High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

PubMed

Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

2018-01-01

Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

Myoclonic Jerks and Schizophreniform Syndrome: Case Report and Literature Review.

PubMed

Endres, Dominique; Altenmüller, Dirk-M; Feige, Bernd; Maier, Simon J; Nickel, Kathrin; Hellwig, Sabine; Rausch, Jördis; Ziegler, Christiane; Domschke, Katharina; Doerr, John P; Egger, Karl; Tebartz van Elst, Ludger

2018-01-01

Background: Schizophreniform syndromes can be divided into primary idiopathic forms as well as different secondary organic subgroups (e.g., paraepileptic, epileptic, immunological, or degenerative). Secondary epileptic explanatory approaches have often been discussed in the past, due to the high rates of electroencephalography (EEG) alterations in patients with schizophrenia. In particular, temporal lobe epilepsy is known to be associated with schizophreniform symptoms in well-described constellations. In the literature, juvenile myoclonic epilepsy has been linked to emotionally unstable personality traits, depression, anxiety, and executive dysfunction; however, the association with schizophrenia is largely unclear. Case presentation: We present the case of a 28-year-old male student suffering from mild myoclonic jerks, mainly of the upper limbs, as well as a predominant paranoid-hallucinatory syndrome with attention deficits, problems with working memory, depressive-flat mood, reduced energy, fast stimulus satiation, delusional and audible thoughts, tactile hallucinations, thought inspirations, and severe sleep disturbances. Cerebral magnetic resonance imaging and cerebrospinal fluid analyses revealed no relevant abnormalities. The routine EEG and the first EEG after sleep deprivation (under treatment with oxazepam) also returned normal findings. Video telemetry over one night, which included a partial sleep-deprivation EEG, displayed short generalized spike-wave complexes and polyspikes, associated with myoclonic jerks, after waking in the morning. Video-EEG monitoring over 5 days showed over 100 myoclonic jerks of the upper limbs, frequently with generalized spike-wave complexes with left or right accentuation. Therefore, we diagnosed juvenile myoclonic epilepsy. Discussion: This case report illustrates the importance of extended EEG diagnostics in patients with schizophreniform syndromes and myoclonic jerks. The schizophreniform symptoms in the framework of

Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study.

PubMed

Vollmar, Christian; O'Muircheartaigh, Jonathan; Barker, Gareth J; Symms, Mark R; Thompson, Pamela; Kumari, Veena; Duncan, John S; Janz, Dieter; Richardson, Mark P; Koepp, Matthias J

2011-06-01

Juvenile myoclonic epilepsy is the most frequent idiopathic generalized epilepsy syndrome. It is characterized by predominant myoclonic jerks of upper limbs, often provoked by cognitive activities, and typically responsive to treatment with sodium valproate. Neurophysiological, neuropsychological and imaging studies in juvenile myoclonic epilepsy have consistently pointed towards subtle abnormalities in the medial frontal lobes. Using functional magnetic resonance imaging with an executive frontal lobe paradigm, we investigated cortical activation patterns and interaction between cortical regions in 30 patients with juvenile myoclonic epilepsy and 26 healthy controls. With increasing cognitive demand, patients showed increasing coactivation of the primary motor cortex and supplementary motor area. This effect was stronger in patients still suffering from seizures, and was not seen in healthy controls. Patients with juvenile myoclonic epilepsy showed increased functional connectivity between the motor system and frontoparietal cognitive networks. Furthermore, we found impaired deactivation of the default mode network during cognitive tasks with persistent activation in medial frontal and central regions in patients. Coactivation in the motor cortex and supplementary motor area with increasing cognitive load and increased functional coupling between the motor system and cognitive networks provide an explanation how cognitive effort can cause myoclonic jerks in juvenile myoclonic epilepsy. The supplementary motor area represents the anatomical link between these two functional systems, and our findings may be the functional correlate of previously described structural abnormalities in the medial frontal lobe in juvenile myoclonic epilepsy.

Mapping of a locus for a familial autosomal recessive idiopathic myoclonic epilepsy of infancy to chromosome 16p13.

PubMed Central

Zara, F; Gennaro, E; Stabile, M; Carbone, I; Malacarne, M; Majello, L; Santangelo, R; de Falco, F A; Bricarelli, F D

2000-01-01

Myoclonic epilepsies with onset in infancy and childhood are clinically and etiologically heterogeneous. Although genetic factors are thought to play an important role, to date very little is known about the etiology of these disorders. We ascertained a large Italian pedigree segregating a recessive idiopathic myoclonic epilepsy that starts in early infancy as myoclonic seizures, febrile convulsions, and tonic-clonic seizures. We typed 304 microsatellite markers spanning the 22 autosomes and mapped the locus on chromosome 16p13 by linkage analysis. A maximum LOD score of 4.48 was obtained for marker D16S3027 at recombination fraction 0. Haplotype analysis placed the critical region within a 3.4-cM interval between D16S3024 and D16S423. The present report constitutes the first example of an idiopathic epilepsy that is inherited as an autosomal recessive trait. PMID:10741954

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

PubMed

van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

2015-12-01

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

Senile myoclonic epilepsy in Down syndrome: a video and EEG presentation of two cases.

PubMed

De Simone, Roberto; Daquin, Géraldine; Genton, Pierre

2006-09-01

Myoclonic epilepsy is being increasingly recognized as a late-onset complication in middle-aged or elderly patients with Down syndrome, in association with cognitive decline. We show video and EEG recordings of two patients, both aged 56 years, diagnosed with this condition. At onset, myoclonic epilepsy in elderly DS patients may resemble, in its clinical expression, the classical juvenile myoclonic epilepsy with the characteristic occurrence of jerks on awakening. It is clearly associated with an Alzheimer-type dementia, and may also occur in non-DS patients with Alzheimer's disease: hence the possible denomination of "senile myoclonic epilepsy". [Published with video sequences].

Analysis of the tremor in juvenile myoclonic epilepsy.

PubMed

Aydin-Özemir, Zeynep; Matur, Zeliha; Baykan, Betul; Bilgic, Başar; Tekturk, Pınar; Bebek, Nerses; Gurses, Candan; Hanagasi, Hasmet; Oge, Ali Emre

2016-12-01

We aimed to investigate juvenile myoclonic epilepsy (JME) patients complaining of tremor unrelated to valproate (VPA) treatment and evaluate if there were differences between JME patients with and without tremor and essential tremor (ET) patients to exclude comorbidity. Fifteen JME cases with the complaint of tremor, 14 JME patients without tremor, 14 patients with ET and 14 healthy subjects (HS) were included. Regularity, frequency and amplitude of the tremor and superimposed myoclonia were assessed by accelerometric analysis. Cortical SEPs evoked by the stimulation of the median nerve were recorded bilaterally. Clinical and neurophysiologic features were statistically compared between the groups. Amplitude of postural tremor of the left hand was significantly increased in the ET group compared to JME patients with tremor, but there were no differences regarding to frequency. Strikingly, there were superimposed irregular, low-amplitude inconstant myoclonic jerks located to distal part of the fingers in JME group with tremor. Initial frequency of myoclonic seizures was also significantly higher in this group compared to JME patients without tremor but this difference disappeared after treatment. The group of JME with tremor had the highest N20-P25 and P25-N35 amplitudes, followed by JME without tremor, ET and HS, respectively. Tremulous hand movements in JME resembled ET, but their amplitude was lower and characterized with accompanying irregular myoclonic jerks. The presence of tremor in JME patients should be taken into consideration to create more homogeneous groups in genetic and pathophysiological studies of JME. Copyright © 2016 Elsevier B.V. All rights reserved.

Severe early-onset epileptic encephalopathy due to mutations in the KCNA2 gene: Expansion of the genotypic and phenotypic spectrum.

PubMed

Hundallah, Khaled; Alenizi, Asma'a; AlHashem, Amal; Tabarki, Brahim

2016-07-01

Recently, de novo loss- or gain-of-function mutations in the KCNA2 gene; have been described in individuals with epileptic encephalopathy, ataxia or intellectual disability. In this report, we describe a further case of KCNA2-early-onset epileptic encephalopathy. The patient presented since birth with intractable seizures, progressive microcephaly, developmental delay, and progressive brain atrophy. Whole-exome sequencing showed a novel de novo mutation in the KCNA2 gene: c.1120A > G (p.Thr374Ala). This case expands the genotypic and phenotypic disease spectrum of this genetic form of KCNA2-early onset epileptic encephalopathy. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

PubMed

Palmer, Samantha; Towne, Meghan C; Pearl, Phillip L; Pelletier, Renee C; Genetti, Casie A; Shi, Jiahai; Beggs, Alan H; Agrawal, Pankaj B; Brownstein, Catherine A

2016-11-01

Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

PubMed

Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

2012-05-01

Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Diagnostic and prognostic factors for acute encephalopathy.

PubMed

Motojima, Yukiko; Nagura, Michiaki; Asano, Yoshitaka; Arakawa, Hiroshi; Takada, Eiko; Sakurai, Yoshio; Moriwaki, Koichi; Tamura, Masanori

2016-11-01

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 (NH 3 ), 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.

Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

PubMed

Miyake, Noriko; Fukai, Ryoko; Ohba, Chihiro; Chihara, Takahiro; Miura, Masayuki; Shimizu, Hiroshi; Kakita, Akiyoshi; Imagawa, Eri; Shiina, Masaaki; Ogata, Kazuhiro; Okuno-Yuguchi, Jiu; Fueki, Noboru; Ogiso, Yoshifumi; Suzumura, Hiroshi; Watabe, Yoshiyuki; Imataka, George; Leong, Huey Yin; Fattal-Valevski, Aviva; Kramer, Uri; Miyatake, Satoko; Kato, Mitsuhiro; Okamoto, Nobuhiko; Sato, Yoshinori; Mitsuhashi, Satomi; Nishino, Ichizo; Kaneko, Naofumi; Nishiyama, Akira; Tamura, Tomohiko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Tanaka, Fumiaki; Saitsu, Hirotomo; Matsumoto, Naomichi

2016-10-06

We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

PubMed

Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

2014-06-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

Early Recognition of Chronic Traumatic Encephalopathy through FDDNP PET Imaging

DTIC Science & Technology

2014-10-01

Encephalopathy through FDDNP PET Imaging PRINCIPAL INVESTIGATOR: Charles Bernick, MD, MPH...Traumatic Encephalopathy through FDDNP PET Imaging 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0486 5c. PROGRAM ELEMENT NUMBER 6... Encephalopathy . This project will examine whether FDDNP PET imaging correlates with, and/or can predict, decline in cognitive function in those exposed to

[Pregnancy and labor associated with encephalopathy in neonates during the early neonatal period].

PubMed

Skrablin, S; Drazancić, A; Letica, N; Tadić, V

1992-01-01

Pregnancy complications, drugs and surgical interventions during pregnancy, fetal growth, medications and interventions during labor, labor complications as well as fetal heart activity during labor in a group of 114 term infants without malformations, but with signs of central nervous system (CNS) damage throughout early neonatal period are compared with paired group of term healthy infants born in the same presentation and mode of delivery. Among prelabor factors only maternal hypertension (found in 16.7% of encephalopathy children versus 0.8% in a control group) was significantly correlated with CNS damage. Fetal growth retardation and long term ritodrine administration were found more frequent in encephalopathy than in healthy group of infants, although statistical significance between the groups could not be demonstrated. A prolonged second stage of labor, high oxytocin dosage, too frequent uterine contractions and vacuum extractions were found significantly correlated with neonatal encephalopathy. CTG pattern during labor was normal in only 28.9% of children, with encepalopathy prepathologic in 46.4% and pathologic in 24.7%. The respective percentages for healthy newborns were: 82.5%, 16.25% and 1.2%. All differences between the groups were statistically significant. Mean duration of prepathologic CTG score in the group of infants with encephalopathy (78.8 minutes) as well as of pathologic score (51.7 minutes) was significantly longer than in healthy infants (23.7 minutes prepathologic and 7 minutes pathologic).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic Encephalopathy: Early Diagnosis in Pediatric Patients With Cirrhosis

PubMed Central

DARA, Naghi; SAYYARI, Ali-Akbar; IMANZADEH, Farid

2014-01-01

Objective As acute liver failure (ALF) and chronic liver disease (cirrhosis) continue to increase in prevalence, we will see more cases of hepatic encephalopathy. Primary care physician are often the first to suspect it, since they are familiar with the patient’s usual physical and mental status. This serious complication typically occurs in patients with severe comorbidities and needs multidisciplinary evaluation and care. Hepatic encephalopathy should be considered in any patient with acute liver failure and cirrhosis who presents with neuropsychiatric manifestations, decrease level of consciousness (coma), change of personality, intellectual and behavioral deterioration, speech and motor dysfunction. Every cirrhotic patient may be at risk; potential precipitating factors should be addressed in regular clinic visits. The encephalopathy of liver disease may be prominent, or can be present in subtle forms, such as decline of school performance, emotional outbursts, or depression. “Subtle form” of hepatic encephalopathy may not be obvious on clinical examination, but can be detected by neurophysiologic and neuropsychiatric testing. PMID:24665321

Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

PubMed

Radaelli, Graciane; de Souza Santos, Francisco; Borelli, Wyllians Vendramini; Pisani, Leonardo; Nunes, Magda Lahorgue; Scorza, Fulvio Alexandre; da Costa, Jaderson Costa

2018-06-12

Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe

Reliability of Early Magnetic Resonance Imaging (MRI) and Necessity of Repeating MRI in Noncooled and Cooled Infants With Neonatal Encephalopathy.

PubMed

Chakkarapani, Elavazhagan; Poskitt, Kenneth J; Miller, Steven P; Zwicker, Jill G; Xu, Qi; Wong, Darren S T; Roland, Elke H; Hill, Alan; Chau, Vann

2016-04-01

In cooled newborns with encephalopathy, although late magnetic resonance imaging (MRI) scan (10-14 days of age) is reliable in predicting long-term outcome, it is unknown whether early scan (3-6 days of life) is. We compared the predominant pattern and extent of lesion between early and late MRI in 89 term neonates with neonatal encephalopathy. Forty-three neonates (48%) were cooled. The predominant pattern of lesions and the extent of lesion in the watershed region agreed near perfectly in noncooled (kappa = 0.94; k = 0.88) and cooled (k = 0.89; k = 0.87) infants respectively. There was perfect agreement in the extent of lesion in the basal nuclei in noncooled infants (k = 0.83) and excellent agreement in cooled infants (k = 0.67). Changes in extent of lesions on late MRI occurred in 19 of 89 infants, with higher risk in infants with hypoglycemia and moderate-severe lesions in basal nuclei. In most term neonates with neonatal encephalopathy, early MRI (relative to late scan) robustly predicts the predominant pattern and extent of injury. © The Author(s) 2015.

Video/EEG aspects of early-infantile epileptic encephalopathy with suppression-bursts (Ohtahara syndrome).

PubMed

Fusco, L; Pachatz, C; Di Capua, M; Vigevano, F

2001-11-01

Early-infantile epileptic encephalopathy (EIEE) with suppression-bursts is a severe neonatal epileptic encephalopathy. The etiology is multiple, with cerebral malformations as the more frequent. We review the clinical and video/EEG aspects of eight infants with EIEE. These infants, aged between 4 and 70 days at the time of video/EEG recordings, were studied in relation to their clinical and video/EEG characteristics, evolution, persistence of suppression-burst pattern and etiology. Seven of the eight infants showed an ictal clinical sign correlated to the burst of the suppression-burst pattern, four of whom died within 11 months of age. The other three are alive. One, now aged 4 years, underwent surgery for hemimegalencephaly and is seizure-free, with good neurological outcome. One, now aged 9 months, was pyridoxine-dependent and she is seizure-free, and with normal neurological evolution under pyridoxine therapy. One, now aged 3 years and 9 months, is seizure-free, but with severe neurological and cognitive impairment. The only child who did not show a clinical ictal correlation of burst is also alive, now aged 3 years and 9 months, with drug-resistant epilepsy, and severe neurological and cognitive deficits. With regard to the etiology, three showed structural abnormalities, two more showed some signs of prenatal origin of neurological disease, and three had metabolic etiology. Our study confirms that EIEE is a severe age-dependent early epileptic encephalopathy. The etiology is mostly malformative. The prognosis is poor regarding motor and cognitive development, seizures, as well as life expectancies. The presence of an ictal burst of the suppression-burst pattern usually correlates with a negative outcome.

Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

PubMed Central

2011-01-01

Background To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg/dL (2.6 mmol/L)] and hyperglycaemia [> 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome. PMID:21294901

Need for early diagnosis of mental and mobility changes in Wernicke encephalopathy.

PubMed

Wijnia, Jan W; Oudman, Erik; Bresser, Esmay L; Gerridzen, Ineke J; van de Wiel, Albert; Beuman, Carla; Mulder, Cornelis L

2014-12-01

Korsakoff syndrome is a chronic form of amnesia resulting from thiamine deficiency. The syndrome can develop from unrecognized or undertreated Wernicke encephalopathy. The intra-individual course of Wernicke-Korsakoff syndrome has not been studied extensively, nor has the temporal progression of gait disturbances and other symptoms of Wernicke encephalopathy. Here we present the detailed history of a patient whose acute symptoms of Wernicke encephalopathy were far from stable. We follow his mobility changes and the shifts in his mental status from global confusion and impaired consciousness to more selective cognitive deficits. His Wernicke encephalopathy was missed and left untreated, being labeled as "probable" Korsakoff syndrome. Patients with a history of self-neglect and alcohol abuse, at risk of or suffering with Wernicke encephalopathy, should receive immediate and adequate vitamin replacement. Self-neglecting alcoholics who are bedridden may have severe illness and probably active Wernicke encephalopathy. In these patients, mobility changes, delirium, or impaired consciousness can be an expression of Wernicke encephalopathy, and should be treated to prevent further damage from the neurologic complications of thiamine deficiency.

Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy.

PubMed

Lally, Peter J; Montaldo, Paolo; Oliveira, Vânia; Swamy, Ravi Shankar; Soe, Aung; Shankaran, Seetha; Thayyil, Sudhin

2018-07-01

We examined the brain injury and neurodevelopmental outcomes in a prospective cohort of 10 babies with mild encephalopathy who had early cessation of cooling therapy. All babies had MRI and spectroscopy within 2 weeks after birth and neurodevelopmental assessment at 2 years. Cooling was prematurely discontinued at a median age of 9 hours (IQR 5-13) due to rapid clinical improvement. Five (50%) had injury on MRI or spectroscopy, and two (20%) had an abnormal neurodevelopmental outcome at 2 years. Premature cessation of cooling therapy in babies with mild neonatal encephalopathy does not exclude residual brain injury and adverse long-term neurodevelopmental outcomes. This study refers to babies recruited into the MARBLE study (NCT01309711, pre-results stage). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene.

PubMed

Bahi-Buisson, Nadia; Girard, Benoit; Gautier, Agnes; Nectoux, Juliette; Fichou, Yann; Saillour, Yoann; Poirier, Karine; Chelly, Jamel; Bienvenu, Thierry

2010-01-05

We report a 2-year-old girl with early onset seizures variant of Rett syndrome with a deletion at Xp22 detected by multiplex ligation-dependent probe amplification (MLPA) technique. This patient presented with tonic seizures at 7 days of life. Subsequently, she developed infantile spasms at three months and finally refractory myoclonic epilepsy. She demonstrated severe encephalopathy with hypotonia, deceleration of head growth, with eye gaze but limited eye pursuit, no language, limited hand use, and intermittent hand stereotypies. This combination of clinical features, suggestive of early onset variant of Rett syndrome led us to screen the CDKL5 gene. In a first step, screening of the whole coding sequence of the CDKL5 gene revealed no point mutations. In a second step, we searched gross rearrangements by MLPA and identified a microdeletion affecting both the promoter and exon 1 in CDKL5. Subsequent analysis on a Nimblegen HD2 microarray confirmed a deletion of approximately 300 kb at Xp22, including the BEND2, SCML2, and CDKL5 genes. In conclusion, our report suggests that searching for large rearrangements in CDKL5 should be considered in girls with early onset seizures and Rett-like features. (c) 2009 Wiley-Liss, Inc.

Myoclonic epilepsy in Down syndrome and Alzheimer disease.

PubMed

Aller-Alvarez, J S; Menéndez-González, M; Ribacoba-Montero, R; Salvado, M; Vega, V; Suárez-Moro, R; Sueiras, M; Toledo, M; Salas-Puig, J; Álvarez-Sabin, J

2017-03-01

Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges. We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

PubMed

Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

2009-11-01

Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

CDKL5 variant in a boy with infantile epileptic encephalopathy: case report.

PubMed

Wong, Virginia Chun-Nei; Kwong, Anna Ka-Yee

2015-04-01

A Chinese boy presented at 18 months with intractable epilepsy, developmental delay and autistic features. He had multiple seizure types, including absence, myoclonic seizures, limb spasm and tonic seizures. His seizures were finally controlled at 3 years of age with clonazepam and a short course of chloral hydrate incidentally given for his insomnia. Subsequently, he had improvement in his communication skills. A novel hemizygous missense variant (c.1649G>A; p.R550Q) in exon 12 of CDKL5 gene was detected for him, his asymptomatic mother and elder sister. His phenotype is less severe than other male cases. We recommend screening CDKL5 for boys with pharmarco-resistant epilepsy and a trial of benzodiazepines for Infantile Epileptic Encephalopathy (IEE). Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?

PubMed Central

Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

2014-01-01

Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy. PMID:25001494

Early progressive encephalopathy in boys and MECP2 mutations.

PubMed

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

2006-07-11

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.

The phenotypic spectrum of SCN8A encephalopathy

PubMed Central

Larsen, Jan; Carvill, Gemma L.; Gardella, Elena; Kluger, Gerhard; Schmiedel, Gudrun; Barisic, Nina; Depienne, Christel; Brilstra, Eva; Mang, Yuan; Nielsen, Jens Erik Klint; Kirkpatrick, Martin; Goudie, David; Goldman, Rebecca; Jähn, Johanna A.; Jepsen, Birgit; Gill, Deepak; Döcker, Miriam; Biskup, Saskia; McMahon, Jacinta M.; Koeleman, Bobby; Harris, Mandy; Braun, Kees; de Kovel, Carolien G.F.; Marini, Carla; Specchio, Nicola; Djémié, Tania; Weckhuysen, Sarah; Tommerup, Niels; Troncoso, Monica; Troncoso, Ledia; Bevot, Andrea; Wolff, Markus; Hjalgrim, Helle; Guerrini, Renzo; Møller, Rikke S.

