN) with vasculitis. PRES in systemic lupus erythematosis (SLE) is a rare clinical phenomenon and, when reported, it is associated with hypertensive encephalopathy. Our patient did not have hypertensive crisis, but had uremic encephalopathy. The patient's PRES-related symptoms resolved after initiation of hemodialysis. The temporal correlation of the correction of the uremia and the resolution of the symptoms of PRES show the etiology to be uremic encephalopathy, making this the first reported case of uremia-induced PRES in Class IV LN with vasculitis.
Iacobone, Emanuele; Bailly-Salin, Juliette; Polito, Andrea; Friedman, Diane; Stevens, Robert D; Sharshar, Tarek
Sepsis is often complicated by an acute and reversible deterioration of mental status, which is associated with increased mortality and is consistent with delirium but can also be revealed by a focal neurologic sign. Sepsis-associated encephalopathy is accompanied by abnormalities of electroencephalogram and somatosensory-evoked potentials, increased in biomarkers of brain injury (i.e., neuron-specific enolase, S-100 beta-protein) and, frequently, by neuroradiological abnormalities, notably leukoencephalopathy. Its mechanism is highly complex, resulting from both inflammatory and noninflammatory processes that affect all brain cells and induce blood-brain barrier breakdown, dysfunction of intracellular metabolism, brain cell death, and brain injuries. Its diagnosis relies essentially on neurologic examination that can lead one to perform specific neurologic tests. Electroencephalography is required in the presence of seizure; neuroimaging in the presence of seizure, focal neurologic signs or suspicion of cerebral infection; and both when encephalopathy remains unexplained. In practice, cerebrospinal fluid analysis should be performed if there is any doubt of meningitis. Hepatic, uremic, or respiratory encephalopathy, metabolic disturbances, drug overdose, withdrawal of sedatives or opioids, alcohol withdrawal delirium, and Wernicke's encephalopathy are the main differential diagnoses of sepsis-associated encephalopathy. Patient management is based mainly on controlling infection, organ system failure, and metabolic homeostasis, at the same time avoiding neurotoxic drugs.
Wong-Kisiel, Lily C.; Nickels, Katherine
Epileptic encephalopathy syndromes are disorders in which the epileptiform abnormalities are thought to contribute to a progressive cerebral dysfunction. Characteristic electroencephalogram findings have an important diagnostic value in classification of epileptic encephalopathy syndromes. In this paper, we focus on electroencephalogram findings of childhood epileptic encephalopathy syndromes and provide sample illustrations. PMID:24024028
Lidbury, Jonathan A; Ivanek, Renata; Suchodolski, Jan S; Steiner, Jörg M
To elucidate the relationship between plasma ammonia concentration and severity of hepatic encephalopathy and determine whether factors that precipitate hepatic encephalopathy in humans are associated with the presence of clinical signs of hepatic encephalopathy in dogs previously treated for the disease. Retrospective case series. 118 dogs with hepatic encephalopathy. The medical records database of a veterinary teaching hospital was searched for records of dogs in which hepatic encephalopathy was diagnosed between October 1, 1991, and September 1, 2014. Hepatic encephalopathy severity was graded on a 5-point scale, and the correlation between disease severity and plasma ammonia concentration was determined. Respective associations between hepatic encephalopathy and systemic inflammatory response syndrome, gastrointestinal hemorrhage, dietary indiscretion, constipation, furosemide treatment, azotemia, hypokalemia, hyponatremia, alkalosis, and hyperammonemia were assessed by Fisher exact tests followed by multivariable logistic regression. Severity of hepatic encephalopathy at hospital admission was not significantly correlated with plasma ammonia concentration. Dogs treated for hepatic encephalopathy prior to hospital admission were significantly less likely to have clinical signs of the disease at hospital admission, compared with dogs that were not treated for the disease (OR, 0.36; 95% confidence interval, 0.17 to 0.78). None of the putative precipitating factors for hepatic encephalopathy were significantly associated with the presence of clinical signs of the disease at hospital admission. Results indicated that hepatic encephalopathy treatment alleviated clinical signs of the disease. Further investigation is necessary to identify precipitating factors for hepatic encephalopathy in dogs.
... Conditions SCN8A-related epilepsy with encephalopathy SCN8A-related epilepsy with encephalopathy Printable PDF Open All Close All ... view the expand/collapse boxes. Description SCN8A -related epilepsy with encephalopathy is a condition characterized by recurrent ...
Horton, Nicholas G.; Wang, Ke; Kobat, Demirhan; Clark, Catharine G.; Wise, Frank W.; Schaffer, Chris B.; Xu, Chris
Two-photon fluorescence microscopy enables scientists in various fields including neuroscience, embryology and oncology to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of two-photon fluorescence microscopy to the cortical layer within mouse brain, and imaging subcortical structures currently requires the removal of overlying brain tissue or the insertion of optical probes. Here, we demonstrate non-invasive, high-resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein-labelled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher-order nonlinear excitation overcomes the limitations of two-photon fluorescence microscopy, enabling biological investigations to take place at a greater depth within tissue.