2015-01-01

Objective: SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. Methods: We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. Results: Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. Conclusion: SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent. PMID:25568300

The phenotypic spectrum of SCN8A encephalopathy.

PubMed

Larsen, Jan; Carvill, Gemma L; Gardella, Elena; Kluger, Gerhard; Schmiedel, Gudrun; Barisic, Nina; Depienne, Christel; Brilstra, Eva; Mang, Yuan; Nielsen, Jens Erik Klint; Kirkpatrick, Martin; Goudie, David; Goldman, Rebecca; Jähn, Johanna A; Jepsen, Birgit; Gill, Deepak; Döcker, Miriam; Biskup, Saskia; McMahon, Jacinta M; Koeleman, Bobby; Harris, Mandy; Braun, Kees; de Kovel, Carolien G F; Marini, Carla; Specchio, Nicola; Djémié, Tania; Weckhuysen, Sarah; Tommerup, Niels; Troncoso, Monica; Troncoso, Ledia; Bevot, Andrea; Wolff, Markus; Hjalgrim, Helle; Guerrini, Renzo; Scheffer, Ingrid E; Mefford, Heather C; Møller, Rikke S

2015-02-03

SCN8A encodes the sodium channel voltage-gated α8-subunit (Nav1.6). SCN8A mutations have recently been associated with epilepsy and neurodevelopmental disorders. We aimed to delineate the phenotype associated with SCN8A mutations. We used high-throughput sequence analysis of the SCN8A gene in 683 patients with a range of epileptic encephalopathies. In addition, we ascertained cases with SCN8A mutations from other centers. A detailed clinical history was obtained together with a review of EEG and imaging data. Seventeen patients with de novo heterozygous mutations of SCN8A were studied. Seizure onset occurred at a mean age of 5 months (range: 1 day to 18 months); in general, seizures were not triggered by fever. Fifteen of 17 patients had multiple seizure types including focal, tonic, clonic, myoclonic and absence seizures, and epileptic spasms; seizures were refractory to antiepileptic therapy. Development was normal in 12 patients and slowed after seizure onset, often with regression; 5 patients had delayed development from birth. All patients developed intellectual disability, ranging from mild to severe. Motor manifestations were prominent including hypotonia, dystonia, hyperreflexia, and ataxia. EEG findings comprised moderate to severe background slowing with focal or multifocal epileptiform discharges. SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases. Outcome is often poor and includes hypotonia and movement disorders. The majority of mutations arise de novo, although we observed a single case of somatic mosaicism in an unaffected parent. © 2015 American Academy of Neurology.

Paroxysmal myoclonic dystonia with vocalisations: new entity or variant of preexisting syndromes?

PubMed Central

Feinberg, T E; Shapiro, A K; Shapiro, E

1986-01-01

From among 1377 patients with movement disorders, four patients had an unusual movement disorder characterised by paroxysmal bursts of involuntary, regular, repetitive, rhythmic, bilateral, coordinated, simultaneous, stereotypic myoclonus and vocalisations, often associated with tonic symptoms, interference with voluntary functioning, presence of hyperactivity, attention and learning disabilities, and resistance to treatment with haloperidol and other drugs. This symptom complex may represent a new disease entity, referred to here as paroxysmal myoclonic dystonia with vocalisations or a variant or combination of other movement disorders such as Gilles de la Tourette, myoclonic, or dystonic syndromes. PMID:3457101

Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.

PubMed

Depienne, Christel; Bouteiller, Delphine; Keren, Boris; Cheuret, Emmanuel; Poirier, Karine; Trouillard, Oriane; Benyahia, Baya; Quelin, Chloé; Carpentier, Wassila; Julia, Sophie; Afenjar, Alexandra; Gautier, Agnès; Rivier, François; Meyer, Sophie; Berquin, Patrick; Hélias, Marie; Py, Isabelle; Rivera, Serge; Bahi-Buisson, Nadia; Gourfinkel-An, Isabelle; Cazeneuve, Cécile; Ruberg, Merle; Brice, Alexis; Nabbout, Rima; Leguern, Eric

2009-02-01

Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.

Not all SCN1A epileptic encephalopathies are Dravet syndrome: Early profound Thr226Met phenotype.

PubMed

Sadleir, Lynette G; Mountier, Emily I; Gill, Deepak; Davis, Suzanne; Joshi, Charuta; DeVile, Catherine; Kurian, Manju A; Mandelstam, Simone; Wirrell, Elaine; Nickels, Katherine C; Murali, Hema R; Carvill, Gemma; Myers, Candace T; Mefford, Heather C; Scheffer, Ingrid E

2017-09-05

To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder. A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation. We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable. Here, we present a phenotype-genotype correlation for SCN1A . We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Epilepsy with myoclonic-atonic seizures (Doose syndrome): When video-EEG polygraphy holds the key to syndrome diagnosis.

PubMed

Dragoumi, Pinelopi; Chivers, Fiona; Brady, Megan; Craft, Sheila; Mushati, David; Venkatachalam, Gopalakrishnan; Cross, Judith Helen; Das, Krishna B

2016-01-01

An electroclinical epilepsy syndrome diagnosis enables physicians to predict outcomes as well as select appropriate treatment options. We report a child who presented with reflex myoclonus at the age of 9 months and was initially diagnosed with myoclonic epilepsy in infancy. After 9 years of medically resistant myoclonic seizures, extensive investigations, and emerging learning difficulties, she was referred for video-telemetry to characterize her seizures in an attempt to make a syndromic diagnosis. A three-day video-telemetry assessment was performed to document seizures. Neck and deltoid EMG channels were applied from the onset of the recording. Frequent generalized bursts of 3- to 5-Hz spike/polyspike and slow wave discharges, associated with clinical manifestations, mostly myoclonic seizures, were noted. In addition, definite atonic components were noted on the neck EMG as well as the deltoids associated with the slow component of the ictal discharges. The EEG and polygraphy findings are suggestive of a generalized epilepsy characterized by predominantly myoclonic seizures with atonic components. This raises the possibility whether a variant of epilepsy with myoclonic-atonic seizures (Doose syndrome) may be the underlying diagnosis for this girl. A trial of the ketogenic diet would therefore be considered as an option in her future management in view of its beneficial effect in this condition.

Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

PubMed

Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

2016-01-01

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

Chronic traumatic encephalopathy: The unknown disease.

PubMed

Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

2017-04-01

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.

Toxic Encephalopathy

PubMed Central

Kim, Jae Woo

2012-01-01

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

Encephalopathy and liver transplantation.

PubMed

Chavarria, Laia; Cordoba, Juan

2013-06-01

Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy.

PubMed

Cichoż-Lach, Halina; Michalak, Agata

2013-01-07

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.

Wernicke encephalopathy in a patient with liver failure

PubMed Central

Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

2016-01-01

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

Atypical subacute sclerosing panencephalitis with short onset latency.

PubMed

Saurabh, Kumar; Gupta, Ratan; Khare, Shashi; Sharma, Shobha

2013-02-01

An 11-month-old boy presented with focal seizures, myoclonic jerks and altered sensorium of one month duration, with a history of measles at eight months of age. A diagnosis of Subacute sclerosing panencephalitis (SSPE) was made on the basis of typical EEG changes and presence of anti-measles antibody in cerebrospinal fluid. A differential diagnosis of SSPE should be considered in all forms of acute encephalopathy in infants for early diagnosis and management.

[Follow-up of newborns with hypoxic-ischaemic encephalopathy].

PubMed

Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

2014-07-01

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.

Hyperemesis gravidarum complicated by Wernicke's encephalopathy.

PubMed

Spruill, Steven C; Kuller, Jeffrey A

2002-05-01

Wernicke's encephalopathy is usually associated with alcohol abuse, but can also occur with hyperemesis gravidarum. The effect of delay in thiamine replacement on fetal outcomes is unknown. We present a case of this complication. A primipara with hyperemesis was admitted for mental status changes in her 14th week of pregnancy. Physical examination revealed a lethargic patient with ophthalmoplegia, ataxia, and hyporeflexia. Parenteral thiamine therapy was started. The patient improved rapidly although the ataxia persisted. A spontaneous abortion occurred 2 weeks later. Wernicke's encephalopathy can complicate hyperemesis gravidarum. Early thiamine replacement may decrease the chances of spontaneous abortion.

Interictal mood and personality disorders in temporal lobe epilepsy and juvenile myoclonic epilepsy.

PubMed Central

Perini, G I; Tosin, C; Carraro, C; Bernasconi, G; Canevini, M P; Canger, R; Pellegrini, A; Testa, G

1996-01-01

BACKGROUND: Mood disorders have been described as the commonest psychiatric disorders in patients with temporal lobe epilepsy. Secondary depression in temporal lobe epilepsy could be interpreted either as an adjustment reaction to a chronic disease or as a limbic dysfunction. To clarify this issue, a controlled study of psychiatric disorders was conducted in different forms of epileptic and non-epileptic chronic conditions. METHODS: Twenty outpatients with temporal lobe epilepsy, 18 outpatients with juvenile myoclonic epilepsy--a primary generalised seizure disorder--20 matched type I diabetic patients, and 20 matched normal controls were assessed by a structured interview (SADS) and by self rating scales (Beck depression inventory (BDI) and the state and trait anxiety scales STAIX1 and STAIX2). RESULTS: Sixteen (80%) patients with temporal lobe epilepsy fulfilled the criteria for a psychiatric diagnosis at the SADS interview with a significantly higher frequency than patients with juvenile myoclonic epilepsy (22%) and diabetic patients (10%) (P < 0.0001). The most frequent disorder in temporal lobe epilepsy was a mood disorder: 11 (55%) patients with temporal lobe epilepsy had depression compared with three patients with juvenile myoclonic epilepsy and two diabetic patients (P < 0.001). Eight patients with temporal lobe epilepsy with an affective disorder also had a comorbid personality or anxiety disorder. Patients with temporal lobe epilepsy scored significantly higher on BDI, STAIX1, and STAIX2 than the three control groups (P < 0.001, P < 0.01, P < 0.001). CONCLUSIONS: Patients with temporal lobe epilepsy have a higher incidence of affective and personality disorders, often in comorbidity, than patients with juvenile myoclonic epilepsy and diabetic patients suggesting that these psychiatric disorders are not an adjustment reaction to a chronic disease but rather reflect a limbic dysfunction. PMID:8971108

Electroencephalographic features of benign adult familial myoclonic epilepsy.

PubMed

Toyota, Tomoko; Akamatsu, Naoki; Tanaka, Akihiro; Tsuji, Sadatoshi; Uozumi, Takenori

2014-02-01

To investigate electroencephalographic (EEG) features of benign adult familial myoclonic epilepsy (BAFME). We reviewed interictal EEG features in patients with BAFME treated between April 2005 and November 2012 at a tertiary referral center. The diagnostic criteria for BAFME were the presence of infrequent generalized tonic-clonic seizures, myoclonus or myoclonic seizures, and autosomal dominant inheritance. Interictal EEG findings of epilepsy with generalized tonic-clonic seizure only (EGTCS) were reviewed for comparison. We randomly selected 10 generalized spike/polyspike and wave complexes (GSW) for each BAFME patient and measured the duration of them. Photic stimulation and hyperventilation were performed in all. Nineteen (eight men, 11 women) patients with BAFME were included in this study. The mean frequency of GSW was 4.3±1.0Hz (mean±SD, n=14) in BAFME and 3.2±0.8Hz (n=10) in EGTCS. There was a statistically significant difference (p=0.008) between the two. Photoparoxysmal responses (PPR) were noted in 18 (95%) patients with BAFME but 1 (10%) with EGTCS. Faster frequency of GSW, compared with that in EGTCS, accompanied by PPR may be characteristic EEG features of BAFME. These findings may lead the diagnosis of BAFME. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

[Efficiency of mexidol during perinatal encephalopathy in early age children].

PubMed

Natriashvili, G D; Kapanadze, N B; Natriashvili, S G

2005-06-01

We have investigated 200 patients 0-4 months of age (boys 110 and girls - 90), 120 of them under 1 month of age and 80 children from 1 to 4 months. The evaluation of the neurologic status of patients was performed 40-60 minutes after feeding in a relaxed condition. From the additional methods of the investigation of the nervous system, the most informative was the neurosonoscopy. We have divided patients into two groups according to the clinical syndromes: I gr. neuro-reflexion irritation syndrome (118 patients), II gr.--depression syndrome (82 patients). According to the treatment regimen patients also have been divided into two groups: the basic group (104 patients) with treatment only by mexydol (mexydol in a dose of 5 mg/kg and 0,3 ml in the form of injections twice a day. Injections were initiated at the acute stage of the disease) and the control group (96 patients) with no treatment. Efficiency of mexidol was estimated comparison of the findings in the basic and control groups based both on a clinical status and on the neurosonoscopic findings. Positive dynamics was observed in patients of the basic group. Verification of mexydol efficiency was performed by neurosonoscopic investigations. In a small portion of patients positive dynamics was not observed. These patients were from the age group from 3 to 4 months, which confirms that earlier and optimal treatment contribute to the prevention of severe neurological outcomes. It may be concluded that: 1. Mexydol acting on the pathogenetic mechanisms of perinatal encephalopathy, reduces reflexion irritation and depression syndromes both in neonatal and early age children. 2. Mexydol induces normalization of pathological neurosonoscopic patterns. 3. Mexydol with its wide pharmacological spectrum of action is an effective medicine in treatment of perinatal encephalopathy.

[Therapeutic effect of early applying hydrotherapy with Chinese drugs on children hypoxic ischemic encephalopathy].

PubMed

Ma, Yun-Zhi; Zhai, Hong-Yin; Su, Chun-Ya

2009-02-01

To observe the therapeutic effect of hydrotherapy with Chinese drugs (HT-C) in early intervention on children hypoxic ischemic encephalopathy (HIE). HIE children were assigned to the treatment group and the control group, 50 in each, at random depending on the willingness of patients' parents. Both groups received the conventional functional training, according to the "0 -3-year-old early intervention outline", but for the treatment group, HT-C was applied additionally. Indexes for quality of sleep, gross motor function, severity of spasm and intellectual development were observed and compared before and after treatment to assess the therapeutic effects. Therapeutic effect in the treatment group was better than that in the control group in all the indexes observed, showing statistical significance (all P <0.05). Early intervention of HT-C could improve clinical symptom, promote the functional recovery and intellectual development in children HIE, and also could reduce or prevent the sequelae occurrence of the nervous system in them.

Late-onset Leigh syndrome with myoclonic epilepsy with ragged-red fibers.

PubMed

Monden, Yukifumi; Mori, Masato; Kuwajima, Mari; Goto, Tamako; Yamagata, Takanori; Momoi, Mariko Y

2013-06-01

We report the case of a boy with myoclonic epilepsy with ragged-red fibers (MERRF) who had astatic seizures since 2 years of age and later developed ataxia, absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed late-onset Leigh syndrome (LS) when he contracted pneumonia at 6 years. He developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem, basal ganglia, and cerebral cortex. Three similar cases have been reported; two carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype of MERRF in the early stage and late-onset Leigh syndrome in the late course of the disease. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

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

2015-08-01

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

Unconsciousness, automatisms, and myoclonic jerks with diffuse rhythmic 9-Hz discharges.

PubMed

Nadel, A; Waddell, G; Volow, M; Escueta, A V

1975-09-01

A 25-year-old man presented with seizures characterized by unconsciousness, automatic behavior, and myoclonic jerks lasting 0.5 to 8 sec. Videotape analysis of 300 simultaneously recorded electroencephalographic and clinical attacks revealed 8- to 9-Hz 150 to 200 muV sharp waves beginning in both medial temporal areas during eyelid flutters. When discharges spread diffusely on both sides and lasted 2 to 3 sec, 20 degrees forward flexion of the head, unconsciousness, pupil dilation, and staring became evident. Asymmetrical myoclonic jerks invariably appeared. When paroxysms were greater than 3 sec, automatisms and tonic posturing occurred. The electroencephalographic and clinical seizures appeared during the awake and relaxed states, i.e., with normal alpha rhythm. They were suppressed during physical and mental activities and during sleep, i.e., in the absence of alpha rhythm. Our studies suggest that these seizures associated with diffuse electroencephalographic alpha-like activities are subcortical in origin and should be tested in their responsivity to alpha suppressants and inducers.

A novel mutation in STXBP1 gene in a child with epileptic encephalopathy and an atypical electroclinical pattern.

PubMed

Romaniello, Romina; Zucca, Claudio; Tenderini, Erika; Arrigoni, Filippo; Ragona, Francesca; Zorzi, Giovanna; Bassi, Maria Teresa; Borgatti, Renato

2014-02-01

Mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies. A 3-year-old boy affected by epileptic encephalopathy started at 8 months of age is described. Focal epilepsy was characterized by drug resistance seizures with multifocal interictal and ictal electroencephalographic (EEG) features and variable EEG focus. Direct sequencing of the STXBP1 gene showed a novel de novo mutation (c.751G>A), leading to a p.Ala251Thr substitution. Based on reported data, treatment with vigabatrin was attempted and patient became immediately seizure free for 4 months. The present case further expands the clinical spectrum of "STXBP1-related encephalopathy" suggesting molecular analysis of STXBP1 in early onset epileptic encephalopathies of unknown etiology (with onset within the first year of life). In addition, the case provides valuable suggestions on seizures treatment in STXBP1 mutated subjects.

A new infectious encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX).

PubMed

Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Yasukawa, Kumi; Takanashi, Jun-Ichi

2017-09-15

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.

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

PubMed Central

Wielaender, Franziska; Sarviaho, Riika; James, Fiona; Hytönen, Marjo K.; Cortez, Miguel A.; Kluger, Gerhard; Koskinen, Lotta L. E.; Arumilli, Meharji; Kornberg, Marion; Bathen-Noethen, Andrea; Tipold, Andrea; Rentmeister, Kai; Bhatti, Sofie F. M.; Hülsmeyer, Velia; Boettcher, Irene C.; Tästensen, Carina; Flegel, Thomas; Leeb, Tosso; Matiasek, Kaspar; Fischer, Andrea; Lohi, Hannes

2017-01-01

The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization. PMID:28223533

Juvenile myoclonic epilepsy and narcolepsy: A series of three cases.

PubMed

Joshi, Puja Aggarwal; Poduri, Annapurna; Kothare, Sanjeev V

2015-10-01

This paper sets out to demonstrate the coexistence of juvenile myoclonic epilepsy (JME) and narcolepsy that raises the possibility of a shared genetic predisposition to both conditions. The electronic medical records (EMRs) were searched for narcolepsy and JME over 10years. We identified three young adult women diagnosed with JME in their teenage years, with myoclonic, generalized tonic-clonic, and absence seizure semiologies, along with psychiatric comorbidity, well managed on lamotrigine and/or levetiracetam. Our patients were also found to have disturbed sleep preceding the diagnosis of JME by many years, including excessive daytime sleepiness (EDS), fragmented nocturnal sleep, hypnagogic vivid hallucinations, and REM behavior disorder along with daytime cataplexy. They were ultimately diagnosed with coexisting narcolepsy, confirmed by sleep studies and multiple sleep latency testing, along with positive genetic testing for HLA-DQB1*0602 in all three patients. Stimulants, selective serotonin receptor inhibitors, and/or sodium oxybate were used to successfully treat their narcolepsy. The coexistence of JME and narcolepsy has not been well recognized and may be clinically relevant. In addition, it raises the possibility of a shared genetic predisposition to both conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Hepatic Encephalopathy

MedlinePlus Videos and Cool Tools

... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

Hyperconnectivity in juvenile myoclonic epilepsy: a network analysis.

PubMed

Caeyenberghs, K; Powell, H W R; Thomas, R H; Brindley, L; Church, C; Evans, J; Muthukumaraswamy, S D; Jones, D K; Hamandi, K

2015-01-01

Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas. Using diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients. Neuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance. Our findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients.

Wernicke encephalopathy in a patient with liver failure: Clinical case report.

PubMed

Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

2016-07-01

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.

Early-onset encephalopathy with paroxysmal movement disorders and epileptic seizures without hemiplegic attacks: About three children with novel ATP1A3 mutations.

PubMed

Marzin, Pauline; Mignot, Cyril; Dorison, Nathalie; Dufour, Louis; Ville, Dorothée; Kaminska, Anna; Panagiotakaki, Eleni; Dienpendaele, Anne-Sophie; Penniello, Marie-José; Nougues, Marie-Christine; Keren, Boris; Depienne, Christel; Nava, Caroline; Milh, Mathieu; Villard, Laurent; Richelme, Christian; Rivier, Clotilde; Whalen, Sandra; Heron, Delphine; Lesca, Gaëtan; Doummar, Diane

2018-05-31

Heterozygous mutations in the ATP1A3 gene are responsible for various neurological disorders, ranging from early-onset alternating hemiplegia of childhood to adult-onset dystonia-parkinsonism. Next generation sequencing allowed the description of other phenotypes, including early-onset epileptic encephalopathy in two patients. We report on three more patients carrying ATP1A3 mutations with a close phenotype and discuss the relationship of this phenotype to alternating hemiplegia of childhood. The patients' DNA underwent next generation sequencing. A retrospective analysis of clinical case records is reported. Each of the three patients had an unreported heterozygous de novo sequence variant in ATP1A3. These patients shared a similar phenotype characterized by early-onset attacks of movement disorders, some of which proved to be epileptic, and severe developmental delay. (Hemi)plegic attacks had not been considered before genetic testing. Together with the two previously reported cases, our patients confirm that ATP1A3 mutations are associated with a phenotype combining features of early-onset encephalopathy, epilepsy and dystonic fits, as in the most severe forms of alternating hemiplegia of childhood, but in which (hemi)plegic attacks are absent or only suspected retrospectively. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.

PubMed

Ahearne, C E; Denihan, N M; Walsh, B H; Reinke, S N; Kenny, L C; Boylan, G B; Broadhurst, D I; Murray, D M

2016-01-01

A 1H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ2 = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score. © 2016 S. Karger AG, Basel.