Kleinschmidt, Andreas; Rusconi, Elena
That disconnection causes clinical symptoms is a very influential concept in behavioral neurology. Criteria for subcortical disconnection usually are symptoms that are distinct from those following cortical lesions and damage to a single, long-range fiber tract. Yet, a recent study combining functional magnetic resonance imaging and fiber tracking concluded that a focal lesion in left parietal white matter provides the only tenable explanation for pure Gerstmann's syndrome, an enigmatic tetrad of acalculia, agraphia, finger agnosia, and left-right disorientation. Such a lesion would affect not only a single fiber tract but crossing or "kissing" of different fiber tracts and hence disconnect separate cortical networks. As fiber crossing is prominent in the cerebral white matter, the authors propose an extension to the subcortical disconnection framework that opens the door to ascribing a more diversified clinical phenomenology to white matter damage and ensuing disconnection than has been the case so far.
Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Yao, Yin; Ho, Yvonne Y W; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F
Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.
Kwon, Mijung; Bagonis, Maria; Danuser, Gaudenz; Pellman, David
SUMMARY Positioning of centrosomes is vital for cell division and development. In metazoan cells, spindle positioning is controlled by a dynamic pool of subcortical actin that organizes in response to the position of retraction fibers. These actin “clouds” are proposed to generate pulling forces on centrosomes and mediate spindle orientation. However, the motors that pull astral microtubules toward these actin structures are not known. Here, we report that the unconventional myosin, Myo10, couples actin-dependent forces from retraction fibers and subcortical actin clouds to centrosomes. Myo10-mediated centrosome positioning requires its direct microtubule binding. Computational image analysis of large microtubule populations reveals a direct effect of Myo10 on microtubule dynamics and microtubule-cortex interactions. Myo10’s role in centrosome positioning is distinct from, but overlaps with, that of dynein. Thus, Myo10 plays a key role in integrating the actin and microtubule cytoskeletons to position centrosomes and mitotic spindles. PMID:26235048
Heller, Aaron S.
Depression is a debilitating disorder causing significant societal and personal suffering. Improvements in identification of major depressive disorder (MDD) and its treatment are essential to reduce its toll. Recent developments in rodent models of MDD and neuroimaging of humans suffering from the disorder provide avenues through which gains can be made towards reducing its burden. In this review, new findings, integrating across rodent models and human imaging are highlighted that have yielded new insights towards a basic understanding of the disorder. In particular, this review focuses on cortical-subcortical interactions underlying the pathophysiology of MDD. In particular, evidence is accruing that dysfunction in prefrontal-subcortical circuits including the amygdala, ventral striatum (VS), hippocampus and dorsal raphe nucleus (DRN) are associated with MDD status. PMID:27013988
Eisner, W; Burtscher, J; Bale, R; Sweeney, R; Koppelstatter, F; Golaszewski, S; Kolbitsch, C; Twerdy, K
Objectives: Subcortical lesions in the sensorimotor strip are often considered to be inoperable. The purpose of this study was to evaluate the usefulness of a combined approach for surgery in this region, aided by a robotic neuronavigation system under electrophysiological control. Methods: In a prospective study on 10 patients, space occupying lesions in the sensorimotor central area were removed using the Surgiscope® robotic navigation system and the Nicolet Viking IV® electrophysiological system. Results: Precise tumour localisation with the neuronavigation system and the information on the patient's cortical motor distribution obtained by bipolar cortical stimulation led to postoperative improvement in motor function in all but one patient. Seven of the patients had focal, defined pathology (four metastases; two cavernoma; one aspergilloma). Conclusion: Due to the implementation of two recent technologies, surgery of lesions in the subcortical sensorimotor region can be performed with greater confidence. PMID:11861700
Strait, Dana L; Kraus, Nina; Skoe, Erika; Ashley, Richard
Musicians exhibit enhanced perception of emotion in speech, although the biological foundations for this advantage remain unconfirmed. In order to gain a better understanding for the influences of musical experience on neural processing of emotionally salient sounds, we recorded brainstem potentials to affective human vocal sounds. Musicians showed enhanced time-domain response magnitude to the most spectrally complex portion of the stimulus and decreased magnitude to the more periodic, less complex portion. Enhanced phase-locking to stimulus periodicity was likewise seen in musicians' responses to the complex portion. These results suggest that auditory expertise engenders both enhancement and efficiency of subcortical neural responses that are intricately connected with acoustic features important for the communication of emotional states. Our findings provide the first biological evidence for behavioral observations indicating that musical training enhances the perception of vocally expressed emotion in addition to establishing a subcortical role in the auditory processing of emotional cues.
Patidar, Kavish R; Bajaj, Jasmohan S
Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into 2 broad categories based on severity: covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE). CHE has a significant impact on a patient's quality of life, driving performance, and recently has been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, early diagnosis and management are imperative. In addition, focus also should be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of nonabsorbable disaccharides, antibiotics (ie, rifaximin), and, potentially, probiotics. Other therapies currently under further investigation include L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion.
Kapina, Viktoria; Vargas, Maria-Isabel; Wohlrab, Gabriele; Vulliemoz, Serge; Fluss, Joel; Seeck, Margitta
Chronic epilepsy has rarely been reported after posterior reversible encephalopathy syndrome (PRES) and the association with hippocampal sclerosis has been suggested only once before. We report the case of a girl admitted at the age of 8 years with idiopathic nephrotic syndrome. On the second day of admission, she presented with focal complex seizures and cerebral MRI showed posterior encephalopathy and no hippocampal sclerosis. MRI after one month confirmed the diagnosis of PRES. The seizures recurred and the girl developed pharmacoresistant epilepsy and was admitted to our hospital for further investigation. Cerebral MRI three years after the diagnosis of PRES showed hippocampal sclerosis which was not present on the initial MRI. We conclude that there is a triggering role of PRES in the development of hippocampal sclerosis. Hippocampal sclerosis may have resulted from seizure-associated damage, alternatively, hypertensive encephalopathy may have led to hippocampal damage via a vascular mechanism.
Ebringer, Alan; Rashid, Taha; Wilson, Clyde
"Bovine spongiform encephalopathy", "scrapie", as well as Creutzfeldt-Jakob disease and kuru belong to a group of related neurological conditions termed "transmissible spongiform encephalopathies". These diseases are based on the LD50 measurement whereby saline brain homogenates are injected into experimental animals and when 50% of them develop symptoms, this is considered as transmission of the disease, but the gold standard for diagnosis is autopsy examination. However, an untenable assumption is being made in that saline brain homogenates do not cause tissue damage but it is known since the time of Pasteur, that they give rise to "post-rabies vaccination allergic encephalomyelitis". This is the fundamental flaw in the diagnosis of these diseases. A way forward, however, is to examine infectious agents, such as Acinetobacter which show molecular mimicry with myelin and elevated levels of antibodies to this microbe are found in multiple sclerosis patients and animals affected by "bovine spongiform encephalopathy".
Gul Mert, Gülen; Horoz, Ozden Ozgur; Herguner, M Ozlem; Incecik, Faruk; Yildizdas, R Dincer; Onenli Mungan, Neslihan; Yuksel, Bilgin; Altunbasak, Sakir
Hashimoto's encephalopathy is a rare clinically heterogenous condition consisting of encephalopathy, seizures and variable neurological and psychiatric manifestations, accompanied by high titres of serum antithyroid antibodies. We described the clinical and laboratory findings of four children (aged 8-17 years) with Hashimoto's encephalopathy. The clinical features of three patients at presentation included refractory epilepsy, and confusion, and one patient presented with behavioral and cognitive changes. During their presentation, two of them were in euthyroid, and the others were in hypothyroid status. All patients manifested increased antithyroid antibodies. Two patients improved with steroid treatment. The others responded to plasmapheresis instead of corticosteroid treatment. Physicians' awareness of this complication is of great importance because most patients respond dramatically to the treatment.
Pera, Maria Carmela; Randazzo, Giovanna; Masnada, Silvia; Dontin, Serena Donetti; De Giorgis, Valentina; Balottin, Umberto; Veggiotti, Pierangelo
The aim of this retrospective study of children affected by epileptic encephalopathy was to evaluate seizure frequency, electroencephalographic pattern and neuropsychological status, before and after intravenous methylprednisolone therapy. Eleven children with epileptic encephalopathy were administered one cycle of intravenous methylprednisolone (15-30 mg/kg/day for three consecutive days, once a month for four months) in addition to constant dosages of their regular antiepileptic drugs. The treatment resulted in statistically significant reductions of generalized slow spike-and-wave discharges (p<0.0028) and seizure frequency (p<0.013), which persisted even after methylprednisolone pulse therapy was stopped. A globally positive outcome was noted in 9/11 patients (81.8%). This methylprednisolone treatment regimen did not cause significant or persistent adverse effects. We suggest that children with epileptic encephalopathy without an underlying structural lesion could be the best candidates for intravenous methylprednisolone pulse therapy.
Torre Delgadillo, Aldo; Guerrero-Hernández, Ignacio; Uribe, Misael
The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. This cirrhosis complication is generally not perceived by physician, and diagnosis can only be made by neuropsychological tests and other especial measurements like evoked potentials and image studies like positron emission tomography. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.