Pathogenesis of Hepatic Encephalopathy

PubMed Central

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

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

Hyperconnectivity in juvenile myoclonic epilepsy: A network analysis

PubMed Central

Caeyenberghs, K.; Powell, H.W.R.; Thomas, R.H.; Brindley, L.; Church, C.; Evans, J.; Muthukumaraswamy, S.D.; Jones, D.K.; Hamandi, K.

2014-01-01

Objective Juvenile myoclonic epilepsy (JME) is a common idiopathic (genetic) generalized epilepsy (IGE) syndrome characterized by impairments in executive and cognitive control, affecting independent living and psychosocial functioning. There is a growing consensus that JME is associated with abnormal function of diffuse brain networks, typically affecting frontal and fronto-thalamic areas. Methods Using diffusion MRI and a graph theoretical analysis, we examined bivariate (network-based statistic) and multivariate (global and local) properties of structural brain networks in patients with JME (N = 34) and matched controls. Neuropsychological assessment was performed in a subgroup of 14 patients. Results Neuropsychometry revealed impaired visual memory and naming in JME patients despite a normal full scale IQ (mean = 98.6). Both JME patients and controls exhibited a small world topology in their white matter networks, with no significant differences in the global multivariate network properties between the groups. The network-based statistic approach identified one subnetwork of hyperconnectivity in the JME group, involving primary motor, parietal and subcortical regions. Finally, there was a significant positive correlation in structural connectivity with cognitive task performance. Conclusions Our findings suggest that structural changes in JME patients are distributed at a network level, beyond the frontal lobes. The identified subnetwork includes key structures in spike wave generation, along with primary motor areas, which may contribute to myoclonic jerks. We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients. PMID:25610771

ERP evidence of preserved early memory function in term infants with neonatal encephalopathy following therapeutic hypothermia.

PubMed

Pfister, Katie M; Zhang, Lei; Miller, Neely C; Hultgren, Solveig; Boys, Chris J; Georgieff, Michael K

2016-12-01

Neonatal encephalopathy (NE) carries high risk for neurodevelopmental impairments. Therapeutic hypothermia (TH) reduces this risk, particularly for moderate encephalopathy (ME). Nevertheless, these infants often have subtle functional deficits, including abnormal memory function. Detection of deficits at the earliest possible time-point would allow for intervention during a period of maximal brain plasticity. Recognition memory function in 22 infants with NE treated with TH was compared to 23 healthy controls using event-related potentials (ERPs) at 2 wk of age. ERPs were recorded to mother's voice alternating with a stranger's voice to assess attentional responses (P2), novelty detection (slow wave), and discrimination between familiar and novel (difference wave). Development was tested at 12 mo using the Bayley Scales of Infant Development, Third Edition (BSID-III). The NE group showed similar ERP components and BSID-III scores to controls. However, infants with NE showed discrimination at midline leads (P = 0.01), whereas controls showed discrimination in the left hemisphere (P = 0.05). Normal MRI (P = 0.05) and seizure-free electroencephalogram (EEG) (P = 0.04) correlated positively with outcomes. Infants with NE have preserved recognition memory function after TH. The spatially different recognition memory processing after early brain injury may represent compensatory changes in the brain circuitry and reflect a benefit of TH.

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

PubMed Central

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

2010-01-01

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

Progressive myoclonic epilepsies

PubMed Central

Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico

2014-01-01

Objective: To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. Methods: We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. Results: We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Conclusions: Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized. PMID:24384641

Treatment of Hyponatremic Encephalopathy in the Critically Ill.

PubMed

Achinger, Steven G; Ayus, Juan Carlos

2017-10-01

Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder. Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness. Hyponatremic encephalopathy is a frequently encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy and early treatment with hypertonic saline are critical for successful outcomes. Manifestations are varied, depending on the extent of CNS's adaptation to the hypoosmolar state. The absolute change in serum sodium alone is a poor predictor of clinical symptoms. However, certain patient specific risks factors are predictive of a poor outcome and are important to identify. Gender (premenopausal and postmenopausal females), age (prepubertal children), and the presence of hypoxia are the three main clinical risk factors and are more predictive of poor outcomes than the rate of development of hyponatremia or the absolute decrease in the serum sodium. In patients with hyponatremic encephalopathy exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over 10 minutes, should be promptly administered. The goal of this initial bolus is to quickly treat cerebral edema. If signs persist, the bolus should be repeated in order to achieve clinical remission. However, the total change in serum sodium should not exceed 5 mEq/L in the initial 1-2 hours and 15-20 mEq/L in the first 48 hours of treatment. It has recently been demonstrated in a prospective fashion that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given safely. It is critical to recognize the early signs of cerebral edema (nausea, vomiting, and headache

Current management of the infant who presents with neonatal encephalopathy.

PubMed

Wachtel, Elena V; Hendricks-Muñoz, Karen D

2011-01-01

Neonatal encephalopathy after perinatal hypoxic-ischemic insult is a major contributor to global child mortality and morbidity. Brain injury in term infants in response to hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy as well as predict their outcome. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Therapeutic hypothermia is the most promising neuroprotective intervention to date for infants with moderate to severe neonatal encephalopathy after perinatal asphyxia and has currently been incorporated in many neonatal intensive care units in developed countries. However, only 1 in 6 babies with encephalopathy will benefit from hypothermia therapy; many infants still develop significant adverse outcomes. To enhance the outcome, specific diagnostic predictors are needed to identify patients likely to benefit from hypothermia treatment. Studies are needed to determine the efficacy of combined therapeutic strategies with hypothermia therapy to achieve maximal neuroprotective effect. This review focuses on important concepts in the pathophysiology, diagnosis, and management of infants with neonatal encephalopathy due to perinatal asphyxia, including an overview of recently introduced novel therapies. © 2011 Published by Mosby, Inc.

TBC1D24 genotype–phenotype correlation

PubMed Central

Balestrini, Simona; Milh, Mathieu; Castiglioni, Claudia; Lüthy, Kevin; Finelli, Mattea J.; Verstreken, Patrik; Cardon, Aaron; Stražišar, Barbara Gnidovec; Holder, J. Lloyd; Lesca, Gaetan; Mancardi, Maria M.; Poulat, Anne L.; Repetto, Gabriela M.; Banka, Siddharth; Bilo, Leonilda; Birkeland, Laura E.; Bosch, Friedrich; Brockmann, Knut; Cross, J. Helen; Doummar, Diane; Félix, Temis M.; Giuliano, Fabienne; Hori, Mutsuki; Hüning, Irina; Kayserili, Hulia; Kini, Usha; Lees, Melissa M.; Meenakshi, Girish; Mewasingh, Leena; Pagnamenta, Alistair T.; Peluso, Silvio; Mey, Antje; Rice, Gregory M.; Rosenfeld, Jill A.; Taylor, Jenny C.; Troester, Matthew M.; Stanley, Christine M.; Ville, Dorothee; Walkiewicz, Magdalena; Falace, Antonio; Fassio, Anna; Lemke, Johannes R.; Biskup, Saskia; Tardif, Jessica; Ajeawung, Norbert F.; Tolun, Aslihan; Corbett, Mark; Gecz, Jozef; Afawi, Zaid; Howell, Katherine B.; Oliver, Karen L.; Berkovic, Samuel F.; Scheffer, Ingrid E.; de Falco, Fabrizio A.; Oliver, Peter L.; Striano, Pasquale; Zara, Federico

2016-01-01

Objective: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. Methods: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). Results: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. Conclusions: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes. PMID:27281533

Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy

PubMed Central

Kanaan, Nicholas M.; Cox, Kristine; Alvarez, Victor E.; Stein, Thor D.; Poncil, Sharra; McKee, Ann C.

2016-01-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. PMID:26671985

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

PubMed

Dermaut, B; Seneca, S; Dom, L; Smets, K; Ceulemans, L; Smet, J; De Paepe, B; Tousseyn, S; Weckhuysen, S; Gewillig, M; Pals, P; Parizel, P; De Bleecker, J L; Boon, P; De Meirleir, L; De Jonghe, P; Van Coster, R; Van Paesschen, W; Santens, P

2010-01-01

m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

 Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

PubMed

Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

2016-01-01

 Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

SCN2A encephalopathy

PubMed Central

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

2015-01-01

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

A woman with thyrotoxicosis- and hyperemesis gravidarum-associated Wernicke's encephalopathy.

PubMed

Anaforoğlu, İnan; Yildiz, Bülent; İnceçayir, Ömer; Algün, Ekrem

2012-01-01

Although hyperthyroidism arising from primary thyroid disease is rare in pregnancy, transient gestational hyperthyroidism is not uncommon. This condition can be associated with hyperemesis gravidarum (HG), and Wernicke's encephalopathy. We present the case of a woman with toxic nodular goiter complicating HG-associated Wernicke's encephalopathy. A 38-year-old Caucasian woman, who had received a diagnosis of hyperthyroidism and HG early in her pregnancy, had intrauterine fetal death at Week 16 of gestation. One day after undergoing therapeutic abortion, she was admitted to our clinic with persistent thyrotoxicosis, nausea, and vomiting. A toxic thyroid nodule was detected. She was given antithyroid medication, total parenteral nutrition. On Day 10 of hospitalization, she developed ataxia, aphasia, and somnolence. Cranial magnetic resonance imaging showed increased bilateral thalamic signalization. She was given a diagnosis of Wernicke's metabolic encephalopathy, for which she received thiamine and multivitamin preparations. She responded dramatically on the second day of thiamine therapy. Her consciousness improved rapidly and she began to speak. Her muscle tone was slightly weak and she had paresthesias in both legs. Absorption of thiamine may be particularly impaired in pregnant women with hyperemesis and hyperthyroid disease. Wernicke's encephalopathy should be considered in hyperthyroid women with HG who develop neurological abnormalities.

Risk factors and outcome of Shigella encephalopathy in Bangladeshi children.

PubMed

Afroze, Farzana; Ahmed, Tahmeed; Sarmin, Monira; Smsb Shahid, Abu; Shahunja, K M; Shahrin, Lubaba; Chisti, Mohammod Jobayer

2017-04-01

compared to those without encephalopathy. Early identification and aggressive management of simple risk factors for Shigella encephalopathy may help to reduce morbidity and deaths in such children especially in resource-limited settings.

Risk factors and outcome of Shigella encephalopathy in Bangladeshi children

PubMed Central

Afroze, Farzana; Ahmed, Tahmeed; Sarmin, Monira; SMSB Shahid, Abu; Shahunja, K. M.; Shahrin, Lubaba

2017-01-01

significantly higher among the children with Shigella encephalopathy compared to those without encephalopathy. Early identification and aggressive management of simple risk factors for Shigella encephalopathy may help to reduce morbidity and deaths in such children especially in resource-limited settings. PMID:28453565

Recent advances in hepatic encephalopathy

PubMed Central

DeMorrow, Sharon

2017-01-01

Hepatic encephalopathy describes the array of neurological alterations that occur during acute liver failure or chronic liver injury. While key players in the pathogenesis of hepatic encephalopathy, such as increases in brain ammonia, alterations in neurosteroid levels, and neuroinflammation, have been identified, there is still a paucity in our knowledge of the precise pathogenic mechanism. This review gives a brief overview of our understanding of the pathogenesis of hepatic encephalopathy and then summarizes the significant recent advances made in clinical and basic research contributing to our understanding, diagnosis, and possible treatment of hepatic encephalopathy. A literature search using the PubMed database was conducted in May 2017 using “hepatic encephalopathy” as a keyword, and selected manuscripts were limited to those research articles published since May 2014. While the authors acknowledge that many significant advances have been made in the understanding of hepatic encephalopathy prior to May 2014, we have limited the scope of this review to the previous three years only. PMID:29026534

Genetics Home Reference: CHD2 myoclonic encephalopathy

MedlinePlus

... Møller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, ... M, Accorsi P, Cappelletti S, Claps DJ, Vigevano F, Zara F, Specchio N. CHD2 mutations are a rare ...

Epileptic spasms and early-onset photosensitive epilepsy in Patau syndrome: An EEG study.

PubMed

Spagnoli, Carlotta; Kugathasan, Umaiyal; Brittain, Helen; Boyd, Stewart G

2015-08-01

Patau syndrome, trisomy 13, is the third commonest autosomal trisomy. It is associated with a 25-50% prevalence of epilepsy, but detailed electroclinical descriptions are rare. The occurrence of early-onset photosensitivity has recently been reported in single patients. We collected electroclinical data on 8 infants (age range from 2 months to 3 years and 9 months, median: 17 months) with Patau syndrome referred for an EEG in our Clinical Neurophysiology Department between 1991 and 2011. All EEGs, case-notes, cytogenetic diagnosis and neuroimaging when available were reviewed; data on the occurrence of seizures, epileptiform discharges, photoparoxysmal response and their characteristics in terms of positive frequencies, latencies, grade and duration were noted and analysed. Two patients had been previously diagnosed with epilepsy (one with tonic spasms and one with multiple seizure types). We found 3 patients with photosensitive myoclonic epilepsy (37.5%), and one with non-photosensitive myoclonic epilepsy. We also recorded non-epileptic myoclonic jerks in one patient known to suffer from epileptic spasms. Among photosensitive patients we found self-limited, Waltz's grade 2-4, spike-wave/polyspike-wave discharges in low, medium and high frequency ranges in two patients and in the high frequency range in the third patient, with latencies and duration from less than 1s to a maximum of 9s. In our cohort of Patau syndrome patients, we found a high prevalence of spasms and photic-induced myoclonic jerks. Photosensitivity shows an unusual early age of onset. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Food Safety: Bovine Spongiform Encephalopathy (Mad Cow Disease).

PubMed

Acheson, David W. K.

2002-01-01

Bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. Only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. Although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform encephalopathy in sheep, known as scrapie, is cause for concern. Further, bovine spongiform encephalopathy has now been strongly linked with a universally fatal human neurologic disease known as new variant Creutzfeldt-Jakob disease. Currently the only approach to preventing bovine spongiform encephalopathy, and subsequent new variant Creutzfeldt-Jakob disease in humans, from ingestion of bovine spongiform encephalopathy-infected material is to avoid consumption of contaminated food. Little can be done to treat food that will destroy prions and leave a palatable product. At this stage we are continuing to learn about transmissible spongiform encephalopathies and their implications on human health. This is an ever-changing situation and has an unpredictable element in terms of the extent of the current outbreaks in England and other parts of Europe.

Influenza-associated Encephalitis/Encephalopathy Identified by the Australian Childhood Encephalitis Study 2013-2015.

PubMed

Britton, Philip N; Dale, Russell C; Blyth, Christopher C; Macartney, Kristine; Crawford, Nigel W; Marshall, Helen; Clark, Julia E; Elliott, Elizabeth J; Webster, Richard I; Cheng, Allen C; Booy, Robert; Jones, Cheryl A

2017-11-01

Influenza-associated encephalitis/encephalopathy (IAE) is an important cause of acute encephalitis syndrome in children. IAE includes a series of clinicoradiologic syndromes or acute encephalopathy syndromes that have been infrequently reported outside East Asia. We aimed to describe cases of IAE identified by the Australian Childhood Encephalitis study. Children ≤ 14 years of age with suspected encephalitis were prospectively identified in 5 hospitals in Australia. Demographic, clinical, laboratory, imaging, and outcome at discharge data were reviewed by an expert panel and cases were categorized by using predetermined case definitions. We extracted cases associated with laboratory identification of influenza virus for this analysis; among these cases, specific IAE syndromes were identified where clinical and radiologic features were consistent with descriptions in the published literature. We identified 13 cases of IAE during 3 southern hemisphere influenza seasons at 5 tertiary children's hospitals in Australia; 8 children with specific acute encephalopathy syndromes including: acute necrotizing encephalopathy, acute encephalopathy with biphasic seizures and late diffusion restriction, mild encephalopathy with reversible splenial lesion, and hemiconvulsion-hemiplegia syndrome. Use of influenza-specific antiviral therapy and prior influenza vaccination were infrequent. In contrast, death or significant neurologic morbidity occurred in 7 of the 13 children (54%). The conditions comprising IAE are heterogeneous with varied clinical features, magnetic resonance imaging changes, and outcomes. Overall, outcome of IAE is poor emphasizing the need for optimized prevention, early recognition, and empiric management.

Experimental Interspecies Transmission Studies of the Transmissible Spongiform Encephalopathies to Cattle: Comparison to Bovine Spongiform Encephalopathy in Cattle

USDA-ARS?s Scientific Manuscript database

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...

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

PubMed

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-03-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant.

Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome.

PubMed

Chan, Derrick W S; Lim, C C Tchoyoson; Tay, Stacey K H; Choong, Chew-Thye; Phuah, Huan Kee

2007-06-01

Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with nonspecific encephalopathy. Hashimoto's encephalopathy is an association of steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies. Steroid-responsive encephalopathy, however, is not characteristic of the MELAS syndrome, which typically presents with stroke-like episodes and lactic acidosis in cerebrospinal fluid and blood. Here, a patient is described with goiter, recurrent encephalopathy and elevated thyroid peroxidase antibodies who apparently responded to steroid therapy; however, magnetic resonance imaging was atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS syndrome. This syndrome can present with apparent steroid-responsive encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's encephalopathy, and should be suspected if lactic acidosis is present and typical features are detected on magnetic resonance imaging.

[Hashimoto's encephalopathy and autoantibodies].

PubMed

Yoneda, Makoto

2013-04-01

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

[Post-partum posterior reversible encephalopathy syndrome].

PubMed

Aaen, Anne Albers; Jeppesen, Jørgen; Obaid, Hayder; Bülow, Hans Henrik

2015-11-23

Posterior reversible encephalopathy syndrome (PRES) is a complex clinical condition with vasogenic subcortical oedema caused by hypertension. Oedema is often seen on magnetic resonance imaging. The wide clinical spectrum ranges from headaches to vision loss and even death. Early diagnosis and treatment is important for the reversibility of the condition. In this case report we emphasize the importance of blood pressure control in a post-partum woman, who had a rather complicated pregnancy. The symptoms of PRES were not recognized immediately because of failure to use and acknowledge a blood pressure test.

Clinically mild infantile encephalopathy associated with excitotoxicity.

PubMed

Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Honda, Takafumi; Yasukawa, Kumi; Takanashi, Jun-Ichi

2017-02-15

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.

Hepatic encephalopathy in a liver transplant recipient with stable liver function.

PubMed

Arab, Juan Pablo; Meneses, Luis; Pérez, Rosa M; Arrese, Marco; Benítez, Carlos

2013-04-01

Postshunt hepatic encephalopathy after liver transplantation (LT) is an infrequent condition and is commonly associated with portal occlusion or stenosis and the presence of a patent portosystemic shunt. Portal vein stenosis (PVS) or thrombosis (PVT) are uncommon complications after LT. The overall frequency of both complications is reported to be less than 3%. When PVS or PVT develop early after LT, the occlusion of the portal vein can have catastrophic consequences to the graft including acute liver failure and graft loss. Late PVT/PVS are asymptomatic in approximately 50% of the cases and mainly diagnosed by a routine ultrasound. Symptomatic postshunt hepatic encephalopathy (HE) is a very infrequent condition after LT that has been scarcely reported in the literature. We present here the case of a liver recipient with normal graft function who presented with hepatic encephalopathy 3 months after LT with stable liver function but a severe portal stenosis and the presence of a spontaneous portosystemic shunt whose successful endovascular treatment was followed by the complete resolution of the HE.

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy

PubMed Central

Fehr, Stephanie; Wilson, Meredith; Downs, Jenny; Williams, Simon; Murgia, Alessandra; Sartori, Stefano; Vecchi, Marilena; Ho, Gladys; Polli, Roberta; Psoni, Stavroula; Bao, Xinhua; de Klerk, Nick; Leonard, Helen; Christodoulou, John

2013-01-01

The clinical understanding of the CDKL5 disorder remains limited, with most information being derived from small patient groups seen at individual centres. This study uses a large international data collection to describe the clinical profile of the CDKL5 disorder and compare with Rett syndrome (RTT). Information on individuals with cyclin-dependent kinase-like 5 (CDKL5) mutations (n=86) and females with MECP2 mutations (n=920) was sourced from the InterRett database. Available photographs of CDKL5 patients were examined for dysmorphic features. The proportion of CDKL5 patients meeting the recent Neul criteria for atypical RTT was determined. Logistic regression and time-to-event analyses were used to compare the occurrence of Rett-like features in those with MECP2 and CDKL5 mutations. Most individuals with CDKL5 mutations had severe developmental delay from birth, seizure onset before the age of 3 months and similar non-dysmorphic features. Less than one-quarter met the criteria for early-onset seizure variant RTT. Seizures and sleep disturbances were more common than in those with MECP2 mutations whereas features of regression and spinal curvature were less common. The CDKL5 disorder presents with a distinct clinical profile and a subtle facial, limb and hand phenotype that may assist in differentiation from other early-onset encephalopathies. Although mutations in the CDKL5 gene have been described in association with the early-onset variant of RTT, in our study the majority did not meet these criteria. Therefore, the CDKL5 disorder should be considered separate to RTT, rather than another variant. PMID:22872100

Clinical Characteristics of Transplant-associated Encephalopathy in Children.

PubMed

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

2017-03-01

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.

Clinical Characteristics of Transplant-associated Encephalopathy in Children

PubMed Central

2017-01-01

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

Analysis of Multiple B-Value Diffusion-Weighted Imaging in Pediatric Acute Encephalopathy

PubMed Central

Tachibana, Yasuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Kusagiri, Kouki; Mori, Kana; Endo, Kazuo; Obata, Takayuki; Inoue, Tomio

2013-01-01

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

Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy.