Rath, Amitav; Naryanan, T Jaishree; Chowdhary, G V S; Murthy, J M K
Hyperammonemic encephalopathy with normal liver function is an uncommon serious adverse effect of valproate therapy. We retrospectively analyzed the case records of 5 patients of epilepsy on valproate with hyperammonemic encephalopathy. Of the 5 patients, 3 were on monotherapy. The mean valproate dose was 1250 mg/day and the duration of therapy ranged between 4 and 90 days. Alteration in the sensorium was the presenting clinical feature. The risk factors included high initial dose (2), long-term valproate therapy (1), and long-term valproate therapy with concomitant topiramate (1). There was good correlation between the fall in serum ammonia levels and clinical improvement. Hyperammonemic encephalopathy should be suspected in patients on valproate with altered sensorium. Response to treatment is rewarding.
An intimate link exists between the predictive and learning processes in the brain. Perceptual/cognitive and spatial/motor processes use complementary predictive mechanisms to learn, recognize, attend and plan about objects in the world, determine their current value, and act upon them. Recent neural models clarify these mechanisms and how they interact in cortical and subcortical brain regions. The present paper reviews and synthesizes data and models of these processes, and outlines a unified theory of predictive brain processing. PMID:19528003
Introduction The neuronal loss in Alzheimer disease (AD) has been described to affect grey matter in the cerebral cortex. However, in the elderly, AD pathology is likely to occur together with subcortical axonal degeneration on the basis of cerebrovascular disease. Therefore, we hypothesized that biomarkers for AD and subcortical axonal degeneration would correlate in patients undergoing testing for dementia biomarkers, particularly in older age groups. Methods We performed correlation and cluster analyses of cerebrospinal fluid (CSF) biomarker data from 5,542 CSF samples analyzed in our routine clinical neurochemistry laboratory in 2010 through 2012 for the established CSF AD biomarkers total tau (T-tau), phosphorylated-tau (P-tau), amyloid β1-42 (Aβ42), and for neurofilament light (NFL), which is a protein expressed in large-caliber myelinated axons, the CSF levels of which correlate with subcortical axonal injury. Results Aβ42, T-tau, and P-tau correlated with NFL. By cluster analysis, we found a bimodal data distribution in which a group with a low Aβ42/P-tau ratio (suggesting AD pathology) had high levels of NFL. High levels of NFL also correlated with the presence of an AD biomarker pattern defined by Aβ42/P-tau and T-tau. Only 29% of those with an AD biomarker signature had normal NFL levels. Age was a possible confounding factor for the associations between NFL and established AD biomarkers, but in a logistic regression analysis, both age and NFL independently predicted the AD biomarker pattern. Conclusions The association between an AD-like signature using the established biomarkers Aβ42, T-tau, and P-tau with increased levels of NFL provides in vivo evidence of an association between AD and subcortical axonal degeneration in this uniquely large dataset of CSF samples tested for dementia biomarkers. PMID:24479774
Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E
Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Mao, Cui Ping; Bai, Zhi Lan; Zhang, Xiao Na; Zhang, Qiu Juan; Zhang, Lei
Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high-resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB’s integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID:26834629
Rifai, Z; Klitzke, M; Tawil, R; Kazee, A M; Shanske, S; DiMauro, S; Griggs, R C
To characterize the dementia associated with adult polyglucosan body disease (APBD) and to correlate the cognitive deficits with abnormalities found on magnetic resonance imaging (MRI). Quantitative neuropsychological testing and MRI in one man with APBD and a review of the literature. The dementia of APBD affects cortical and subcortical functions. The cognitive deficits correlate with MRI findings of cortical atrophy and white-matter abnormalities. Neuropsychological testing and MRI are helpful in the evaluation of patients with APBD.
Radman, Narges; Cacioppo, Stephanie; Spierer, Lucas; Schmidlin, Eric; Mayer, Eugène; Annoni, Jean-Marie
The supplementary motor area (SMA) plays a key role in motor programming and production and is involved in internally-cued movements. In neurological populations, SMA syndrome following a lesion to the "SMA proper" is characterized by transient impairment of voluntary movements and motor sequences. This syndrome is assumed to follow on from an interruption of the motor cortico-subcortical loop, and some case reports indicate that such a syndrome could occur after a brain lesion isolating the SMA from subcortical structures. To characterize the pattern of motor impairments in a patient whose stroke disconnects the SMA from the subcortical motor loop. A patient developed a moderate transient left hemiparesis following a subcortical stroke in the right anterior cerebral artery area, which disconnected the SMA from basal ganglia. Eight days after the stroke, when the hemiparesis had regressed, the patient presented a specific SMA motor disorder of the left hand which manifested as an akinesia and was exacerbated when his visual attention was not directed towards his hand. We assessed finger tapping with left and right hands, eyes closed and open, in the left and right hemispace. We indexed movement speed as the number of taps filmed over 5-s periods. Left motor weakness (grasping strength of right hand: 49 kg and left hand: 41 kg) was resolved in a week. Ideomotor and ideational gestures and motor sequences were preserved. On the tapping task, left-hand tapping was slower than right-hand tapping. Critically, visual feedback improved tapping speed for the left, but not for the right, hand. The hemispace of the task execution had no effect on tapping performance. Our results suggest that SMA-basal ganglia disconnection decreases contralateral movement initiation and maintenance and this effect is partly compensated by visual cues. Copyright © 2013 Elsevier Ltd. All rights reserved.
Guadalupe, Tulio; Zwiers, Marcel P; Teumer, Alexander; Wittfeld, Katharina; Vasquez, Alejandro Arias; Hoogman, Martine; Hagoort, Peter; Fernandez, Guillen; Buitelaar, Jan; Hegenscheid, Katrin; Völzke, Henry; Franke, Barbara; Fisher, Simon E; Grabe, Hans J; Francks, Clyde
Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10(-8) ). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries.
Lucke-Wold, Brandon P; Turner, Ryan C; Logsdon, Aric F; Nguyen, Linda; Bailes, Julian E; Lee, John M; Robson, Matthew J; Omalu, Bennet I; Huber, Jason D; Rosen, Charles L
Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3β. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.
Reschetniak, V K; Kukushkin, M L; Gurko, N S
This review presents the current data in the literature about the importance of the cortex and subcortical structures of the brain in the perception of acute and chronic pain. Discussed the importance of various areas of the brain in perception discriminative and affective components of pain. Discusses also gender differences in pain perception depending on the functional activity of brain cortex and antinociceptive subcortical structures. Analyzed the morphological changes of cortical and subcortical structures of the brain in chronic pain syndromes. It is proved that the decrease in the volume of gray and white matter of cerebral cortex and subcortical structures is a consequence and not the cause of chronic pain syndrome. Discusses the features activate and deactivate certain areas of the cortex of the brain in acute and chronic pain. Analyzed same features the activation of several brain structures in migraine and cluster headache.
Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sara; Miller, Rachel; Tossell, Julia W.; Vyas, Nora S.; Stidd, Reva; David, Christopher; Gogtay, Nitin
Background: Progressive cortical gray matter (GM) abnormalities are an established feature of schizophrenia and are more pronounced in rare, severe, and treatment refractory childhood-onset schizophrenia (COS) cases. The effect of sex on brain development in schizophrenia is poorly understood and studies to date have produced inconsistent results. >Methods: Using the largest to date longitudinal sample of COS cases (n = 104, scans = 249, Male/Female [M/F] = 57/47), we compared COS sex differences with sex differences in a sample of matched typically developing children (n = 104, scans = 244, M/F = 57/47), to determine whether or not sex had differential effects on cortical and subcortical brain development in COS. Results: Our results showed no significant differential sex effects in COS for either GM cortical thickness or subcortical volume development (sex × diagnosis × age interaction; false discovery rate q = 0.05). Conclusion: Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children. PMID:21613381
Wager, Tor D.; Davidson, Matthew L.; Hughes, Brent L.; Lindquist, Martin A.; Ochsner, Kevin N.
Although prefrontal cortex has been implicated in the cognitive regulation of emotion, the cortical-subcortical interactions that mediate this ability remain poorly understood. To address this issue, we identified a right ventrolateral prefrontal region (vlPFC) whose activity correlated with reduced negative emotional experience during cognitive reappraisal of aversive images. We then applied a novel pathway-mapping analysis on subcortical regions to locate mediators of the association between vlPFC activity and reappraisal success (i.e. reductions in reported emotion). Results identified two separable pathways that together explained ~50% of the reported variance in self-reported emotion: 1) a path through nucleus accumbens that predicted greater reappraisal success, and 2) a path through ventral amygdala that predicted reduced reappraisal success (i.e., more negative emotion). These results provide direct evidence that vlPFC is involved in both the generation and regulation of emotion through different subcortical pathways, suggesting a general role for this region in appraisal processes. PMID:18817740
Vossler, D G; Lee, J K; Ko, T S
Focal and generalized cortical dysgeneses are sometimes seen on the magnetic resonance images (MRI) of patients with epilepsy. Subcortical laminar heterotopia are bilateral collections of gray matter in the centrum semiovale that resemble a band or "double cortex" on MRI. We studied one male and two female patients with subcortical laminar heterotopia who had moderate to severe developmental delay, early-onset epilepsy, and medically refractory seizures. Atonic, atypical absence, tonic, myoclonic, complex partial, and generalized tonic-clonic seizures were recorded. Interictal and ictal electroencephalographic patterns were generalized and, less commonly, multifocal. Two years after corpus callosotomy, one patient was free of generalized tonic-clonic and atonic seizures, but the other patient who had undergone callosotomy had no significant reduction in seizure frequency. With lamotrigine treatment, the patient who had not had surgery had complete cessation of monthly episodes of status epilepticus and a dramatic reduction of generalized tonic-clonic seizures, and the other patient who received lamotrigine had a 50% reduction of her atonic seizures. In patients with subcortical laminar heterotopia, atonic and generalized tonic-clonic seizures can be substantially reduced or eliminated by corpus callosotomy or treatment with lamotrigine.