PubMed

Mei, Davide; Marini, Carla; Novara, Francesca; Bernardina, Bernardo D; Granata, Tiziana; Fontana, Elena; Parrini, Elena; Ferrari, Anna R; Murgia, Alessandra; Zuffardi, Orsetta; Guerrini, Renzo

2010-04-01

Mutations of the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause an X-linked encephalopathy with early onset intractable epilepsy, including infantile spasms and other seizure types, and a Rett syndrome (RTT)-like phenotype. Very limited information is available on the frequency and phenotypic spectrum associated with CDKL5 deletions/duplications. We investigated the role of CDKL5 deletions/duplications in causing early onset intractable epilepsy of unknown etiology in girls. We studied 49 girls with early onset intractable epilepsy, with or without infantile spasms, and developmental impairment, for whom no etiologic factors were obvious after clinical examination, brain magnetic resonance imaging (MRI) and expanded screening for inborn errors of metabolism. We performed CDKL5 gene mutation analysis in all and multiplex ligation dependent probe amplification assay (MLPA) in those who were mutation negative. Custom Array-comparative genomic hybridization (CGH), breakpoint polymerase chain reaction (PCR) analysis, and X-inactivation studies were performed in patients in whom MLPA uncovered a genomic alteration. We found CDKL5 mutations in 8.2% (4 of 49) of patients and genomic deletions in 8.2% (4 of 49). Overall, abnormalities of the CDKL5 gene accounted for 16.3% (8 of 49) of patients. CDKL5 gene deletions are an under-ascertained cause of early onset intractable epilepsy in girls. Genetic testing of CDKL5, including both mutation and deletion/duplication analysis, should be considered in this clinical subgroup.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

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

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study.

PubMed

Tann, Cally J; Nakakeeto, Margaret; Hagmann, Cornelia; Webb, Emily L; Nyombi, Natasha; Namiiro, Flaviah; Harvey-Jones, Kelly; Muhumuza, Anita; Burgoine, Kathy; Elliott, Alison M; Kurinczuk, Jennifer J; Robertson, Nicola J; Cowan, Frances M

2016-08-01

In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. Scans were performed at median age 11.5 (interquartile range (IQR): 5.2-20.2) and 8.4 (IQR: 3.6-13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98-9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61-6.95)). In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia-ischemia (HI). Early abnormalities were a significant predictor of death.

Genetics Home Reference: STXBP1 encephalopathy with epilepsy

MedlinePlus

... Conditions STXBP1 encephalopathy with epilepsy STXBP1 encephalopathy with epilepsy Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description STXBP1 encephalopathy with epilepsy is a condition characterized by recurrent seizures (epilepsy), ...

Gemifloxacin-associated neurotoxicity presenting as encephalopathy.

PubMed

Barrett, Matthew J; Login, Ivan S

2009-04-01

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.

Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: A case series and review of the literature.

PubMed

Mitani, Seiichiro; Kadowaki, Shigenori; Komori, Azusa; Sugiyama, Keiji; Narita, Yukiya; Taniguchi, Hiroya; Ura, Takashi; Ando, Masashi; Sato, Yozo; Yamaura, Hidekazu; Inaba, Yoshitaka; Ishihara, Makoto; Tanaka, Tsutomu; Tajika, Masahiro; Muro, Kei

2017-06-01

Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012. Eleven patients (0.6%) developed acute hyperammonemic encephalopathy. The incidence according to the administered anticancer drugs were as follows: 5-FU (8 of 1176, 0.7%), S-1 (1 of 679, 0.1%), capecitabine (2 of 225, 0.9%), and tegafur-uracil (UFT) (0 of 39, 0%). Ten patients (90.9%) had at least 1 aggravating factor, including infection, dehydration, constipation, renal dysfunction, and muscle loss. All the 10 patients met the definition of sarcopenia. Median time to the onset of hyperammonemic encephalopathy in the cycle was 3 days (range: 2-21). Three patients (27.3%) developed encephalopathy during the first cycle of the regimen and the remaining 8 patients during the second or more cycles. Seven patients (63.6%) had received at least 1 other FP-containing regimen before without episodes of encephalopathy.All patients recovered soon after immediate discontinuation of chemotherapy and supportive therapies, such as hydration, infusion of branched-chain amino acids, and oral lactulose intake, with a median time to recovery of 2 days (range: <1-7). Four patients (36.4%) received FP-based regimens after improvement of symptoms; 3 patients were successfully managed with dose reduction, and 1 patient, who had developed encephalopathy due to S-1 monotherapy, received modified FOLFOX-6 therapy without encephalopathy later.FP-associated acute hyperammonemic encephalopathy is extremely rare, but a possible event at any time and even

Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment?

PubMed

Mcintyre, Sarah; Badawi, Nadia; Blair, Eve; Nelson, Karin B

2015-04-01

Neonatal encephalopathy, a clinical syndrome affecting term-born and late preterm newborn infants, increases the risk of perinatal death and long-term neurological morbidity, especially cerebral palsy. With the advent of therapeutic hypothermia, a treatment designed for hypoxic or ischaemic injury, associated mortality and morbidity rates have decreased. Unfortunately, only about one in eight neonates (95% confidence interval) who meet eligibility criteria for therapeutic cooling apparently benefit from the treatment. Studies of infants in representative populations indicate that neonatal encephalopathy is a potential result of a variety of antecedents and that asphyxial complications at birth account for only a small percentage of neonatal encephalopathy. In contrast, clinical case series suggest that a large proportion of neonatal encephalopathy is hypoxic or ischaemic, and trials of therapeutic hypothermia are specifically designed to include only infants exposed to hypoxia or ischaemia. This review addresses the differences, definitional and methodological, between infants studied and investigations undertaken, in population studies compared with cooling trials. It raises the question if there may be subgroups of infants with a clinical diagnosis of hypoxic-ischaemic encephalopathy (HIE) in whom the pathobiology of neonatal neurological depression is not fundamentally hypoxic or ischaemic and, therefore, for whom cooling may not be beneficial. In addition, it suggests approaches to future trials of cooling plus adjuvant therapy that may contribute to further improvement of care for these vulnerable neonates. © The Authors. Journal compilation © 2015 Mac Keith Press.

Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy.

PubMed

Iannetti, Paola; Parisi, Pasquale; Spalice, Alberto; Ruggieri, Martino; Zara, Federico

2009-07-01

We report on the use of the voltage-gated calcium channel blocker (Vg-CCB), verapamil, as an add-on anticonvulsant medication in two girls, 4 and 14 years of age, who were affected by severe myoclonic epilepsy in infancy (SMEI) or Dravet syndrome, a channelopathy caused by abnormalities in the voltage-gated sodium channel neuronal type alpha1 subunit (SCN1A) gene at 2q24. Both girls had pharmacoresistant epilepsy and developmental delay. Mutation analysis for the SCN1A gene revealed a missense mutation in exon 2 in the 4-year-old girl. Verapamil was co-administered in both children with a prompt response in controlling status epilepticus, myoclonic jerks, and partial and generalized seizures. The therapeutic effect lasted 13 months in the 14-year-old girl, while it is still present after a 20-month follow-up period in the 4-year-old girl who, in addition, has experienced improvement in motor and language development. The verapamil vVg-CCB, which crosses the blood-brain barrier (BBB): (a) inhibits the P-glycoprotein, an active efflux transporter protein expressed in normal tissue, including the brain, which is believed to contribute to the in situ phenomenon of multidrug resistance; and (b) may regulate membrane depolarization induced by abnormal sodium channels functions by modulating the abnormal Ca++ influxes into neurons with subsequent cell resting. This is the first report on long-lasting verapamil therapy in SMEI. The functional consequences of such in vivo modulating effects on Ca++ channels could contribute to rational targeting for future molecular therapeutic approaches in pharmacoresistant epileptic channelopathies.

Metronidazole-induced encephalopathy in a patient with liver cirrhosis.

PubMed

Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul; Cho, Eun-Young

2011-06-01

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.

Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

PubMed

Zhang, Shuo; Feng, Juan; Shi, Yifang

2016-01-01

Infection with Epstein-Barr virus (EBV) is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical-radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Management and investigation of neonatal encephalopathy: 2017 update

PubMed Central

Martinello, Kathryn; Hart, Anthony R; Yap, Sufin; Mitra, Subhabrata

2017-01-01

This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the judicious use of investigations can help determine the cause. Over the last 7 years, infants with moderate to severe HIE have benefited from the introduction of routine therapeutic hypothermia; the number needed to treat for an additional beneficial outcome is 7 (95% CI 5 to 10). More recent research has focused on optimal resuscitation practices for babies with cardiorespiratory depression, such as delayed cord clamping after establishment of ventilation and resuscitation in air. Around a quarter of infants with asystole at 10 min after birth who are subsequently cooled have normal outcomes, suggesting that individualised decision making on stopping resuscitation is needed, based on access to intensive treatment unit and early cooling. The full benefit of cooling appears to have been exploited in our current treatment protocols of 72 hours at 33.5°C; deeper and longer cooling showed adverse outcome. The challenge over the next 5–10 years will be to assess which adjunct therapies are safe and optimise hypothermic brain protection in phase I and phase II trials. Optimal care may require tailoring treatments according to gender, genetic risk, injury severity and inflammatory status. PMID:28389438

QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease

PubMed Central

Guarani, Virginia; Jardel, Claude; Chrétien, Dominique; Lombès, Anne; Bénit, Paule; Labasse, Clémence; Lacène, Emmanuelle; Bourillon, Agnès; Imbard, Apolline; Benoist, Jean-François; Dorboz, Imen; Gilleron, Mylène; Goetzman, Eric S; Gaignard, Pauline; Slama, Abdelhamid; Elmaleh-Bergès, Monique; Romero, Norma B; Rustin, Pierre; Ogier de Baulny, Hélène; Paulo, Joao A; Harper, J Wade; Schiff, Manuel

2016-01-01

Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain function in patient muscle. QIL1 absence in patients’ fibroblasts was associated with MICOS disassembly, abnormal cristae, mild cytochrome c oxidase defect, and sensitivity to glucose withdrawal. QIL1 expression rescued cristae defects, and promoted re-accumulation of MICOS subunits to facilitate MICOS assembly. MICOS assembly and cristae morphology were not efficiently rescued by over-expression of other MICOS subunits in patient fibroblasts. Taken together, these data provide the first evidence of altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable MICOS complex formation. DOI: http://dx.doi.org/10.7554/eLife.17163.001 PMID:27623147

Clinical aspects of juvenile myoclonic epilepsy.

PubMed

Genton, Pierre; Thomas, Pierre; Kasteleijn-Nolst Trenité, Dorothee G A; Medina, Marco Tulio; Salas-Puig, Javier

2013-07-01

Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise. Copyright © 2013. Published by Elsevier Inc.

The transmissible spongiform encephalopathies of livestock

USDA-ARS?s Scientific Manuscript database

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...

Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

PubMed Central

John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

2017-01-01

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

Hepatic Encephalopathy

MedlinePlus Videos and Cool Tools

... People ALF Near You Events ALF Blogs Financial Information Policies Advocacy Patient Advisory Council Media Center Careers ... and abdomen (ascites) or hepatic encephalopathy. For more information about cirrhosis of the liver and symptoms, call ...

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study

PubMed Central

Tann, Cally J.; Nakakeeto, Margaret; Hagmann, Cornelia; Webb, Emily L.; Nyombi, Natasha; Namiiro, Flaviah; Harvey-Jones, Kelly; Muhumuza, Anita; Burgoine, Kathy; Elliott, Alison M.; Kurinczuk, Jennifer J.; Robertson, Nicola J.; Cowan, Frances M.

2016-01-01

Background: In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. Methods: Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. Results: Scans were performed at median age 11.5 (interquartile range (IQR): 5.2–20.2) and 8.4 (IQR: 3.6–13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98–9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61–6.95)). Conclusion: In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia–ischemia (HI). Early abnormalities were a significant predictor of death. PMID:27064242

Hypertensive brain stem encephalopathy.

PubMed

Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

2015-01-01

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.

LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.

PubMed

Stowe, Robert C; Sun, Qin; Elsea, Sarah H; Scaglia, Fernando

2018-05-01

Lipoic acid is an essential cofactor for the mitochondrial 2-ketoacid dehydrogenase complexes and the glycine cleavage system. Lipoyltransferase 1 catalyzes the covalent attachment of lipoate to these enzyme systems. Pathogenic variants in LIPT1 gene have recently been described in four patients from three families, commonly presenting with severe lactic acidosis resulting in neonatal death and/or poor neurocognitive outcomes. We report a 2-month-old male with severe lactic acidosis, refractory status epilepticus, and brain imaging suggestive of Leigh disease. Exome sequencing implicated compound heterozygous LIPT1 pathogenic variants. We describe the fifth case of LIPT1 deficiency, whose phenotype progressed to that of an early infantile epileptic encephalopathy, which is novel compared to previously described patients whom we will review. Due to the significant biochemical and phenotypic overlap that LIPT1 deficiency and mitochondrial energy cofactor disorders have with pyruvate dehydrogenase deficiency and/or nonketotic hyperglycinemia, they are and have been presumptively under-diagnosed without exome sequencing. © 2018 Wiley Periodicals, Inc.

Associations between birth at, or after, 41 weeks gestation and perinatal encephalopathy: a cohort study

PubMed Central

Yau, Christopher; Winter, Cathy; Draycott, Timothy; Rasmussen, Finn

2018-01-01

Background Preterm birth causes long-term problems, even for infants born 1 or 2 weeks early. However, less is known about infants born after their due date and over a quarter of infants are born over 1 week late, and many still remain undelivered after 2 weeks. The aim of this work is to quantify the risks of infants developing encephalopathy when birth occurs after the due date, and if other proposed risk factors modify this relationship. Methods The dataset contain information on 4 036 346 infants born in Sweden between 1973 and 2012. Exposure was defined as birth 7, or more, days after the infants’ due date. The primary outcome was the development of neonatal encephalopathy (defined as seizures, encephalopathy or brain injury caused by asphyxia or with unspecified cause). Covariates were selected as presumed confounders a priori. Results 28.4% infants were born 1 or more weeks after their due date. An infant’s risk of being born with encephalopathy was higher in the post 41 weeks group in the unadjusted (OR 1.40 (95% CI 1.32 to 1.49)) and final model (OR 1.38 (95% CI 1.29 to 1.47)), with the relative odds of encephalopathy increasing by an estimated 20% per week after the due date, and modified by maternal age (P=0.022). Conclusions Singleton infants born at, or after, 41 weeks gestation have lower Apgar scores and higher risk of developing encephalopathy in the newborn period, and the association appeared more marked in older mothers. These data could be useful if provided to women as part of their decision-making. PMID:29637179

Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment.

PubMed

Ware, Tyson L; Earl, John; Salomons, Gajja S; Struys, Eduard A; Peters, Heidi L; Howell, Katherine B; Pitt, James J; Freeman, Jeremy L

2014-05-01

Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal-5'-phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video-electroencephalographic (EEG) findings described. The first child showed electro-clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well-controlled epilepsy with pyridoxal-5'-phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal-5'-phosphate. At the age of 21 months he has global developmental delay and hemiparesis but is seizure-free with pyridoxal-5'-phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal-5'-phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal-5'-phosphate treatment cannot be relied upon to diagnose PNPO deficiency. © 2013 Mac Keith Press.

Gasoline sniffing and lead encephalopathy.

PubMed Central

Ross, C. A.

1982-01-01

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

The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology-related and developmental encephalopathies.

PubMed

Kalser, Judith; Cross, J Helen

2018-04-01

We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of 'developmental encephalopathy' which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful. The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.

Brain proton magnetic resonance spectroscopy for hepatic encephalopathy

NASA Astrophysics Data System (ADS)

Ong, Chin-Sing; McConnell, James R.; Chu, Wei-Kom

1993-08-01

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.

Surgical Treatment of Pediatric Epileptic Encephalopathies

PubMed Central

Fridley, J.; Reddy, G.; Curry, D.; Agadi, S.

2013-01-01

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

Electroencephalography and Brain MRI Patterns in Encephalopathy.

PubMed

Wabulya, Angela; Lesser, Ronald P; Llinas, Rafael; Kaplan, Peter W

2016-04-01

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.

Salivary lactate dehydrogenase levels can provide early diagnosis of hypoxic-ischaemic encephalopathy in neonates with birth asphyxia.

PubMed

Mehta, Akshay; Chawla, Deepak; Kaur, Jasbinder; Mahajan, Vidushi; Guglani, Vishal

2015-06-01

Timely detection of hypoxic-ischaemic encephalopathy (HIE) is crucial for selecting neonates who are likely to benefit from neuroprotective therapy. This study evaluated the efficacy of salivary lactate dehydrogenase (LDH) in the early diagnosis of HIE among neonates with perinatal asphyxia. We prospectively enrolled 30 neonates who needed resuscitation at birth or had a history of delayed cry into the HIE group if they developed HIE within 12 h of birth. The control group comprised 30 neonates who had no evidence of HIE, but had intrapartum foetal distress or needed resuscitation at birth. LDH was measured using saliva samples collected within 12 h of birth. Salivary LDH was significantly higher in the HIE group, with a median of 2578 and an interquartile range (IQR) of 1379-3408 international units per litre (IU/L), than in the control group (median 558.5, IQR: 348-924 IU/L, p < 0.001). The test demonstrated excellent discriminating ability: the area under the curve was 0.92 and the levels of 893 IU/L showed a sensitivity of 90% and a specificity of 73.3%. Measuring salivary LDH among neonates with birth asphyxia provided an early and accurate diagnosis of HIE and could be used as a triage tool. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Brain damage resembling acute necrotizing encephalopathy as a specific manifestation of haemophagocytic lymphohistiocytosis - induced by hypersensitivity.

PubMed

Dai, Dongling; Wen, Feiqiu; Liu, Sixi; Zhou, Shaoming

2016-08-31

Both haemophagocytic lymphohistiocytosis and acute necrotizing encephalopathy are life-threatening condition. It presents major diagnostic difficulties, since it may have a diversity in clinical picture and with many conditions leading to the same clinical presentation. So it is key important to understand the disorders. We report a pediatric case of haemophagocytic lymphohistiocytosis with specific presentation which predominantly featured as acute necrotizing encephalopathy of childhood. We discuss the diagnosis and differential diagnosis, and speculate the etiology of haemophagocytic lymphohistiocytosis is due to hypersensitivity. Haemophagocytic lymphohistiocytosis and brain damage in this case may be induced by hypersensitivity, which have good clinical outcome if diagnosed and treated early.

Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet.

PubMed

Hutcheon, Deborah A

2015-02-01

Wernicke's encephalopathy is a critical condition of neurological dysfunction resulting from a deficiency in thiamine. Chronic alcoholism is recognized as the most common cause of Wernicke's encephalopathy, but other causes, including fasting/starvation and malnutrition, have been documented within the scientific literature. These causes may not be readily recognized by healthcare professionals and may lead to Wernicke's encephalopathy being overlooked as a diagnosis when a nonalcoholic patient presents with classic signs and symptoms of the disorder. A narrative review of thiamine and its relationship to the development, diagnosis, and treatment of Wernicke's encephalopathy is presented based on a review of evidence-based guidelines and published research. To heighten awareness of the development of Wernicke's encephalopathy in fasted/starved and malnourished patients and to contribute to the scientific body of knowledge for the identification and management of Wernicke's encephalopathy in these patients, the clinical course and treatment of an adult woman who developed Wernicke's encephalopathy following a 40-day water-only fasting diet is outlined. Clinical suspicion was required to identify the patient's condition and initiate immediate intervention through parenteral thiamine administration. Oral thiamine supplementation of 100 to 800 mg per day for 6 months was required to aid recovery. The patient's clinical course and response to treatment illustrate the necessity for clinical awareness and suspicion of Wernicke's encephalopathy among healthcare professionals, timely and adequate parenteral thiamine administration, and oral thiamine supplementation at therapeutic doses to correct the nutrient deficiency, halt the progression of Wernicke's encephalopathy, and promote recovery. © 2014 American Society for Parenteral and Enteral Nutrition.

Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease

MedlinePlus

... the CDC Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease Note: Javascript is disabled or is not ... spongiform encephalopathy) is a progressive neurological disorder of cattle that results from infection by an unusual transmissible ...

Qualifying and quantifying minimal hepatic encephalopathy.

PubMed

Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A; Jackson, Clive D; Kircheis, Gerald; Lauridsen, Mette M; Montagnese, Sara; Schiff, Sami; Weissenborn, Karin

2016-12-01

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

Neurological and cognitive impairment associated with leaded gasoline encephalopathy.

PubMed

Cairney, Sheree; Maruff, Paul; Burns, Chris B; Currie, Jon; Currie, Bart J

2004-02-07

A toxic encephalopathy (or 'lead encephalopathy') may arise from leaded gasoline abuse that is characterised by tremor, hallucinations, nystagmus, ataxia, seizures and death. This syndrome requires emergency and intensive hospital treatment. We compared neurological and cognitive function between chronic gasoline abusers with (n=15) and without (n=15) a history of leaded gasoline encephalopathy, and with controls who had never abused gasoline (n=15). Both groups of chronic gasoline abusers had abused gasoline for the same length of time and compared to controls, showed equivalently elevated blood lead levels and cognitive abnormalities in the areas of visuo-spatial attention, recognition memory and paired associate learning. However, where gasoline abusers with no history of leaded gasoline encephalopathy showed only mild movement abnormalities, gasoline abusers with a history of leaded gasoline encephalopathy showed severe neurological impairment that manifest as higher rates of gait ataxia, abnormal rapid finger tapping, finger to nose movements, dysdiadochokinesia and heel to knee movements, increased deep tendon reflexes and presence of a palmomental reflex. While neurological and cognitive functions are disrupted by chronic gasoline abuse, leaded gasoline encephalopathy is associated with additional and long-lasting damage to cortical and cerebellar functions.

The myth of maternal transmission of spongiform encephalopathy.

PubMed Central

Ridley, R. M.; Baker, H. F.

1995-01-01

It has long been accepted that the pattern of occurrence of scrapie--the form of spongiform encephalopathy associated with sheep--is determined mainly by maternal transmission, and this view has had a profound influence on policy decisions in the control of bovine spongiform encephalopathy and on public concern over the risk to human health form this disease. The occurrence of maternal transmission is, however, not predicted by modern knowledge of the aetiology of spongiform encephalopathy, and even though claims of maternal transmission have been reiterated frequently in the literature, re-examination of the source data reveals that these data are extremely scanty, unreplicated, and probably subject to ascertainment bias. The probability of maternal transmission of spongiform encephalopathy in any species should be viewed with the greatest scepticism. Images p1073-a PMID:7580668

Dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide poisoning.

PubMed

Li, Q; Song, J J; Zhang, H Y; Fu, K; Lan, H B; Deng, Y

2015-01-01

We investigated dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide (CO) poisoning. Eighty healthy male rats were exposed to CO and randomly divided into four groups: hyperbaric oxygen treatment (H), treatment (D), combined hyperbaric and dexamethasone treatment (C), and a control (M) group in which the rats inhaled CO to coma in the hyperbaric oxygen chamber, then were removed without further treatment. Twelve rats were put into the hyperbaric oxygen chamber and treated with air for 60 min (N) group. An eight arm maze was used to evaluate cognitive and memory abilities of these mice. Serum myelin basic protein (MBP) levels were evaluated using ELISA, and magnetic resonance imaging was used to observe brain demyelination and morbidity associated with delayed encephalopathy. A sample of the hippocampus from each group was examined by light microscopy. Cognitive and memory functions decreased in the control group M. Three days after CO poisoning, the serum MBP level of each group increased significantly. On Day 10 after CO poisoning, the MBP levels in groups C and D decreased significantly, but returned to normal on Day 18. MBP levels in the M and H groups were elevated at all time points. Brain MRIs showed significant differences among C, D, H and control M groups. Hematoxylin & eosin staining of the hippocampus showed greater damage in the control M and H groups. Early dexamethasone treatment may be useful for preventing delayed encephalopathy after CO poisoning and may reduce serum MBP levels.

Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy

DTIC Science & Technology

2015-10-01

available, work will commence. Tau, genetics , susceptibility, MAPT, chronic traumatic encephalopathy, Alzheimer disease U U U U 1 USAMRMC Table of...AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy PRINCIPAL INVESTIGATOR: John F...Include area code) October 2015 Annual Report 30 Sep 2014 - 29 Sep 2015 Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy John

Reversible dementia with psychosis: Hashimoto's encephalopathy.

PubMed

Mocellin, Ramon; Lubman, Dan I; Lloyd, John; Tomlinson, E Bruce; Velakoulis, Dennis

2006-12-01

A case of presumed Hashimoto's encephalopathy (HE) is presented. The presentation included memory loss, delusions, functional decline and culminated in a generalized seizure. Anti-thyroid antibodies were detected and symptoms resolved with prednisolone. Patients with HE may present with prominent neuropsychiatric symptoms, attract psychiatric diagnoses and present to psychiatric services. Primarily a diagnosis of exclusion, HE should be considered in cases of encephalopathy in which standard investigations are negative.

The spectrum of disease in chronic traumatic encephalopathy.

PubMed

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

2013-01-01

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

The spectrum of disease in chronic traumatic encephalopathy

PubMed Central

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.

2013-01-01

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

Steroid-Responsive Recurrent Encephalopathy Associated with Subacute Thyroiditis

PubMed Central

Chung, Yun Jae; Ahn, Jihyun; Ha, Sam-Yeol; Youn, Young Chul

2008-01-01

Background Steroid-responsive encephalopathy associated with subacute thyroiditis has, to our knowledge, not been reported previously. Case Report A 49-year-old woman was found collapsed and brought to our institution with decreased mentality, dysarthria, and gait disturbance. Brain magnetic resonance imaging and angiography were normal but blood tests revealed thyroid-autoantibody-negative thyrotoxicosis. Results of a 99mtechnetium-pertechnetate scan were compatible with the thyrotoxic phase of subacute thyroiditis. 14-3-3 proteins were detected in cerebrospinal fluid. Her mental status began to improve from the day following steroid administration. Recurrent encephalopathy was found 2 months after the initial admission, which was also effectively treated with steroid. Conclusions We speculate that steroid-responsive recurrent encephalopathy associated with subacute thyroiditis is a subtype of Hashimoto's encephalopathy, and consider that steroid treatment should not be delayed in suspected patients. PMID:19513293

Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

PubMed

Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

2017-08-03

Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy.

PubMed

Walsh, Brian H; Neil, Jeffrey; Morey, JoAnn; Yang, Edward; Silvera, Michelle V; Inder, Terrie E; Ortinau, Cynthia

2017-08-01

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

Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

PubMed

Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

2017-11-01

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.

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

PubMed

Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

2018-07-01

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

Dengue-Associated Posterior Reversible Encephalopathy Syndrome, Vietnam

PubMed Central

Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Nghia, Ho Dang Trung; Phuong, Tran My; Duc, Du Trong; Chau, Nguyen Van Vinh; Wills, Bridget; Lim, Choie Cheio Tchoyoson; Thwaites, Guy; Simmons, Cameron Paul

2018-01-01

Dengue can cause neurologic complications in addition to the more common manifestations of plasma leakage and coagulopathy. Posterior reversible encephalopathy syndrome has rarely been described in dengue, although the pathophysiology of endothelial dysfunction likely underlies both. We describe a case of dengue-associated posterior reversible encephalopathy syndrome and discuss diagnosis and management. PMID:29350156

[Posterior reversible encephalopathy syndrome: Report of a fatal case and analysis of predictive factors of a poor prognosis].

PubMed

Torres, Moisés Ulises; Delgado, Ligia Victoria; Giraldo, Natalia; Urueña, Piedad; Franco, Sergio; Hernández, Olga Helena

2017-04-01

Posterior reversible encephalopathy syndrome is an illness with multiple causes and distinctive clinicalradiological characteristics that should be known by intensivists and emergency room physicians for a timely diagnosis and treatment. A fatal case of posterior reversible encephalopathy syndrome is presented, and the risk factors related to the outcome are identified.A 60-year-old man without a relevant medical history arrived at the emergency room presenting with depressed consciousness, seizures, and high blood pressure. Tomographic images revealed a posterior cerebellar hematoma. Resonance images showed ischemic zones, vasogenic edema from the thalamus to the brain stem, middle cerebellar peduncles, deep white matter of the cerebral hemispheres, and zones of hemorrhagic transformation. Despite medical-surgical management, the patient died. The risk factors described as the cause of the fatal outcome were identified. This case demonstrates that posterior reversible encephalopathy syndrome can occur without triggering risk factors and highlights the need for early recognition to establish an appropriate intervention to avoid injury or a fatal outcome. Cases of posterior reversible encephalopathy syndrome provide opportunities to investigate the susceptibility for the development of this condition and to establish appropriate preventive measures.

Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

USDA-ARS?s Scientific Manuscript database

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...

Evaluation and Management of Hepatic Encephalopathy: Current Status and Future Directions

PubMed Central

Suraweera, Duminda; Sundaram, Vinay; Saab, Sammy

2016-01-01

Hepatic encephalopathy is a spectrum of neurocognitive manifestations often seen in patients with liver injury or rarely in patients with portosystemic shunting without liver injury. It can be divided into minimal (covert) hepatic encephalopathy and overt hepatic encephalopathy, depending on the severity. Patients with hepatic encephalopathy have compromised clinical outcomes, decreased quality of life, and increased healthcare utilization, often resulting in a heavy financial and personal burden on caregivers. The diagnosis remains largely clinical, with the exclusion of possible other causes for the altered mental status. Current treatment strategies include nonabsorbable disaccharides and antibiotics. This review will focus on the diagnosis, management and clinical impact of hepatic encephalopathy. PMID:27377741

Clinical subtypes of chronic traumatic encephalopathy: literature review and proposed research diagnostic criteria for traumatic encephalopathy syndrome.

PubMed

Montenigro, Philip H; Baugh, Christine M; Daneshvar, Daniel H; Mez, Jesse; Budson, Andrew E; Au, Rhoda; Katz, Douglas I; Cantu, Robert C; Stern, Robert A

2014-01-01

The long-term consequences of repetitive head impacts have been described since the early 20th century. Terms such as punch drunk and dementia pugilistica were first used to describe the clinical syndromes experienced by boxers. A more generic designation, chronic traumatic encephalopathy (CTE), has been employed since the mid-1900s and has been used in recent years to describe a neurodegenerative disease found not just in boxers but in American football players, other contact sport athletes, military veterans, and others with histories of repetitive brain trauma, including concussions and subconcussive trauma. This article reviews the literature of the clinical manifestations of CTE from 202 published cases. The clinical features include impairments in mood (for example, depression and hopelessness), behavior (for example, explosivity and violence), cognition (for example, impaired memory, executive functioning, attention, and dementia), and, less commonly, motor functioning (for example, parkinsonism, ataxia, and dysarthria). We present proposed research criteria for traumatic encephalopathy syndrome (TES) which consist of four variants or subtypes (TES behavioral/mood variant, TES cognitive variant, TES mixed variant, and TES dementia) as well as classifications of 'probable CTE' and 'possible CTE'. These proposed criteria are expected to be modified and updated as new research findings become available. They are not meant to be used for a clinical diagnosis. Rather, they should be viewed as research criteria that can be employed in studies of the underlying causes, risk factors, differential diagnosis, prevention, and treatment of CTE and related disorders.

Rare and unusual ... or are they? Less commonly diagnosed encephalopathies associated with systemic disease.

PubMed

Weathers, Allison L; Lewis, Steven L

2009-04-01

Encephalopathy due to hepatic or renal failure, electrolyte disturbances, or the administration of benzodiazepines and narcotics is commonly encountered, well reviewed in the literature, and, therefore, not usually missed. This article focuses on encephalopathies that were previously well described but may be overlooked by modern clinicians, as well as those that are still taught in the classroom but seldom thought of in practice. Due to the presumed relative rarity of these cases and emphasis on the well-memorized "classic" clinical presentations, these often treatable, and perhaps not so rare, encephalopathies due to systemic medical illness may go undiagnosed and untreated. Pancreatic encephalopathy, Wernicke's encephalopathy, and pellagra encephalopathy are reviewed in detail; cefepime and ifosfamide encephalopathies are discussed as examples of specific medication-induced encephalopathies. Septic encephalopathy, central pontine myelinolysis, and fat embolism syndrome are briefly reviewed. The encephalopathies reviewed have the potential for devastating neurological consequences if recognition and, therefore, treatment are delayed. Clinical improvement for many of these syndromes depends on prompt intervention. This article highlights some representative examples of less-commonly diagnosed metabolic and toxic encephalopathies.

Radiographical findings in patients with liver cirrhosis and hepatic encephalopathy.

PubMed

Elwir, Saleh; Hal, Hassan; Veith, Joshua; Schreibman, Ian; Kadry, Zakiyah; Riley, Thomas

2016-08-01

Hepatic encephalopathy is a common complication encountered in patients with liver cirrhosis. Hepatic encephalopathy is not reflected in the current liver transplant allocation system. Correlation was sought between hepatic encephalopathy with findings detected on radiographic imaging studies and the patient's clinical profile. A retrospective analysis was conducted of patients with cirrhosis, who presented for liver transplant evaluation in 2009 and 2010. Patients with hepatocellular carcinoma, ejection fraction less than 60% and who had a TIPS (transjugular intrahepatic portosystemic shunting) procedure or who did not complete the evaluation were excluded. Statistical analysis was performed and variables found to be significant on univariate analysis (P < 0.05) were analysed by a multivariate logistic regression model. A total of 117 patients met the inclusion criteria and were divided into a hepatic encephalopathy group (n = 58) and a control group (n = 59). Univariate analysis found that a smaller portal vein diameter, smaller liver antero-posterior diameter, liver nodularity and use of diuretics or centrally acting medications showed significant correlation with hepatic encephalopathy. This association was confirmed for smaller portal vein, use of diuretics and centrally acting medications in the multivariate analysis. A decrease in portal vein diameter was associated with increased risk of encephalopathy. Identifying patients with smaller portal vein diameter may warrant screening for encephalopathy by more advanced psychometric testing, and more aggressive control of constipation and other factors that may precipitate encephalopathy. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Subacute Noninfective Inflammatory Encephalopathy: Our Experience and Diagnostic Problems

PubMed Central

Chandra, Sadanandavalli Retnaswami; Viswanathan, Lakshminarayanapuram Gopal; Sindhu, Dodmalur Malikarjuna; Pai, Anupama Ramakanth

2017-01-01

Introduction: Immune dysregulation associated encephalopathies present with significant psychiatric manifestations and only a few soft neurological and general systemic features. They are generally resistant to treatment with psychiatric medications. Generalized orthostatic myoclonus and faciobrachial dystonic seizures are mistaken as Creutzfeldt-Jakob disease and subacute sclerosing panencephalitis. Patients and Methods: Forty-two patients seen during 2010–2015 and diagnosed as noninfective encephalopathy were analyzed. Those patients with infective causes and those who had significant features of systemic manifestations of vasculitis and other disorders of central nervous system were excluded from the study. They were investigated with cerebrospinal fluid imaging, electroencephalogram (EEG), and antibody profile. Results: More than 70% patients had psychiatric manifestation as presenting features and reported to psychiatrist. Three patients had paraneoplastic and others N-methyl-D-aspartate, voltage-gated potassium channel, thyroid peroxidase, antinuclear antibody related, and few were due to unknown antibody. Conclusion: Serious diagnostic errors are common and early diagnosis is based on high degree suspicion in patients presenting with new-onset refractory psychosis. Soft neurological features should be looked for and EEG serves as a very sensitive tool in establishing organicity. PMID:28515556

Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy.

PubMed

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

2016-03-01

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.

Bovine spongiform encephalopathy: "mad cow disease".

PubMed

1996-07-01

Bovine spongiform encephalopathy (BSE), also known as "mad cow disease," is a fatal brain disease of cattle first recognized in the United Kingdom. In humans, the most common transmissible spongiform encephalopathy is Creutzfeldt-Jacob Disease (CJD). Although no cases of CJD have been directly linked to beef consumption, an advisory committee has reported that 10 recent cases of a CJD variant may be associated with BSE. This announcement has alarmed consumers well beyond the borders of the United Kingdom.

Clinical review of genetic epileptic encephalopathies

PubMed Central

Noh, Grace J.; Asher, Y. Jane Tavyev; Graham, John M.

2012-01-01

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

Cognitive Outcomes After Neonatal Encephalopathy

PubMed Central

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.

2015-01-01

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

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.

PubMed

Dilena, Robertino; Striano, Pasquale; Traverso, Monica; Viri, Maurizio; Cristofori, Gloria; Tadini, Laura; Barbieri, Sergio; Romeo, Antonino; Zara, Federico

2016-01-01

Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery. We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein. The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Topiramate increases the risk of valproic acid-induced encephalopathy.

PubMed

Noh, Young; Kim, Dong Wook; Chu, Kon; Lee, Soon-Tae; Jung, Keun-Hwa; Moon, Hye-Jin; Lee, Sang Kun

2013-01-01

Metabolic encephalopathy is a rare but serious complication of valproic acid (VPA) therapy that usually presents with impaired consciousness or increased seizure frequency. Although it has been suggested that topiramate (TPM) increases the risk of VPA-induced encephalopathy, the additional risk in patients receiving TPM therapy has not been evaluated. We reviewed all adult patients who took VPA between January 2005 and February 2009 at the Seoul National University Hospital and identified patients with VPA-induced encephalopathy based on clinical and electroencephalography (EEG) data. Information on sex, age, serum ammonia level, serum VPA level, liver function test, and EEG was collected from patient registry and medical data. We enrolled 8,372 patients who received VPA therapy and 1,236 patients who received VPA/TPM combination therapy. We identified 11 patients with VPA-induced encephalopathy (0.13%), 7 of whom received a combination therapy of VPA and TPM. The odds ratio of VPA-induced encephalopathy with TPM over that without TPM was 10.16. There were no significant differences in sex distribution, number of antiepileptic agents, ammonia level, VPA serum level, underlying diseases, dosage of VPA, duration of VPA treatment, treatment of encephalopathy, and outcomes between the two groups. Our study showed that the prevalence of VPA-induced encephalopathy is approximately 0.1% among patients treated with VPA and that the risk of this condition, although still low, can increase by approximately 10 times in the presence of TPM therapy. Based on these results, we suggest that TPM should be carefully used in patients receiving VPA treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Hepatic encephalopathy in acute-on-chronic liver failure.

PubMed

Lee, Guan-Huei

2015-10-01

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.

Clinical manifestations and treatment response of steroid in pediatric Hashimoto encephalopathy.

PubMed

Yu, Hee Joon; Lee, Jeehun; Seo, Dae Won; Lee, Munhyang

2014-07-01

Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with elevated titers of antithyroid antibodies. Clinical symptoms are characterized by behavioral and cognitive changes, speech disturbance, seizures, myoclonus, psychosis, hallucination, involuntary movements, cerebellar signs, and coma. The standard treatment is the use of corticosteroids along with the treatment of any concurrent dysthyroidism. Other options are immunoglobulins and plasmapheresis. We described symptoms and outcomes on 3 teenage girls with Hashimoto encephalopathy. Presenting symptoms were seizure or altered mental status. One patient took levothyroxine due to hypothyroidism before presentation of Hashimoto encephalopathy. After confirmation of elevated antithyroid antibodies, all patients were treated with steroids. One patient needed plasmapheresis because of the lack of response to steroids and immunoglobulins. Hashimoto encephalopathy should be considered in any patient presenting with acute or subacute unexplained encephalopathy and seizures. Even though the use of steroids is the first line of treatment, plasmapheresis can rescue steroid-resistant patients. © The Author(s) 2013.

Baclofen-induced encephalopathy in overdose - Modeling of the electroencephalographic effect/concentration relationships and contribution of tolerance in the rat.

PubMed

Chartier, Magali; Malissin, Isabelle; Tannous, Salma; Labat, Laurence; Risède, Patricia; Mégarbane, Bruno; Chevillard, Lucie

2018-05-18

Baclofen, a γ-amino-butyric acid type-B receptor agonist with exponentially increased use at high-dose to facilitate abstinence in chronic alcoholics, is responsible for increasing poisonings. Baclofen overdose may induce severe encephalopathy and electroencephalographic (EEG) abnormalities. Whether prior prolonged baclofen treatment may influence the severity of baclofen-induced encephalopathy in overdose has not been established. We designed a rat study to characterize baclofen-induced encephalopathy, correlate its severity with plasma concentrations and investigate the contribution of tolerance. Baclofen-induced encephalopathy was assessed using continuous EEG and scored based on a ten-grade scale. Following the administration by gavage of 116 mg/kg baclofen, EEG rapidly and steadily impaired resulting in the successive onset of deepening sleep followed by generalized periodic epileptiform discharges and burst-suppressions. Thereafter, encephalopathy progressively recovered following similar phases in reverse. Periodic triphasic sharp waves, non-convulsive status epilepticus and even isoelectric signals were observed at the most critical stages. Prior repeated baclofen administration resulted in reduced severity (peak: grade 7 versus 9; peak effect length: 382 ± 40 versus 123 ± 14 min, P = 0.008) and duration of encephalopathy (18 versus > 24 h, P = 0.0007), supporting the acquisition of tolerance. The relationship between encephalopathy severity and plasma baclofen concentrations fitted a sigmoidal E max model with an anticlockwise hysteresis loop suggesting a hypothetical biophase site of action. The baclofen concentration producing a response equivalent to 50% of E max was significantly reduced (8947 μg/L, ±11.3% versus 12,728 μg/L, ±24.0% [mean, coefficient of variation], P = 0.03) with prior prolonged baclofen administration. In conclusion, baclofen overdose induces early-onset and prolonged marked encephalopathy

CADASIL: Migraine, Encephalopathy, Stroke and Their Inter-Relationships.

PubMed

Tan, Rhea Yan Ying; Markus, Hugh Stephen

2016-01-01

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

Genetics Home Reference: familial encephalopathy with neuroserpin inclusion bodies

MedlinePlus

... Home Health Conditions FENIB Familial encephalopathy with neuroserpin inclusion bodies Printable PDF Open All Close All Enable ... expand/collapse boxes. Description Familial encephalopathy with neuroserpin inclusion bodies ( FENIB ) is a disorder that causes progressive ...

Relationship between clock and star drawing and the degree of hepatic encephalopathy.

PubMed

Edwin, Natasha; Peter, John Victor; John, George; Eapen, C E; Graham, Petra L

2011-09-01

PURPOSE OF THE STUDY Current hepatic encephalopathy grading tools are limited because of complexity or subjectivity. The degree of constructional apraxia could serve as a simple, objective and reproducible tool to grade encephalopathy. STUDY DESIGN In this cross-sectional study of patients with chronic liver disease, the degree of constructional apraxia was judged by their ability to copy a star and clock face and compared with conventional encephalopathy grading by the West Haven Criteria (WHC) and the Porto Systemic Encephalopathy Index (PSEI). Three blinded observers independently graded the figures. Sensitivity, specificity and positive predictive value (PPV) of clock and star scores (score 0 implying no encephalopathy and >0 hepatic encephalopathy) were assessed against conventional scoring systems (WHC grade >0 or PSEI ≥0.33 indicating encephalopathy). Mosaic and box plots were generated to assess if the degree of constructional apraxia correlated with the severity of encephalopathy. RESULTS 71 patients were studied between October 2008 and July 2009; 11 (15.4%) had WHC grade 0, 32 (45%) grade 1, and 28 (39.4%) grades 2 and 3 encephalopathy. The sensitivity, specificity and PPV of the clock drawing for the diagnosis of encephalopathy was 85%, 80%, and 96%, respectively, and 77%, 70%, and 94%, respectively, for the star drawing. Box plots and intervals on mean PSEI showed an increasing relationship between clock/star scores and PSEI. There was substantial agreement between WHC and clock (weighted κ 0.61) and star scores (weighted κ 0.71). Inter-observer reliability was at least 0.70 for star and at least 0.79 for the clock score. CONCLUSION Clock and star drawing may serve as reproducible, inexpensive bedside tools for diagnosing and grading the severity of hepatic encephalopathy.

Progressive myoclonic epilepsies: definitive and still undetermined causes.