Dogonowski, Anne-Marie; Siebner, Hartwig R; Sørensen, Per Soelberg; Wu, Xingchen; Biswal, Bharat; Paulson, Olaf B; Dyrby, Tim B; Skimminge, Arnold; Blinkenberg, Morten; Madsen, Kristoffer H
Multiple sclerosis (MS) impairs signal transmission along cortico-cortical and cortico-subcortical connections, affecting functional integration within the motor network. Functional magnetic resonance imaging (fMRI) during motor tasks has revealed altered functional connectivity in MS, but it is unclear how much motor disability contributed to these abnormal functional interaction patterns. To avoid any influence of impaired task performance, we examined disease-related changes in functional motor connectivity in MS at rest. A total of 42 patients with MS and 30 matched controls underwent a 20-minute resting-state fMRI session at 3 Tesla. Independent component analysis was applied to the fMRI data to identify disease-related changes in motor resting-state connectivity. Patients with MS showed a spatial expansion of motor resting-state connectivity in deep subcortical nuclei but not at the cortical level. The anterior and middle parts of the putamen, adjacent globus pallidus, anterior and posterior thalamus and the subthalamic region showed stronger functional connectivity with the motor network in the MS group compared with controls. MS is characterised by more widespread motor connectivity in the basal ganglia while cortical motor resting-state connectivity is preserved. The expansion of subcortical motor resting-state connectivity in MS indicates less efficient funnelling of neural processing in the executive motor cortico-basal ganglia-thalamo-cortical loops.
Roshchupkin, Gennady V.; Gutman, Boris A.; Vernooij, Meike W.; Jahanshad, Neda; Martin, Nicholas G.; Hofman, Albert; McMahon, Katie L.; van der Lee, Sven J.; van Duijn, Cornelia M.; de Zubicaray, Greig I.; Uitterlinden, André G.; Wright, Margaret J.; Niessen, Wiro J.; Thompson, Paul M.; Ikram, M. Arfan; Adams, Hieab H. H.
The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures. PMID:27976715
Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sara; Miller, Rachel; Tossell, Julia W; Vyas, Nora S; Stidd, Reva; David, Christopher; Gogtay, Nitin
Progressive cortical gray matter (GM) abnormalities are an established feature of schizophrenia and are more pronounced in rare, severe, and treatment refractory childhood-onset schizophrenia (COS) cases. The effect of sex on brain development in schizophrenia is poorly understood and studies to date have produced inconsistent results. Using the largest to date longitudinal sample of COS cases (n = 104, scans = 249, Male/Female [M/F] = 57/47), we compared COS sex differences with sex differences in a sample of matched typically developing children (n = 104, scans = 244, M/F = 57/47), to determine whether or not sex had differential effects on cortical and subcortical brain development in COS. Our results showed no significant differential sex effects in COS for either GM cortical thickness or subcortical volume development (sex × diagnosis × age interaction; false discovery rate q = 0.05). Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children.
Kang, Jiyoung; Pae, Chongwon; Park, Hae-Jeong
The configuration of the human brain system at rest, which is in a transitory phase among multistable states, remains unknown. To investigate the dynamic systems properties of the human brain at rest, we constructed an energy landscape for the state dynamics of the subcortical brain network, a critical center that modulates whole brain states, using resting state fMRI. We evaluated alterations in energy landscapes following perturbation in network parameters, which revealed characteristics of the state dynamics in the subcortical brain system, such as maximal number of attractors, unequal temporal occupations, and readiness for reconfiguration of the system. Perturbation in the network parameters, even those as small as the ones in individual nodes or edges, caused a significant shift in the energy landscape of brain systems. The effect of the perturbation on the energy landscape depended on the network properties of the perturbed nodes and edges, with greater effects on hub nodes and hubs-connecting edges in the subcortical brain system. Two simultaneously perturbed nodes produced perturbation effects showing low sensitivity in the interhemispheric homologous nodes and strong dependency on the more primary node among the two. This study demonstrated that energy landscape analysis could be an important tool to investigate alterations in brain networks that may underlie certain brain diseases, or diverse brain functions that may emerge due to the reconfiguration of the default brain network at rest. Copyright © 2017 Elsevier Inc. All rights reserved.
Maggu, Akshay R.; Liu, Fang; Antoniou, Mark; Wong, Patrick C. M.
Across time, languages undergo changes in phonetic, syntactic, and semantic dimensions. Social, cognitive, and cultural factors contribute to sound change, a phenomenon in which the phonetics of a language undergo changes over time. Individuals who misperceive and produce speech in a slightly divergent manner (called innovators) contribute to variability in the society, eventually leading to sound change. However, the cause of variability in these individuals is still unknown. In this study, we examined whether such misperceptions are represented in neural processes of the auditory system. We investigated behavioral, subcortical (via FFR), and cortical (via P300) manifestations of sound change processing in Cantonese, a Chinese language in which several lexical tones are merging. Across the merging categories, we observed a similar gradation of speech perception abilities in both behavior and the brain (subcortical and cortical processes). Further, we also found that behavioral evidence of tone merging correlated with subjects' encoding at the subcortical and cortical levels. These findings indicate that tone-merger categories, that are indicators of sound change in Cantonese, are represented neurophysiologically with high fidelity. Using our results, we speculate that innovators encode speech in a slightly deviant neurophysiological manner, and thus produce speech divergently that eventually spreads across the community and contributes to sound change. PMID:28066218
Lamar, Melissa; Price, Cate C; Giovannetti, Tania; Swenson, Rod; Libon, David J
The introduction of diagnostic criteria for vascular dementia has helped to re-define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes.
Guadalupe, Tulio; Mathias, Samuel R; vanErp, Theo G M; Whelan, Christopher D; Zwiers, Marcel P; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A; Arias-Vásquez, Alejandro; Aribisala, Benjamin S; Armstrong, Nicola J; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E; Baune, Bernhard T; Blangero, John; Bokde, Arun L W; Boedhoe, Premika S W; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Büchel, Christian; Buitelaar, Jan; Calhoun, Vince D; Cannon, Dara M; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; de Zubicaray, Greig I; de Zwarte, Sonja M C; Deary, Ian J; Desrivières, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dørum, Erlend S; Ehrlich, Stefan; Espeseth, Thomas; Fernández, Guillén; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jürgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U; Heinz, Andreas; Hibar, Derrek P; Hoekstra, Pieter J; Hoogman, Martine; Howells, Fleur M; Hu, Hao; Hulshoff Pol, Hilleke E; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jönsson, Erik G; Jurk, Sarah; Kahn, Rene S; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L; Medland, Sarah E; Menchón, José M; Morris, Derek W; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C; Nees, Frauke; Nordvik, Jan E; Onnink, A Marten H; Opel, Nils; Ophoff, Roel; Paillère Martinot, Marie-Laure; Papadopoulos Orfanos, Dimitri; Pauli, Paul; Paus, Tomáš; Poustka, Luise; Reddy, Janardhan Yc; Renteria, Miguel E; Roiz-Santiáñez, Roberto; Roos, Annerine; Royle, Natalie A; Sachdev, Perminder; Sánchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N; Soares, Jair C; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Toro, Roberto; Turner, Jessica A; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernández, Maria Valdés; van den Heuvel, Odile A; van der Meer, Dennis; van Haren, Neeltje E M; Veltman, Dick J; Venkatasubramanian, Ganesan; Vetter, Nora C; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M; Glahn, David C; Mazoyer, Bernard; Fisher, Simon E; Francks, Clyde
The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.
Scranton, Robert A; Fung, Steve H; Britz, Gavin W
Cavernomas comprise 8%-15% of intracranial vascular lesions, usually supratentorial in location and superficial. Cavernomas in the thalamus or subcortical white matter represent a unique challenge for surgeons in trying to identify and then use a safe corridor to access and resect the pathology. Previous authors have described specific open microsurgical corridors based on pathology location, often with technical difficulty and morbidity. This series presents 2 cavernomas that were resected using a minimally invasive approach that is less technically demanding and has a good safety profile. The authors report 2 cases of cavernoma: one in the thalamus and brainstem with multiple hemorrhages and the other in eloquent subcortical white matter. These lesions were resected through a transulcal parafascicular approach with a port-based minimally invasive technique. In this series there was complete resection with no neurological complications. The transulcal parafascicular minimally invasive approach relies on image interpretation and trajectory planning, intraoperative navigation, cortical cannulation and subcortical space access, high-quality optics, and resection as key elements to minimize exposure and retraction and maximize tissue preservation. The authors applied this technique to 2 patients with cavernomas in eloquent locations with excellent outcomes.
Guelsoy, Murat; Celikel, Tansu; Kurtkaya, Ozlem; Sav, Aydin; Kurt, Adnan; Canbeyli, Resit; Cilesiz, Inci F.