PubMed

Franceschetti, Silvana; Michelucci, Roberto; Canafoglia, Laura; Striano, Pasquale; Gambardella, Antonio; Magaudda, Adriana; Tinuper, Paolo; La Neve, Angela; Ferlazzo, Edoardo; Gobbi, Giuseppe; Giallonardo, Anna Teresa; Capovilla, Giuseppe; Visani, Elisa; Panzica, Ferruccio; Avanzini, Giuliano; Tassinari, Carlo Alberto; Bianchi, Amedeo; Zara, Federico

2014-02-04

To define the clinical spectrum and etiology of progressive myoclonic epilepsies (PMEs) in Italy using a database developed by the Genetics Commission of the Italian League against Epilepsy. We collected clinical and laboratory data from patients referred to 25 Italian epilepsy centers regardless of whether a positive causative factor was identified. PMEs of undetermined origins were grouped using 2-step cluster analysis. We collected clinical data from 204 patients, including 77 with a diagnosis of Unverricht-Lundborg disease and 37 with a diagnosis of Lafora body disease; 31 patients had PMEs due to rarer genetic causes, mainly neuronal ceroid lipofuscinoses. Two more patients had celiac disease. Despite extensive investigation, we found no definitive etiology for 57 patients. Cluster analysis indicated that these patients could be grouped into 2 clusters defined by age at disease onset, age at myoclonus onset, previous psychomotor delay, seizure characteristics, photosensitivity, associated signs other than those included in the cardinal definition of PME, and pathologic MRI findings. Information concerning the distribution of different genetic causes of PMEs may provide a framework for an updated diagnostic workup. Phenotypes of the patients with PME of undetermined cause varied widely. The presence of separate clusters suggests that novel forms of PME are yet to be clinically and genetically characterized.

Prediction of Early Childhood Outcome of Term Infants using Apgar Scores at 10 Minutes following Hypoxic-Ischemic Encephalopathy

PubMed Central

Laptook, Abbot R.; Shankaran, Seetha; Ambalavanan, Namasivayam; Carlo, Waldemar A.; McDonald, Scott A.; Higgins, Rosemary D.; Das, Abhik

2010-01-01

Context Death or severe disability is so common following an Apgar score of 0 at 10 minutes in observational studies that the Neonatal Resuscitation Program suggests considering discontinuation of resuscitation after 10 minutes of effective CPR. Objective To determine if Apgar scores at 10 minutes are associated with death or disability in early childhood following perinatal hypoxic-ischemic encephalopathy (HIE). Design, Setting, and Patients This is a secondary analysis of infants enrolled in the NICHD Neonatal Research Network hypothermia trial. Infants ≥ 36 weeks gestation had clinical and/or biochemical abnormalities at birth, and encephalopathy at < 6 hours. Logistic regression and classification and regression tree (CART) analysis was used to determine associations between Apgar scores at 10 minutes and neurodevelopmental outcome adjusting for covariates. Associations are expressed as odds ratios (OR) and 95% confidence interval (CI). Main Outcome Measure Death or disability (moderate or severe) at 18–22 months of age. Results Twenty of 208 infants were excluded (missing data). More than 90% of infants had Apgar scores of 0–2 at 1 minute and Apgars at 5 and 10 minutes shifted to progressively higher values; at 10 minutes 27% of infants had Apgar scores of 0–2. After adjustment each point decrease in Apgar score at 10 minutes was associated with a 45% increase in the odds of death or disability (OR 1.45, CI 1.22–1.72). Death or disability occurred in 76, 82 and 80% of infants with Apgar scores at 10 minutes of 0, 1 and 2, respectively. CART analysis indicated that Apgar scores at 10 minutes were discriminators of outcome. Conclusion Apgar scores at 10 minutes provide useful prognostic data before other evaluations are available for infants with HIE. Death or moderate/severe disability is common but not uniform with Apgar scores < 3; caution is needed before adopting a specific time interval to guide duration of resuscitation. PMID:19948631

The Spectrum of Disease in Chronic Traumatic Encephalopathy

ERIC Educational Resources Information Center

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.

2013-01-01

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…

Glucose metabolism transporters and epilepsy: only GLUT1 has an established role.

PubMed

Hildebrand, Michael S; Damiano, John A; Mullen, Saul A; Bellows, Susannah T; Oliver, Karen L; Dahl, Hans-Henrik M; Scheffer, Ingrid E; Berkovic, Samuel F

2014-02-01

The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later-onset generalized epilepsies and paroxysmal exercise-induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy-causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Impact of Perinatal Systemic Hypoxic–Ischemic Injury on the Brain of Male Offspring Rats: An Improved Model of Neonatal Hypoxic–Ischemic Encephalopathy in Early Preterm Newborns

PubMed Central

Xu, Hongwu; Wu, Weizhao; Lai, Xiulan; Ho, Guyu; Ma, Lian; Chen, Yunbin

2013-01-01

In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE) in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND) 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions. PMID:24324800

A case of fulminant subacute sclerosing panencephalitis presenting with acute myoclonic-astatic epilepsy.

PubMed

Magurano, Fabio; Marella, Gian Luca; Marchi, Antonella; Filia, Antonietta; Marsella, Luigi Tonino; Potenza, Saverio; Massa, Roberto; Bucci, Paola; Baggieri, Melissa; Nicoletti, Loredana

2017-01-01

The neurologic sequelae post-measles are less common than other complications measles-related and can lead to severe disability or death: primary measles encephalitis (PME), acute post-infectious measles encephalomyelitis (APME), measles inclusion body encephalitis (MIBE), and subacute sclerosing panencephalitis (SSPE). SSPE syndrome can affect people years from the acute measles virus infection, as result of the persistence of defective viral particles in brain cells. Clinical onset typically manifests with progressive intellectual deterioration, behavioral changes, and myoclonic jerks. The course of SSPE in the majority of affected children is that of a progressive worsening with fatal outcome within two years. This report described an Italian case of fulminant SSPE syndrome that led to death within few months from the initial onset.

Segregation analysis of juvenile myoclonic epilepsy

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

Weissbecker, K.A.; Delgado-Escueta, A.V.; Medina, M.T.

1994-09-01

Juvenile myoclonic epilepsy (JME) is a non-progressive epilepsy characterized by involuntary jerks and an adolescent age of onset. There conflicting reports regarding the mode of inheritance of JME - polygenic, autosomal recessive, and two-locus models have all been proposed. We performed a segregation analysis of 53 nuclear families of JME probands using the Elston and Stewart algorithm (S.A.G.E version 2.1). Relatives of the proband were classified as affected if they had a confirmed history of JME, absence or grand mal epilepsy, or if they were clinically asymptomatic but had 3.5-6 Hz multispike wave complexes on electroencephalography. Using these criteria, 40more » relatives were affected in addition to the 53 probands. All Mendelian models were rejected when compared to the unrestricted model which estimated transmission probabilities. The environmental models were also rejected. Of the Mendelian modes, the most parsimonious model was the autosomal recessive model with 53% penetrance and a rate of sporadic cases of 0.0039. We conclude that although there is evidence for a genetic component contributing to the familiality of JME, this component can not be explained by a single major gene. These results, along with contradictory reports regarding the linkage of JME to the short arm of chromosome 6, suggest the presence of genetic heterogeneity and/or a more complex mode of inheritance, such as a two-locus model. Since lod score linkage analyses are dependent on the assumption of a single major gene mode, these findings emphasize the necessity of performing non-parametric linkage analyses when studying JME.« less

Risky Decision Making in Juvenile Myoclonic Epilepsy.

PubMed

Unterberger, Iris; Zamarian, Laura; Prieschl, Manuela; Bergmann, Melanie; Walser, Gerald; Luef, Gerhard; Javor, Andrija; Ransmayr, Gerhard; Delazer, Margarete

2018-01-01

It is not known whether patients with juvenile myoclonic epilepsy (JME) differ from healthy people in decision making under risk, i.e., when the decision-making context offers explicit information about options, probabilities, and consequences already from the beginning. In this study, we adopted the Game of Dice Task-Double to investigate decision making under risk in a group of 36 patients with JME (mean age 25.25/SD 5.29 years) and a group of 38 healthy controls (mean age 26.03/SD 4.84 years). Participants also underwent a comprehensive neuropsychological assessment focused on frontal executive functions. Significant group differences were found in tests of psychomotor speed and divided attention, with the patients scoring lower than the controls. Importantly, patients made risky decisions more frequently than controls. In the patient group, poor decision making was associated with poor executive control, poor response inhibition, and a short interval since the last seizure episode. Executive control and response inhibition could predict 42% of variance in the frequency of risky decisions. This study indicates that patients with JME with poorer executive functions are more likely to make risky decisions than healthy controls. Decision making under risk is of major importance in every-day life, especially with regard to treatment decisions and adherence to long-term medical therapy. Since even a single disadvantageous decision may have long-lasting consequences, this finding is of high relevance.

77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... Spongiform Encephalopathy; Importation of Bovines and Bovine Products AGENCY: Animal and Plant Health... derived from bovines with regard to bovine spongiform encephalopathy. This action will allow interested... importation of live bovines and products derived from bovines with regard to bovine spongiform encephalopathy...

Genetics Home Reference: SCN8A-related epilepsy with encephalopathy

MedlinePlus

... epilepsy with encephalopathy . This condition is estimated to account for 1 percent of all cases of epilepsy with encephalopathy. Related Information What information about a genetic condition can statistics ...

Evaluation of the zoonotic potential of transmissible mink encephalopathy

USDA-ARS?s Scientific Manuscript database

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...

Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with Hypothermia

PubMed Central

Massaro, An N.; Chang, Taeun; Kadom, Nadja; Tsuchida, Tammy; Scafidi, Joseph; Glass, Penny; McCarter, Robert; Baumgart, Stephen; Vezina, Gilbert; Nelson, Karin B.

2012-01-01

Objective To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy. Study design Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7–10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis. Results Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5–7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures. Conclusion Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. PMID:22494878

Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia.

PubMed

Massaro, An N; Chang, Taeun; Kadom, Nadja; Tsuchida, Tammy; Scafidi, Joseph; Glass, Penny; McCarter, Robert; Baumgart, Stephen; Vezina, Gilbert; Nelson, Karin B

2012-09-01

To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy. Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7-10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis. Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5-7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures. Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. Copyright © 2012 Mosby, Inc. All rights reserved.

The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

PubMed

Zerem, Ayelet; Haginoya, Kazuhiro; Lev, Dorit; Blumkin, Lubov; Kivity, Sara; Linder, Ilan; Shoubridge, Cheryl; Palmer, Elizabeth Emma; Field, Michael; Boyle, Jackie; Chitayat, David; Gaillard, William D; Kossoff, Eric H; Willems, Marjolaine; Geneviève, David; Tran-Mau-Them, Frederic; Epstein, Orna; Heyman, Eli; Dugan, Sarah; Masurel-Paulet, Alice; Piton, Ame'lie; Kleefstra, Tjitske; Pfundt, Rolph; Sato, Ryo; Tzschach, Andreas; Matsumoto, Naomichi; Saitsu, Hirotomo; Leshinsky-Silver, Esther; Lerman-Sagie, Tally

2016-11-01

IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical

Determination of lactic acid level in systemic liquids in children with progressive encephalopathies.

PubMed

Marszał, Elzbieta; Wojaczyńska-Stanek, Katarzyna; Pietruszewski, Jerzy; Emich-Widera, Ewa; Bielińska-Bujniewicz, Eugenia

2002-03-01

This article reports the results of research into the activities of lactic acid concentrations in the body fluids of children with progressive encephalopathies (PE) in comparison to patients with non-progressive encephalopathies (NPE) and those with non-progressive encephalopathies with concomitant epilepsy (NPEE). The study was designed to determine whether there is difference between the serum and CSF lactic acid concentrations in children with progressive encephalopathies (PE), static (non-progressive) encephalopathies (NPE) and non progressive encephalopathies with concomitant epilepsy (NPEE), and whether the clinical status correlates with the concentration of these biochemical markers in children with PE. The assessment involved 138 children of both sexes, whose age ranged between 8 months and 15 years, diagnosed and treated in the Neurology Department at the Pediatric Clinic of the Silesian Medical Academy in Katowice between 1995 and 1997. Lactate concentrations were determined in serum and cerebro-spinal fluid and analyzed statistically. The findings showed higher serum and CSF concentrations in children with PE than in patients who manifested non-progressive forms of encephalopathy. The degree of clinical symptom aggravation in PE children was likewise analyzed and compared to the values of lactate concentrations in body fluids; however, no correlation was found between these parameters. Children with progressive encephalopathies present higher lactate concentrations in serum and cerebrospinal fluid than patients with static (non-progressive) encephalopathy.

Neuropathology of italian cats in feline spongiform encephalopathy surveillance.

PubMed

Iulini, B; Cantile, C; Mandara, M T; Maurella, C; Loria, G R; Castagnaro, M; Salvadori, C; Porcario, C; Corona, C; Perazzini, A Z; Maroni, A; Caramelli, M; Casalone, C

2008-09-01

Feline spongiform encephalopathy (FSE) is a transmissible spongiform encephalopathy associated with the consumption of feedstuffs contaminated with tissue from bovine spongiform encephalopathy-affected cattle and characterized by the accumulation in the central nervous system of an abnormal isoform of the prion protein (PrP(sc)). Clinically, it presents as a progressive fatal neurologic syndrome that is not easily distinguished from other feline neurologic conditions. Most cases of FSE have been reported in England, where it was first detected in 1990, but a few cases have been reported from other European countries. To identify possible cases of FSE in Italy, the Italian Ministry of Health funded a 2-year surveillance project during which the brains from 110 domestic cats with neurologic signs were evaluated histologically for spongiform encephalopathy and immunohistochemically to detect PrP(sc). Although no cases of FSE were found, the study proved useful in monitoring the Italian cat population for other neurologic diseases: neoplasia (21.8%), toxic-metabolic encephalopathy (18.2%), granulomatous encephalitis (15.5%), suppurative encephalitis (4.6%), trauma (3.6%), circulatory disorders (3.6%), degeneration (2.7%), nonsuppurative encephalitis (2.7%), and neuromuscular diseases (1.8%). No histologic lesions were found in 20% of the brains, and samples from 5.5% of the cats were rejected as unsuitable.

The Aicardi-Goutières syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis).

PubMed Central

Tolmie, J L; Shillito, P; Hughes-Benzie, R; Stephenson, J B

1995-01-01

Aicardi-Goutières syndrome (Mendelian inheritance in man Catalog No *225750) is an autosomal recessive encephalopathy which causes developmental arrest, intracerebral calcification, and white matter disease in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid interferon-alpha (IFN-alpha). Diagnosis requires the presence of progressive encephalopathy with onset shortly after birth, and characteristic clinical neurological and neuroimaging signs together with chronic CSF lymphocytosis. The syndrome has superficial resemblance to the neurological sequelae of congenital infection, thus a rigorous search for microbiological and serological evidence of embryopathic infections should be carried out in each case. Images PMID:8592332

Dyscirculatory encephalopathy in Chernobyl disaster clean-up workers (a 20-year study).

PubMed

Podsonnaya, I V; Shumakher, G I; Golovin, V A

2010-05-01

Results obtained over 20-years of following 536 Chernobyl clean-up workers and 436 control subjects are presented. Dyscirculatory encephalopathy developed more frequently in persons exposed to radiation at age 30 years. As compared with the control group, workers were characterized by early onset of disease, faster progression, stable symptomatology for 5-6 years, and further progression of disease in the form of autonomic dysfunction, psycho-organic syndrome, and epilepsy. Major strokes were also more common in clean-up workers.

Reversible splenial lesion syndrome associated with encephalitis/encephalopathy presenting with great clinical heterogeneity.

PubMed

Zhu, Yuanzhao; Zheng, Junjun; Zhang, Ling; Zeng, Zhenguo; Zhu, Min; Li, Xiaobin; Lou, Xiaoliang; Wan, Hui; Hong, Daojun

2016-04-18

Reversible splenial lesion syndrome (RESLES) is a disorder radiologically characterized by reversible lesion in the splenium of the corpus callosum (SCC). Most of patients with RESLES associated with encephalitis/encephalopathy were identified in Japanese population, but almost no Chinese patients were diagnosed as RESLES associated with encephalitis/encephalopathy. Possible patients with reversible isolated SCC lesions were retrieved from January 2012 to July 2015 using keyword "restricted diffusion and isolated SCC lesion" in MRI report system from a large academic center. The clinical, laboratory and radiological data were summarized. A total of 15 encephalitis/encephalopathy patients (9 males and 6 females) were identified with a reversible isolated SCC lesion. Except for 13 patients with fever symptom, 8 patients also had cold symptoms before the onset of neurological symptoms. The neurological symptoms included headache, vertigo, seizure, disturbance of consciousness, and delirious behavior. Thirteen patients completely recovered within 1 month, but 2 patients who were subjected to mechanical ventilation had persistent neurological deficits. The initial MRI features showed isolated ovoid or extending SCC lesions with homogeneous hyperintense on diffusion weighted imaging (DWI) and decreased apparent diffusion coefficient (ADC) values. The follow-up MRI revealed that isolated SCC lesions with diffuse restriction disappeared at 10 to 32 days after the initial MRI study. Fractional anisotropy map revealed the decreased value of SCC lesion in a severe case with poor prognosis. RESLES associated with encephalitis/encephalopathy is a reversible syndrome with an excellent prognosis in most patients, while a few patients required ventilator supporting at the early stage might have severe neurological sequelae. Reversible signal changes on DWI and ADC are identified in all patients, but fractional anisotropy values can be decreased in severe patient with neurological

Neonatal encephalopathy and socioeconomic status: population-based case-control study.

PubMed

Blume, Heidi K; Loch, Christian M; Li, Christopher I

2007-07-01

To investigate the association between maternal socioeconomic status and the risk of encephalopathy in full-term newborns. Population-based case-control study. Washington State births from 1994 through 2002 recorded in the linked Washington State Birth Registry and Comprehensive Hospital Abstract Reporting System. Cases (n = 1060) were singleton full-term newborns with Comprehensive Hospital Abstract Reporting System International Classification of Diseases, Ninth Revision diagnoses of seizures, birth asphyxia, central nervous system dysfunction, or cerebral irritability. Control cases (n = 5330) were singleton full-term newborns selected from the same database. Main Exposures Socioeconomic status was defined by median income of the census tract of the mother's residence, number of years of maternal educational achievement, or maternal insurance status. Odds ratios estimating the risk of encephalopathy associated with disadvantaged socioeconomic status were calculated in 3 separate analyses using multivariate adjusted logistic regression. Newborns of mothers living in neighborhoods in which residents have a low median income were at increased risk of encephalopathy compared with newborns in neighborhoods in which residents have a median income more than 3 times the poverty level (adjusted odds ratio, 1.9; 95% confidence interval, 1.5-2.3). There was also a trend for increasing risk of encephalopathy associated with decreasing neighborhood income (P<.001). Newborns of mothers with less than 12 years of educational achievement had a higher risk of encephalopathy compared with newborns of mothers with more than 16 years of educational achievement (adjusted odds ratio, 1.7; 95% confidence interval, 1.3-2.3). Newborns of mothers receiving public insurance also had a higher risk of encephalopathy compared with newborns of mothers who have commercial insurance (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7). Disadvantaged socioeconomic status was

Chronic traumatic encephalopathy in sports: a historical and narrative review.

PubMed

Solomon, Gary

2018-01-01

My objectives are to review: 1) a brief history of sport-related concussion (SRC) and chronic traumatic encephalopathy (CTE), 2) the evolution of CTE in American professional football, 3) the data regarding SRC/CTE as they relate to depression and suicide, 4) the data on the neurocognitive effects of subconcussion/repetitive head trauma (with emphases on heading the ball in soccer and early exposure to football), 5) the evidence related to SRC and neurodegenerative diseases, 6) the published studies of CTE, 7) the NINDS neuropathological criteria for CTE, 8) public beliefs about SRC/CTE, and 9) the scientific questions regarding CTE.

Chronic traumatic encephalopathy: contributions from the Boston University Center for the Study of Traumatic Encephalopathy.

PubMed

Riley, David O; Robbins, Clifford A; Cantu, Robert C; Stern, Robert A

2015-01-01

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.

Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes.

PubMed

Tzoulis, Charalampos; Neckelmann, Gesche; Mørk, Sverre J; Engelsen, Bernt E; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A

2010-05-01

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that characteristically shows episodes of rapid neurological deterioration and the development of acute cerebral lesions. The purpose of this study was to investigate the nature, distribution and natural evolution of central nervous system lesions in polymerase gamma associated encephalopathy focusing particularly on lesions identified by magnetic resonance imaging. We compared radiological, electrophysiological and pathological findings where available to study potential mechanisms underlying the episodes of exacerbation and acute cerebral lesions. We studied a total of 112 magnetic resonance tomographies and 11 computed tomographies in 32 patients with polymerase gamma-encephalopathy, including multiple serial examinations performed during both the chronic and acute phases of the disease and, in several cases, magnetic resonance spectroscopy and serial diffusion weighted studies. Data from imaging, electroencephalography and post-mortem examination were compared in order to study the underlying disease process. Our findings show that magnetic resonance imaging in polymerase gamma-related encephalopathies has high sensitivity and can identify patterns that are specific for individual syndromes. One form of chronic polymerase gamma-encephalopathy, that is associated with the c.1399G > A and c.2243G > C mutations, is characterized by progressive cerebral and cerebellar atrophy and focal lesions of the thalamus, deep cerebellar structures and medulla oblongata. Acute encephalopathies, both infantile and later onset, show similar pictures with cortical stroke-like lesions occurring during episodes of exacerbation. These lesions can occur both

Seeing more clearly through the fog of encephalopathy.

PubMed

Kaplan, Peter W; Sutter, Raoul

2013-10-01

Patients with acute confusional states (often referred to as encephalopathy or delirium) pose diagnostic and management challenges for treating physicians. Encephalopathy is associated with a high morbidity and mortality rate, and the diagnosis rests on clinical grounds but may also be supported by the finding of electroencephalographic (EEG) evidence for diffuse cerebral dysfunction. The myriad cerebral transmitter and metabolic disruptions are generated by systemic organ system failures, principal among which are those of the liver, kidneys, lungs, heart, and endocrine system, along with the effects of exogenous toxins and medications. In most cases, several of these organ failures together contribute to the confusional state, frequently in the context of a diffuse cerebral atrophy that affects the aging brain. This special issue of the Journal of Clinical Neurophysiology is dedicated to exploring the electrophysiology of these conditions. It reviews the pathophysiology, psychiatric manifestations, clinical and imaging correlations of the many causes and types of encephalopathy. A literature review of the EEG abnormalities in the various types of encephalopathy provides an overview that ranges from paraneoplastic causes, through organ system failures, postcardiorespiratory arrest, to postoperative delirium. The issue is supplemented by tables of relevant clinical correlations, graphs, Venn diagrams, and the use of mathematical modeling used to explain how defects in the neuronal interplay might generate the EEG patterns seen in encephalopathy. We hope that this assembly will act as a springboard for further discussion and investigation into the EEG underpinnings, clinical correlations, diagnosis. and prognostication of these common and morbid disturbances of brain function.

Potentially modifiable factors contributing to sepsis-associated encephalopathy.

PubMed

Sonneville, Romain; de Montmollin, Etienne; Poujade, Julien; Garrouste-Orgeas, Maïté; Souweine, Bertrand; Darmon, Michael; Mariotte, Eric; Argaud, Laurent; Barbier, François; Goldgran-Toledano, Dany; Marcotte, Guillaume; Dumenil, Anne-Sylvie; Jamali, Samir; Lacave, Guillaume; Ruckly, Stéphane; Mourvillier, Bruno; Timsit, Jean-François

2017-08-01

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes. We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively. We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19-1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27-5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09-1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53-2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48-3.57), and S. aureus (aOR = 1.54, 95% CI 1.05-2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13-14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09-1.76). Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

Transmissible Spongiform Encephalopathies (Prion Diseases)

MedlinePlus

... have resulted from human consumption of beef from cattle with a TSE disease called bovine spongiform encephalopathy (BSE), also known as "mad cow disease." Other TSEs found in animals include scrapie, ...

Newborns Referred for Therapeutic Hypothermia: Association between Initial Degree of Encephalopathy and Severity of Brain Injury (What About the Newborns with Mild Encephalopathy on Admission?).

PubMed

Gagne-Loranger, Maude; Sheppard, Megan; Ali, Nabeel; Saint-Martin, Christine; Wintermark, Pia

2016-01-01

The aim of this article was to describe the severity of brain injury and/or mortality in a cohort of newborns referred for therapeutic hypothermia, in relation to the degree of encephalopathy on admission, and to especially look at the ones with initial mild encephalopathy. Term newborns with perinatal depression referred to our neonatal intensive care unit for possible hypothermia treatment from 2008 to 2012 were enrolled prospectively. The modified Sarnat score on admission was correlated with severity of brain injury on brain imaging and/or autopsy. A total of 215 newborns were referred for possible cooling. Sixty percent (128/215) were cooled. Most of the not-cooled newborns with an available brain magnetic resonance imaging (85% = 50/59) had an initial mild encephalopathy, and 40% (20/50) developed brain injury. Some cooled newborns had an initial mild encephalopathy (12% = 13/108); only 31% (4/13) developed brain injury. Our results demonstrated that several newborns with an initial mild encephalopathy developed subsequent brain injury, especially when they were not cooled. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

PubMed

Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

2015-07-01

Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates. Copyright © 2015 Elsevier Inc. All rights reserved.

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.

PubMed

Bailey, Julia N; Patterson, Christopher; de Nijs, Laurence; Durón, Reyna M; Nguyen, Viet-Huong; Tanaka, Miyabi; Medina, Marco T; Jara-Prado, Aurelio; Martínez-Juárez, Iris E; Ochoa, Adriana; Molina, Yolli; Suzuki, Toshimitsu; Alonso, María E; Wight, Jenny E; Lin, Yu-Chen; Guilhoto, Laura; Targas Yacubian, Elza Marcia; Machado-Salas, Jesús; Daga, Andrea; Yamakawa, Kazuhiro; Grisar, Thierry M; Lakaye, Bernard; Delgado-Escueta, Antonio V

2017-02-01

EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case-control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1 -/- KO mice recapitulate CTC convulsions and "microdysgenesis" neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. Nine variants were classified as "pathogenic," 14 as "likely pathogenic," 9 as "benign," and 2 as "likely benign." Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non-ion channel microtubule-associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and "microdysgenesis" neuropathology of JME.Genet Med 19 2, 144-156.

Wernicke’s encephalopathy associated with liver abscess.

PubMed

Verma, Rajesh; Garg, Vipul

2017-07-31

Wernicke's encephalopathy is a rare neurological disorder caused by thiamine deficiency, characterised by ocular motor dysfunction, ataxia and impairment in consciousness. It predominantly affects brain regions with a high metabolic rate such as mammillary bodies, medial thalamic nuclei, the tectal region and the cerebellum. Although chronic alcoholism is the most common cause of Wernicke's encephalopathy, various other conditions not related to alcohol consumption such as bariatric surgery, acute pancreatitis, hyperemesis gravidarum, prolonged fasting and gastrointestinal surgery have been implicated in its aetiology. We report the case of a patient who underwent surgery for liver abscess and subsequently developed Wernicke's encephalopathy; he showed a positive response to thiamine supplementation. This is the first report describing liver abscess as the cause of Wernicke's encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SCN8A encephalopathy: Research progress and prospects

PubMed Central

Meisler, Miriam H.; Helman, Guy; Hammer, Michael F.; Fureman, Brandy E.; Gaillard, William D.; Goldin, Alan L.; Hirose, Shinichi; Ishii, Atsushi; Kroner, Barbara L.; Lossin, Christoph; Mefford, Heather C.; Parent, Jack M.; Patel, Manoj; Schreiber, John; Stewart, Randall; Whittemore, Vicky; Wilcox, Karen; Wagnon, Jacy L; Pearl, Phillip L.; Vanderver, Adeline; Scheffer, Ingrid E.

2017-01-01

On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. PMID:27270488

The posterior reversible encephalopathy syndrome.

PubMed

Sanjay, K Mandal; Partha, P Chakraborty

2008-09-01

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.

Two Novel Variants Affecting CDKL5 Transcript Associated with Epileptic Encephalopathy.

PubMed

Neupauerová, Jana; Štěrbová, Katalin; Vlčková, Markéta; Sebroňová, Věra; Maříková, Tat'ána; Krůtová, Marcela; David, Staněk; Kršek, Pavel; Žaliová, Markéta; Seeman, Pavel; Laššuthová, Petra

2017-10-01

Variants in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been reported as being etiologically associated with early infantile epileptic encephalopathy type 2 (EIEE2). We report on two patients, a boy and a girl, with EIEE2 that present with early onset epilepsy, hypotonia, severe intellectual disability, and poor eye contact. Massively parallel sequencing (MPS) of a custom-designed gene panel for epilepsy and epileptic encephalopathy containing 112 epilepsy-related genes was performed. Sanger sequencing was used to confirm the novel variants. For confirmation of the functional consequence of an intronic CDKL5 variant in patient 2, an RNA study was done. DNA sequencing revealed de novo variants in CDKL5, a c.2578C>T (p. Gln860*) present in a hemizygous state in a 3-year-old boy, and a potential splice site variant c.463+5G>A in heterozygous state in a 5-year-old girl. Multiple in silico splicing algorithms predicted a highly reduced splice site score for c.463+5G>A. A subsequent mRNA study confirmed an aberrant shorter transcript lacking exon 7. Our data confirmed that variants in the CDKL5 are associated with EIEE2. There is credible evidence that the novel identified variants are pathogenic and, therefore, are likely the cause of the disease in the presented patients. In one of the patients a stop codon variant is predicted to produce a truncated protein, and in the other patient an intronic variant results in aberrant splicing.

Expression and role of neuroglobin in rats with sepsis-associated encephalopathy.

PubMed

Zhang, Li-Na; Ai, Yu-Hang; Gong, Hua; Guo, Qu-Lian; Huang, Li; Liu, Zhi-Yong; Yao, Bo

2014-01-01

To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. Randomized laboratory animal study. Research university animal laboratory. Two hundred and forty adult male Sprague-Dawley rats. Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on

Brainstem evoked response audiometry: an investigatory tool in detecting hepatic encephalopathy in decompensated chronic liver disease.

PubMed

Kabali, Balasubramanian; Velayutham, Gowri; Kapali, Suresh Chander

2014-01-01

It is estimated that globally there is a marked increase in liver disease with reports of rising morbidity and mortality, particularly in younger age groups. Brainstem auditory evoked potential (BAEP) was recorded in 60 decompensated chronic liver disease (DCLD) subjects who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. DCLD subjects were divided into two inter groups based on presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade- I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Absolute and interpeak wave latencies were measured. Results were analysed by student independent t- test using SPSS software 11 version. Statistical significance was tested using P value. From the present study it can be concluded that the central nervous system is involved in liver cirrhosis evidenced by an abnormal BAEP latencies parameters. This shows that there may be progressive demyelination occurring along with axonal loss or dysfunction in liver cirrhosis HE. This study suggests that periodic evaluation of cirrhotic individuals to such test will help in monitoring the progress of encephalopathy. The prime goal of this study is early diagnosis and initiation of treatment before the onset of coma can reduce the fatality rate.

Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy.

PubMed

Shapiro, Kevin A; Kim, Hosung; Mandelli, Maria Luisa; Rogers, Elizabeth E; Gano, Dawn; Ferriero, Donna M; Barkovich, A James; Gorno-Tempini, Maria Luisa; Glass, Hannah C; Xu, Duan

2017-01-01

Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE). However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM) to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III) at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes.

Seizure outcome in 175 patients with juvenile myoclonic epilepsy--a long-term observational study.

PubMed

Höfler, Julia; Unterberger, Iris; Dobesberger, Judith; Kuchukhidze, Giorgi; Walser, Gerald; Trinka, Eugen

2014-12-01

Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. We retrospectively studied 242 patients with JME at the Department of Neurology, Medical University Innsbruck, Austria (1975-2006). We analyzed age at seizure onset, age at last follow up, seizure types, photosensitivity, seizure outcome and neuroimaging findings; inclusion criterion was a medical treatment period of >2 years; exclusion criteria were traumatic or infectious brain injury before the onset of JME and/or gross structural pathology on neuroimaging. We identified 175 patients (111 women) with a median age at seizure onset of 15 years, (range 3-46) and a median age at follow-up (FU) of 38 years (range 14-87; median FU 8 years, range 2-38). Fourteen percent showed (24/175) photosensitivity on routine EEG. Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for >1 year, and 53% (94/175) for >2 years, including 16 patients (9%) without AEDs. Thirty-one percent (54/175) were seizure-free between 2 and 5 years, 15% (26/175) between 6 and 10, and 8% (14/175) >10 years; 38% (66/175) were not seizure-free. Not seizure-free patients had more often MS, AS and GTCS within the first year of epilepsy than those who were seizure-free at last FU (11% vs. 3%, Chi(2)=4.679, df=1, p=0.043). Seizure-free patients had more often MS and GTCS as last seizure types in the year before becoming seizure-free (37% vs. 15%, p=0.003), whereas in not seizure-free group MS only and GTCS only persisted. JME does not always need lifelong treatment, as a substantial minority of patients remain seizure-free without AEDs. AS, MS and GTCS at onset of the disease are indicators of poor long-term seizure control. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Juvenile myoclonic epilepsy presenting as a new daily persistent-like headache.

PubMed

Rozen, Todd D

2011-12-01

New daily persistent headache (NDPH) is a recognized subtype of chronic daily headache with a unique presentation of a daily headache from onset typically in individuals with minimal or no prior headache history. Various secondary mimics of NDPH have now been documented but at present there has been no association made between primary epilepsy syndromes and new daily persistent-like headaches. A case patient is presented who developed a daily continuous headache from onset who 3 months after headache initiation had her first generalized tonic-clonic seizure. Further investigation into her history and her specific EEG pattern suggested a diagnosis of juvenile myoclonic epilepsy (JME). Her NDPH and seizures ceased with epilepsy treatment. Clinically relevant was that the headache was the primary persistent clinical symptom of her JME before the onset of generalized tonic-clonic seizures. The current case report adds another possible secondary cause of new daily persistent-like headaches to the medical literature and suggests another association between primary epilepsy syndromes and distinct headache syndromes.

Bronchiolitis-associated encephalopathy in critically-ill infants: an underestimated complication?

PubMed

Antonucci, Roberto; Chiappe, Stefano; Porcella, Annalisa; Rosatelli, Daniela; Fanos, Vassilios

2010-05-01

To investigate the bronchiolitis-associated encephalopathy in critically ill infants. The records of infants with severe bronchiolitis admitted to our intensive care unit between 1991 and 2003 were reviewed. Subjects with underlying neurological disorders were excluded. Encephalopathy was defined as occurrence of seizures or at least two nonconvulsive neurologic manifestations. A semistructured telephone interview investigated long-term neurodevelopmental outcome. Twenty-one infants (11 newborns) were enrolled. All patients required oxygen supplementation and 14 required mechanical ventilation. Encephalopathy occurred in 10 infants, six of whom developed seizures. Encephalopathic infants frequently (six of nine) showed transient EEG abnormalities, and occasionally (one of nine) cranial ultrasound abnormalities. A positive respiratory syncytial virus test was found in five of nine encephalopathic infants. One encephalopathic patient died, while 20 infants clinically normalised before discharge and showed a good neurodevelopmental outcome. Acute encephalopathy was frequently observed in our patients with severe bronchiolitis. Long-term prognosis of encephalopathic infants was good.

Therapeutic benefits of ACTH and levetiracetam in STXBP1 encephalopathy with a de novo mutation: A case report and literature review.

PubMed

Liu, Shunli; Wang, Liyuan; Cai, Xiao Tang; Zhou, Hui; Yu, Dan; Wang, Zhiling

2018-05-01

The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation. Early-onset epileptic encephalopathy with STXBP1 mutation. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.

Stimulus induced bursts in severe postanoxic encephalopathy.

PubMed

Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M

2016-11-01

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.

SCN8A encephalopathy: Research progress and prospects.

PubMed

Meisler, Miriam H; Helman, Guy; Hammer, Michael F; Fureman, Brandy E; Gaillard, William D; Goldin, Alan L; Hirose, Shinichi; Ishii, Atsushi; Kroner, Barbara L; Lossin, Christoph; Mefford, Heather C; Parent, Jack M; Patel, Manoj; Schreiber, John; Stewart, Randall; Whittemore, Vicky; Wilcox, Karen; Wagnon, Jacy L; Pearl, Phillip L; Vanderver, Adeline; Scheffer, Ingrid E

2016-07-01

On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Valproic acid induced hyperammonaemic encephalopathy.

PubMed

Amanat, Saima; Shahbaz, Naila; Hassan, Yasmin

2013-01-01

To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excell 2007 was used for statistical analysis. Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n = 8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition.

Advanced neuroimaging techniques for the term newborn with encephalopathy.

PubMed

Chau, Vann; Poskitt, Kenneth John; Miller, Steven Paul

2009-03-01

Neonatal encephalopathy is associated with a high risk of morbidity and mortality in the neonatal period and of long-term neurodevelopmental disability in survivors. Advanced magnetic resonance techniques now play a major role in the clinical care of newborns with encephalopathy and in research addressing this important condition. From conventional magnetic resonance imaging, typical patterns of injury have been defined in neonatal encephalopathy. When applied in contemporary cohorts of newborns with encephalopathy, the patterns of brain injury on magnetic resonance imaging distinguish risk factors, clinical presentation, and risk of abnormal outcome. Advanced magnetic resonance techniques such as magnetic resonance spectroscopy, diffusion-weighted imaging, and diffusion tensor imaging provide novel perspectives on neonatal brain metabolism, microstructure, and connectivity. With the application of these imaging tools, it is increasingly apparent that brain injury commonly occurs at or near the time of birth and evolves over the first weeks of life. These observations have complemented findings from trials of emerging strategies of brain protection, such as hypothermia. Application of these advanced magnetic resonance techniques may enable the earliest possible identification of newborns at risk of neurodevelopmental impairment, thereby ensuring appropriate follow-up with rehabilitation and psychoeducational resources.

[Clinical features and magnetic resonance imaging evaluation of encephalopathy in high-risk late preterm infants].

PubMed

Zhu, Yan; Zhang, Ke; Hu, Lan; Xiao, Mi-Li; Li, Zhi-Hua; Chen, Chao

2017-05-01

To investigate the risk factors, clinical features, and magnetic resonance imaging (MRI) changes of encephalopathy in high-risk late preterm infants. Head MRI scan was performed for late preterm infants with high-risk factors for brain injury who were hospitalized between January 2009 and December 2014. The risk factors, clinical features, and head MRI features of encephalopathy in late preterm infants were analyzed. A total of 1 007 late preterm infants underwent MRI scan, among whom 313 (31.1%) had imaging features in accordance with the features of encephalopathy of prematurity. Of all infants, 76.7% had white matter damage. There was no association between the development of encephalopathy and gestational age in late preterm infants, but the detection rate of encephalopathy gradually increased with the increasing birth weight (P<0.05). The logistic regression analysis showed that a history of resuscitation was an independent risk factor for encephalopathy of prematurity (P<0.01). Encephalopathy of prematurity is commonly seen in high-risk late preterm infants, especially white matter damage. A history of resuscitation is an independent risk factor for encephalopathy in late preterm infants.

Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.

PubMed

Silveira, Rita C; Procianoy, Renato S

2015-01-01

Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis?

PubMed

Lorenzoni, Paulo José; Werneck, Lineu Cesar; Kay, Cláudia Suemi Kamoi; Silvado, Carlos Eduardo Soares; Scola, Rosana Herminia

2015-11-01

Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological) and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR) gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF) and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments.

Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy

PubMed Central

Tam, Emily W.Y.; Haeusslein, Laurel A.; Bonifacio, Sonia L.; Glass, Hannah C.; Rogers, Elizabeth E.; Jeremy, Rita J.; Barkovich, A. James; Ferriero, Donna M.

2012-01-01

Objective To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. Study design A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain MRI studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at one year of age. Results Hypoglycemia (glucose <46mg/dL) in the first 24 hours after birth was detected in 16% of the cohort. Adjusting for potential confounders of early perinatal distress and need for resuscitation, neonatal hypoglycemia was associated with a 3.72-fold increased odds of corticospinal tract injury (P=0.047). Hypoglycemia was also associated with 4.82-fold increased odds of one-point worsened neuromotor score (P=0.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=0.015). Conclusion Neonatal hypoglycemia is associated with additional risks in the setting of neonatal encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. PMID:22306045

Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy.

PubMed

Tam, Emily W Y; Haeusslein, Laurel A; Bonifacio, Sonia L; Glass, Hannah C; Rogers, Elizabeth E; Jeremy, Rita J; Barkovich, A James; Ferriero, Donna M

2012-07-01

To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. Hypoglycemia (glucose <46 mg/dL) in the first 24 hours after birth was detected in 16% of the cohort. Adjusting for potential confounders of early perinatal distress and need for resuscitation, neonatal hypoglycemia was associated with a 3.72-fold increased odds of corticospinal tract injury (P=.047). Hypoglycemia was also associated with 4.82-fold increased odds of 1-point worsened neuromotor score (P=.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=.015). Neonatal hypoglycemia is associated with additional risks in the setting of neonatal encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. Copyright © 2012 Mosby, Inc. All rights reserved.

Endocannabinoids in liver disease and hepatic encephalopathy.

PubMed

Magen, Iddo; Avraham, Yosefa; Berry, Elliot; Mechoulam, Raphael

2008-01-01

Chronic liver disease results from a variety of causes such as hepatitis virus infections, autoimmune processes and alcohol consumption. Its complications include fat deposition, hemodynamic changes and fibrosis. Clinically there may be progression to portal-hypertension and porto-systemic encephalopathy. Pioneering research from the laboratory of Kunos at NIH has stressed the importance of endocannabinoids (ECs) as mediators of some of the pathological processes in chronic liver disease. The present review summarizes the literature on the association between ECs and liver disease, as well as the therapeutic potential of ECs and exogenous cannabinoids in liver disease with emphasis on hepatic encephalopathy.

Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

PubMed

Nukui, Megumi; Kawawaki, Hisashi; Inoue, Takeshi; Kuki, Ichiro; Okazaki, Shin; Amo, Kiyoko; Togawa, Masao; Ishikawa, Junichi; Rinka, Hiroshi; Shiomi, Masashi

2018-06-07

Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders.

PubMed

Ohba, Chihiro; Shiina, Masaaki; Tohyama, Jun; Haginoya, Kazuhiro; Lerman-Sagie, Tally; Okamoto, Nobuhiko; Blumkin, Lubov; Lev, Dorit; Mukaida, Souichi; Nozaki, Fumihito; Uematsu, Mitsugu; Onuma, Akira; Kodera, Hirofumi; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Miyake, Noriko; Tanaka, Fumiaki; Kato, Mitsuhiro; Ogata, Kazuhiro; Saitsu, Hirotomo; Matsumoto, Naomichi

2015-06-01

Recently, de novo mutations in GRIN1 have been identified in patients with nonsyndromic intellectual disability and epileptic encephalopathy. Whole exome sequencing (WES) analysis of patients with genetically unsolved epileptic encephalopathies identified four patients with GRIN1 mutations, allowing us to investigate the phenotypic spectrum of GRIN1 mutations. Eighty-eight patients with unclassified early onset epileptic encephalopathies (EOEEs) with an age of onset <1 year were analyzed by WES. The effect of mutations on N-methyl-D-aspartate (NMDA) receptors was examined by mapping altered amino acids onto three-dimensional models. We identified four de novo missense GRIN1 mutations in 4 of 88 patients with unclassified EOEEs. In these four patients, initial symptoms appeared within 3 months of birth, including hyperkinetic movements in two patients (2/4, 50%), and seizures in two patients (2/4, 50%). Involuntary movements, severe developmental delay, and intellectual disability were recognized in all four patients. In addition, abnormal eye movements resembling oculogyric crises and stereotypic hand movements were observed in two and three patients, respectively. All the four patients exhibited only nonspecific focal and diffuse epileptiform abnormality, and never showed suppression-burst or hypsarrhythmia during infancy. A de novo mosaic mutation (c.1923G>A) with a mutant allele frequency of 16% (in DNA of blood leukocytes) was detected in one patient. Three mutations were located in the transmembrane domain (3/4, 75%), and one in the extracellular loop near transmembrane helix 1. All the mutations were predicted to impair the function of the NMDA receptor. Clinical features of de novo GRIN1 mutations include infantile involuntary movements, seizures, and hand stereotypies, suggesting that GRIN1 mutations cause encephalopathy resulting in seizures and movement disorders. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

[Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

PubMed

Song, Min-ning; Song, Yu-na; Chen, Fu; Luo, Mei-lan

2007-01-01

To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(P<0.05 or P<0.01). The clinical manifestations, liver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both P<0.01], while the value of NA decreased in the group of CLF encephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,P<0.05]. The levels of 5-HT are elevated in the groups of ALF encephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

Chronic traumatic encephalopathy.