The use of 980 nm diode laser irradiation within cortical tissue was investigated by the author's previous work. In the present study the lesions created in cortical and subcortical tissues and lesioning effects of diode laser applied in continuous and pulsed regimes were compared. In vivo stereotaxic neurosurgical procedure was performed on female Wistar rats' cortical and subcortical tissues. 980 nm diode laser was applied in two different regimes, cw and pulsed wave respectively. Lesion dimensions were measured and compared. The lasing parameters were found suitable for both brain regions. No significant difference was found between tissues. Lesions diameters varied in the range of 1.0-9.0 mm. Histological examination revealed data for a limited thermal damage in the surrounding tissue for all lesions. Cortical and subcortical tissues did not show significant differences due to same amount of energy delivered. The lasing regime did not influence the dimensions of lesions. Applied energy was found the key element determining the amount of lesion. Results were consistent with the findings found in the previous dosimetry studies.
Melloni, Margherita; Sedeño, Lucas; Hesse, Eugenia; García-Cordero, Indira; Mikulan, Ezequiel; Plastino, Angelo; Marcotti, Aida; López, José David; Bustamante, Catalina; Lopera, Francisco; Pineda, David; García, Adolfo M.; Manes, Facundo; Trujillo, Natalia; Ibáñez, Agustín
Impairments of action language have been documented in early stage Parkinson’s disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies. PMID:26152329
Leunissen, Inge; Coxon, James P; Caeyenberghs, Karen; Michiels, Karla; Sunaert, Stefan; Swinnen, Stephan P
Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico-subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract-based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico-subcortical loops with the (pre-)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal-subcortical projections in TBI, which is associated with task switching impairments.
Zhang, Yong; Li, Kuang-Shi; Ning, Yan-Zhe; Fu, Cai-Hong; Liu, Hong-Wei; Han, Xiao; Cui, Fang-Yuan; Ren, Yi; Zou, Yi-Huai
Abstract A large number of functional imaging studies have focused on the understanding of motor-related neural activities after ischemic stroke. However, the knowledge is still limited in the structural and functional changes of the interhemispheric connections of the bilateral primary motor cortices (M1s) and their potential influence on motor function recovery following stroke. Twenty-four stroke patients with right hemispheric subcortical infarcts and 25 control subjects were recruited to undergo multimodal magnetic resonance imaging examinations. Structural impairments between the bilateral M1s were measured by fractional anisotropy. Functional changes of the bilateral M1s were assessed via M1-M1 resting-state functional connectivity. Task-evoked activation analysis was applied to identify the roles of the bilateral hemispheres in motor function recovery. Compared with control subjects, unilateral subcortical stroke patients revealed significantly decreased fractional anisotropy and functional connectivity between the bilateral M1s. Stroke patients also revealed higher activations in multiple brain regions in both hemispheres and that more regions were located in the contralesional hemisphere. This study increased our understanding of the structural and functional alterations between the bilateral M1s that occur in unilateral subcortical stroke and provided further evidence for the compensatory role played by the contralesional hemisphere for these alterations during motor function recovery. PMID:27495109
Lidbury, Jonathan A; Cook, Audrey K; Steiner, Jörg M
To comparatively review the pathogenesis, clinical presentation, diagnosis, and management of hepatic encephalopathy (HE) in dogs and cats. The Medline database was searched for articles related to HE in people, dogs, and cats. Articles published within the last 5 years were given special importance. The pathogenesis of HE is complex and incompletely understood, but ammonia appears to play a central role. Hyperammonemia leads to accumulation of glutamine in astrocytes, with subsequent astrocyte swelling and neurological dysfunction. The development of HE in patients with hepatic cirrhosis is a poor prognostic indicator. The fermentable disaccharide lactulose and the antimicrobial rifaximin are US Food and Drug Administration approved treatments for human HE. Severe protein restriction is no longer recommended for patients with this condition. HE is often associated with portosystemic shunting in dogs and cats. Ammonia plays a central role in the pathogenesis of HE in dogs and cats, but other factors such as manganese and endogenous benzodiazepines may also contribute. Recently, a soy protein-based diet was found to be beneficial in treating canine HE. Severe dietary protein restriction is likely to be detrimental in affected animals. There have been no clinical trials of drugs routinely used in the management HE in veterinary medicine, but lactulose and antimicrobials such as metronidazole are well-established treatments. HE is a potentially life-threatening condition that is probably underdiagnosed in companion animals. Although various treatment recommendations have been proposed, there is a lack of evidence in the veterinary literature regarding optimal strategies for the management of this condition. As our understanding of the pathogenesis of HE in dogs and cats evolves, novel diagnostic tests and therapeutic agents may become available. © Veterinary Emergency and Critical Care Society 2016.
Hua, Cong; Ju, Wei-Na; Jin, Hang; Sun, Xin; Zhao, Gang
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In this review, we
Hua, Cong; Ju, Wei-na; Jin, Hang; Sun, Xin; Zhao, Gang
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to