PubMed

Omalu, Bennet

2014-01-01

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. © 2014 S. Karger AG, Basel.

Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

PubMed

Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

2017-04-01

Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p < 0.0001). Cirrhotic patients with ACLF have decreased CSF-SG as compared to cirrhotic patients without ACLF (-0.2 %, p = 0.0030) that remained higher than in healthy controls. The presence of hepatic encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to

Models for discovery of targeted therapy in genetic epileptic encephalopathies.

PubMed

Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

Fifty years of brain imaging in neonatal encephalopathy following perinatal asphyxia.

PubMed

Groenendaal, Floris; de Vries, Linda S

2017-01-01

In the past brain imaging of term infants with hypoxic-ischemic encephalopathy (HIE) was performed with cranial ultrasound (cUS) and computed tomography (CT). Both techniques have several disadvantages sensitivity and specificity is limited compared with magnetic resonance imaging (MRI) and CT makes use of radiation. At present MRI including diffusion weighted MRI during the first week of life, has become the method of choice for imaging infants with HIE. In addition to imaging, blood vessels and blood flow can be visualized using MR angiography, MR venography, and arterial spin labeling. Since the use of these techniques additional lesions in infants with HIE, such as arterial ischemic stroke, sinovenous thrombosis, and subdural hemorrhages can be diagnosed, and the incidence appears to be higher than shown previously. Phosphorus magnetic resonance spectroscopy (MRS) has led to the concept of secondary energy failure in infants with HIE, but has not been widely used. Proton MRS of the basal ganglia and thalamus is one of the best predictors of neurodevelopmental outcome. cUS should still be used for screening infants admitted to a NICU with neonatal encephalopathy. In the future magnetic resonance techniques will be increasingly used as early biomarkers of neurodevelopmental outcome in trials of neuroprotective strategies.

Head stereotypies in STXBP1 encephalopathy.

PubMed

Kim, Young Ok; Korff, Christian M; Villaluz, Mel Michel G; Suls, Arvid; Weckhuysen, Sarah; De Jonghe, Peter; Scheffer, Ingrid E

2013-08-01

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.

Acute Necrotizing Encephalopathy of Childhood (ANEC): A Case Report

PubMed Central

HASSANZADEH RAD, Afagh; AMINZADEH, Vahid

2017-01-01

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

Can the tyrosine kinase inhibitors trigger metabolic encephalopathy in cirrhotic patients?

PubMed

Brandi, Giovanni; de Rosa, Francesco; Calzà, Laura; Girolamo, Stefania Di; Tufoni, Manuel; Ricci, Carmen Serena; Cirignotta, Fabio; Caraceni, Paolo; Biasco, Guido

2013-03-01

Sorafenib is the standard treatment of advanced hepatocarcinoma (HCC) in cirrhotic patients with preserved liver function. It shares many adverse effects with other tyrosine-kinase (TK) inhibitors and antiangiogenic drugs. TK inhibitors could have a direct toxicity on CNS, both by interfering with TK-related pathways and by inhibiting angiogenesis. The aim of this study was to investigate whether sorafenib administration can be associated to metabolic encephalopathy in patients with cirrhosis. We retrospectively reviewed medical records of all cirrhotic patients treated with sorafenib for HCC afferent at our Department from January 2009 to December 2011. Among 62 patients, we identified 10 patients with clinically significant cognitive impairment. Seven of these were clearly diagnosed with overt hepatic encephalopathy (HE), one with brain metastases and two with drug-related toxic-metabolic encephalopathy. These last two cases were characterized by severe cognitive impairment, mood alteration and memory deficit. Clinical exam, blood tests and brain CT excluded organic causes of encephalopathy and precipitating factors of HE. Sorafenib discontinuation was associated with complete reversal of the syndrome, which recurred on drug re-administration in one case. Our study suggests that sorafenib may be a precipitating factor of metabolic encephalopathy in cirrhotic patients with advanced HCC. This neurological syndrome appears to be not responsive to the conventional treatment for HE, but it is fully reversible by drug discontinuation. It can be speculated that the potential direct neuronal action of sorafenib may represent a trigger for the onset of metabolic encephalopathy in a subset of cirrhotic patients. © 2012 John Wiley & Sons A/S.

Localized Cerebral Energy Failure in DNA Polymerase Gamma-Associated Encephalopathy Syndromes

ERIC Educational Resources Information Center

Tzoulis, Charalampos; Neckelmann, Gesche; Mork, Sverre J.; Engelsen, Bernt E.; Viscomi, Carlo; Moen, Gunnar; Ersland, Lars; Zeviani, Massimo; Bindoff, Laurence A.

2010-01-01

Mutations in the catalytic subunit of the mitochondrial DNA-polymerase gamma cause a wide spectrum of clinical disease ranging from infantile hepato-encephalopathy to juvenile/adult-onset spinocerebellar ataxia and late onset progressive external ophthalmoplegia. Several of these syndromes are associated with an encephalopathy that…

Communication Challenges in Neonatal Encephalopathy.

PubMed

Lemmon, Monica E; Donohue, Pamela K; Parkinson, Charlamaine; Northington, Frances J; Boss, Renee D

2016-09-01

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.

Neonatal encephalopathy and the association to asphyxia in labor.

PubMed

Jonsson, Maria; Ågren, Johan; Nordén-Lindeberg, Solveig; Ohlin, Andreas; Hanson, Ulf

2014-12-01

In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome. In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, <7.00; base deficit, ≥12 mmol/L). Cases with normal admission CTG patterns and asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery. Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively). Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

Long term results of balloon-occluded retrograde transvenous obliteration for portosystemic shunt encephalopathy in patients with liver cirrhosis and portal hypertension.

PubMed

Inoue, Hiroto; Emori, Keigo; Toyonaga, Atsushi; Oho, Kazuhiko; Kumamoto, Masafumi; Haruta, Tsuyoshi; Mitsuyama, Keiichi; Tsuruta, Osamu; Sata, Michio

2014-01-01

This study examined 19 patients with portosystemic shunt encephalopathy caused by a splenorenal shunt (SRS), which was treated with balloon-occluded retrograde transvenous obliteration (B-RTO). Long-term treatment outcomes were evaluated based on hepatic functional reserve and vital prognosis. Encephalopathy improved in all patients after shunt embolization and closure. Albumin, serum ammonia, and the Child-Pugh score, a measure of liver function, were significantly improved 3 years after B-RTO, and exacerbation of damage to liver function was avoided (p<0.01). During the follow-up period, three patients died from liver failure and two patients from hepatocellular carcinoma. Patients had a poor prognosis if their albumin levels were less than 2.8 mg / dL before B-RTO (p<0.05). Encephalopathy patients had complete response to B-RTO, but long-term prognosis was affected by hepatic functional reserve before B-RTO and by concurrent hepatocellular carcinoma. The results of this study suggest that in patients with SRS, it is important to perform B-RTO at an early stage when the hepatic functional reserve is still satisfactory.

Subacute sclerosing panencephalitis.

PubMed

Garg, Ravindra Kumar

2008-12-01

Subacute sclerosing panencephalitis (SSPE) is a subacute encephalopathy of childhood and young adolescence. Infrequently, SSPE can occur in adults and pregnant women. It is caused by an aberrant measles virus, known as the SSPE virus. SSPE virus differs from wild-type measles viruses in the form of several mutations affecting the viral genome. The matrix gene is most commonly affected by these mutations. The characteristic clinical manifestations of SSPE include behavioral changes, cognitive decline, myoclonic jerks, seizures, abnormalities in vision, bilateral pyramidal signs and coma. Ocular changes may occur in up to 50% of patients. The most characteristic ophthalmological lesion is necrotizing retinitis. Cortical blindness can be the early feature of SSPE. The diagnosis of SSPE is often difficult in the early stages. In a typical case diagnosis is based on clinical, electroencephalographic, and cerebrospinal fluid findings. At present, there is no effective treatment to completely cure SSPE. Oral isoprinosine and intrathecal or intraventricular alpha-interferon may prolong survival to some extent. Immunization against measles is currently the most effective strategy against SSPE.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes

PubMed Central

Jenster, Meike; Bonifacio, Sonia L.; Ruel, Theodore; Rogers, Elizabeth E.; Tam, Emily W.; Partridge, John Colin; Barkovich, A. James; Ferriero, Donna M.; Glass, Hannah C.

2014-01-01

Background Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. Methods Cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern and severity of injury on neonatal MRI, as well as neurodevelopment at 30 months (neuromotor exam, or Bayley Scales of Infant Development II MDI <70 or Bayley III cognitive score <85). Results Chorioamnionitis was associated with lower risk of moderate-severe brain injury (adjusted OR 0.3; 95% CI 0.1–0.7, P=0.004), and adverse cognitive outcome in children when compared to no chorioamnionitis. Children with signs of neonatal sepsis were more likely to exhibit watershed predominant injury than those without (P=0.007). Conclusions Among neonates with encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns. PMID:24713817

Acute Infantile Encephalopathy Predominantly Affecting The Frontal Lobes (AIEF).

PubMed

Raha, Sarbani; Udani, Vrajesh

2012-12-01

Acute Infantile Encephalopathy Predominantly Affecting the Frontal Lobes (AIEF) is a relatively recent described entity. This article includes case reports of two patients who had bifrontal involvement during acute febrile encephalopathy. Case 1 describes a 1-y-old boy who presented with hyperpyrexia and dialeptic seizures. Imaging revealed significant bilateral frontal lobe involvement while serology proved presence of Influenza B infection. Over a period of one wk, he recovered with significant cognitive decline and perseveratory behavior. Another 6-y-old boy presented with language and behavioral problems suggestive of frontal dysfunction after recovering from prolonged impairment of consciousness following a convulsive status epilepticus. Bilateral superior frontal lesions with gyral swelling was evident on neuroimaging. These cases are among the very few cases of AIEF described in recent literature and the article also reviews this unique subtype of acute encephalopathy.

Probiotics for people with hepatic encephalopathy.

PubMed

Dalal, Rohan; McGee, Richard G; Riordan, Stephen M; Webster, Angela C

2017-02-23

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

Risk factors for neonatal encephalopathy in Kathmandu, Nepal, a developing country: unmatched case-control study

PubMed Central

Ellis, Matthew; Manandhar, Nilu; Manandhar, Dharma S; Costello, Anthony M de L

2000-01-01

Objective To determine the risk factors for neonatal encephalopathy among term infants in a developing country. Design Unmatched case-control study. Setting Principal maternity hospital of Kathmandu, Nepal. Subjects All 131 infants with neonatal encephalopathy from a population of 21 609 infants born over an 18 month period, and 635 unmatched infants systematically recruited over 12 months. Main outcome measures Adjusted odds ratio estimates for antepartum and intrapartum risk factors. Results The prevalence of neonatal encephalopathy was 6.1 per 1000 live births of which 63% were infants with moderate or severe encephalopathy. The risk of death from neonatal encephalopathy was 31%. The risk of neonatal encephalopathy increased with increasing maternal age and decreasing maternal height. Antepartum risk factors included primiparity (odds ratio 2.0) and non-attendance for antenatal care (2.1). Multiple births were at greatly increased risk (22). Intrapartum risk factors included non-cephalic presentation (3.4), prolonged rupture of membranes (3.8), and various other complications. Particulate meconium was strongly associated with encephalopathy (18). Induction of labour with oxytocin was associated with encephalopathy in 12 of 41 deliveries (5.7). Overall, 78 affected infants (60%) compared with 36 controls (6%) either had evidence of intrapartum compromise or were born after an intrapartum difficulty likely to result in fetal compromise. A concentration of maternal haemoglobin of less than 8.0 g/dl in the puerperium was significantly associated with encephalopathy (2.5) as was a maternal thyroid stimulating hormone concentration greater than 5 mIU/l (2.1). Conclusions Intrapartum risk factors remain important for neonatal encephalopathy in developing countries. There is some evidence of a protective effect from antenatal care. The use of oxytocin in low income countries where intrapartum monitoring is suboptimal presents a major risk to the fetus. More work is

Epileptic encephalopathy in children with risk factors for brain damage.

PubMed

Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J; Barrera-Reséndiz, Jesús E; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

2012-01-01

In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy.

[Neuroprotection with hypothermia in the newborn with hypoxic-ischaemic encephalopathy. Standard guidelines for its clinical application].

PubMed

Blanco, D; García-Alix, A; Valverde, E; Tenorio, V; Vento, M; Cabañas, F

2011-11-01

Standardisation of hypothermia as a treatment for perinatal hypoxic-ischaemic encephalopathy is supported by current scientific evidence. The following document was prepared by the authors on request of the Spanish Society of Neonatology and is intended to be a guide for the proper implementation of this therapy. We discuss the difficulties that may arise when moving from the strict framework of clinical trials to clinical daily care: early recognition of clinical encephalopathy, inclusion and exclusion criteria, hypothermia during transport, type of hypothermia (selective head or systemic cooling) and side effects of therapy. The availability of hypothermia therapy has changed the prognosis of children with hypoxic-ischaemic encephalopathy and our choices of therapeutic support. In this sense, it is especially important to be aware of the changes in the predictive value of the neurological examination and the electroencephalographic recording in cooled infants. In order to improve neuroprotection with hypothermia we need earlier recognition of to recognise earlier the infants that may benefit from cooling. Biomarkers of brain injury could help us in the selection of these patients. Every single infant treated with hypothermia must be included in a follow up program in order to assess neurodevelopmental outcome. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Covert hepatic encephalopathy leads to distinct alterations in the emotional state, independently of MELD-Score.

PubMed

Greinert, Robin; Ripoll, Cristina; Zipprich, Alexander

2018-05-01

 Covert hepatic encephalopathy impairs many aspects of quality of life, although its impact on the emotional state has not been evaluated. This study aims to evaluate the impact of covert hepatic encephalopathy on the emotional state and which factors are associated with changes in the emotional state in patients with cirrhosis.  This single-center study included all patients with cirrhosis who underwent the portosystemic encephalopathy syndrome (PSE) test, critical flicker frequency, and emotional state assessment with the Eigenschaftswörterliste 60-S in 2011. Covert hepatic encephalopathy was defined by abnormal PSE. Parametric and non-parametric tests were used according to variable distribution.  One hundred seventeen patients with cirrhosis were included (median age: 59 [interquartile range: 48 - 67], 32 % female, 74 % alcohol-associated). Seventy patients had covert hepatic encephalopathy (60 %) with a higher MELD (16 [interquartile range: 13 - 21], p = 0.001) and a higher Child-Pugh score (p = 0.003) compared to patients without encephalopathy. Patients with covert encephalopathy felt reduced mental activity (p = 0.004), lower general well-being (p = 0.001), and reduced extraversion (p = 0.021). The scores in the negative domains such as general lethargy (p = 0.031) and anxiousness/depressiveness (p = 0.033) were higher in patients with covert hepatic encephalopathy. There was no correlation between MELD and the emotional state. Patients with 2 pathological tests (critical flicker frequency and PSE) showed the most distinct alterations in the emotional state in the group of patients with covert hepatic encephalopathy.  Patients with covert hepatic encephalopathy have an alteration of the emotional state, which is more marked in patients with 2 pathological tests. Interestingly, MELD had no impact on the emotional state. © Georg Thieme Verlag KG Stuttgart · New York.

Brain gamma-aminobutyric acid deficiency in dialysis encephalopathy.

PubMed

Sweeney, V P; Perry, T L; Price, J D; Reeve, C E; Godolphin, W J; Kish, S J

1985-02-01

We measured levels of gamma-aminobutyric acid (GABA) in the CSF and in the autopsied brain of patients with dialysis encephalopathy. GABA concentrations were low in the CSF of three of five living patients. Mean GABA content was reduced by 30 to 50% in five brain regions (frontal, occipital, and cerebellar cortex, caudate nucleus, and medial dorsal thalamus) in five fatal cases. GABA content was normal in brain regions where GABA is characteristically reduced in Huntington's disease. Choline acetyltransferase activity was diminished (by 25 to 35%) in cerebral cortex of the dialysis encephalopathy patients.

Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.

PubMed

Ehm, Gwanhee; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.

Management of Hepatic Encephalopathy

PubMed Central

Wright, G.; Chattree, A.; Jalan, R.

2011-01-01

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

Localization of a locus for juvenile myoclonic epilepsy on chromosome 6p11-21.2 and evidence for genetic heterogeneity

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

Liu, A.W.; Delgado-Escueta, A.V.; Alonso, V.M.E.

1994-09-01

Juvenile myoclonic epilepsy (JME) is a common form of primary idiopathic generalized epilepsy characterized by myoclonias, tonic-clonic or clonic tonic-clonic convulsions and absences. Ictal electroencephalograms (EEGs) show high amplitude multispikes folowed by slow waves and interictal EEGs manifest 3.5-6 Hz diffuse multispike wave complexes. JME affected about 7-10% of patients with epilepsies and its onset peaks between 13-15 years of age. We recently mapped a JME locus on chromosome 6p21.1-6p11 by linkage analysis of one relatively large JME family from Los Angeles and Belize. Assuming autosomal dominant inheritance with 70% penetrance, pairwise analyses tightly linked JME to D6S257 (Z =more » 3.67), D6S428 (Z = 3.08) and D6S272 (Z = 3.56) at {theta} = 0, m = f. Recombination and multipoints linkage analysis also suggested a locus is between markers D6S257 and D6S272. We then screened three relatively larger Mexican JME pedigrees with D6S257, D6S272, D6S282, TNF, D6S276, D6S273, D6S105 and F13A1 on chromosome 6p. Assuming autosomal dominant inheritance with incomplete penetrance, linkage to chromosome 6p DNA markers are excluded. Our findings underline the genetic heterogeneity of juvenile myoclonic epilepsy.« less

Epilepsy in Institutionalized Patients with Encephalopathy: Clinical Aspects and Nosological Considerations.

ERIC Educational Resources Information Center

Mariani, Emilio; And Others

1993-01-01

The prevalence of epilepsy was correlated with the severity and type of encephalopathy of 1,023 individuals with mental retardation. A total of 326 individuals were diagnosed with epilepsy. Results indicated a low percentage of epilepsy in chromosomic-genetic and young adult encephalopathies and a high prevalence when the neurodeficit was…

Management of Hepatic Encephalopathy in the Hospital

PubMed Central

Leise, Michael D.; Poterucha, John J.; Kamath, Patrick S.; Kim, W. Ray

2014-01-01

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

"Symptomatic" infection-associated acute encephalopathy in children with underlying neurological disorders.

PubMed

Hirayama, Yoshimichi; Saito, Yoshiaki; Maegaki, Yoshihiro

2017-03-01

Development of infection-associated acute encephalopathy (AE) is precipitated by several factors, including viral agents, age, and genetic polymorphisms. In addition, children with prior underlying neurological disorders can also present with AE. We reviewed 55 children with AE who were referred to hospitals participating in the Status Epilepticus Study Group from 1988 to 2013. AE was classified into eight subtypes: acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); hemiconvulsion-hemiplegia syndrome (HH); acute necrotizing encephalopathy; hemorrhagic shock and encephalopathy syndrome (HSES); clinically mild encephalitis/encephalopathy with a reversible splenial lesion; acute encephalitis with refractory, repetitive partial seizures; Reye-like syndrome; and unclassified. Of the 55 AE cases, 14 (25.4%) had underlying neurological disorders, including perinatal insults (n=6) and genetic syndrome and/or brain malformations (n=8). These preceding morbidities were relatively common in AESD (6/18, 33.3%), HH (3/9, 33.3%), and HSES (3/6, 50.0%). History of epilepsy or febrile seizures were frequent in HH cases (4/9, 44.4%), whereas they were rare in other AE subtypes. Among the AE subgroups, HH, HSES, and AESD frequently emerged in preceding etiologies with augmented neuronal excitability. These subgroups may have distinct pathomechanism from the "cytokine storm" mediated AEs during childhood. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

USDA-ARS?s Scientific Manuscript database

Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

Genetics Home Reference: ethylmalonic encephalopathy

MedlinePlus

... Tiranti V, Zeviani M. Altered sulfide (H(2)S) metabolism in ethylmalonic encephalopathy. Cold Spring Harb Perspect Biol. 2013 Jan 1;5(1):a011437. doi: 10.1101/cshperspect.a011437. Review. Citation on PubMed or Free article on PubMed Central More from Genetics Home Reference ...

Newborn Bilirubin Screening for Preventing Severe Hyperbilirubinemia and Bilirubin Encephalopathy: A Rapid Review.

PubMed

Bhardwaj, Kalpana; Locke, Tiffany; Biringer, Anne; Booth, Allyson; Darling, Elizabeth K; Dougan, Shelley; Harrison, Jane; Hill, Stephen; Johnson, Ana; Makin, Susan; Potter, Beth; Lacaze-Masmonteil, Thierry; Little, Julian

2017-01-01

According to the 2004 American Academy of Pediatrics guideline on the management of hyperbilirubinemia, every newborn should be assessed for the risk of developing severe hyperbilirubinemia with the help of predischarge total serum bilirubin or transcutaneous bilirubin measurements and/or assessments of clinical risk factors. The aim of this rapid review is 1) to review the evidence for 1) predicting and preventing severe hyperbilirubinemia and bilirubin encephalopathy, 2) determining the efficacy of home/community treatments (home phototherapy) in the prevention of severe hyperbilirubinemia, and 3) non-invasive/transcutaneous methods for estimating serum bilirubin level. In this rapid review, studies were identified through the Medline database. The main outcomes of interest were severe hyperbilirubinemia and encephalopathy. A subset of articles was double screened and all articles were critically appraised using the SIGN and AMSTAR checklists. This review investigated if systems approach is likely to reduce the occurrence of severe hyperbilirubinemia. Fifty-two studies met the inclusion criteria. Included studies assessed the association between bilirubin measurement early in neonatal life and the subsequent development of severe hyperbilirubinemia and chronic bilirubin encephalopathy/kernicterus. It was observed that, highest priority should be given to (i) universal bilirubin screening programs; (ii) implementation of community and midwife practice; (iii) outreach to communities for education of prospective parents; and (iv) development of clinical pathways to monitor, evaluate and track infants with severe hyperbilirubinemia. We found substantial observational evidence that severe hyperbilirubinemia can be accurately predicted and prevented through universal bilirubin screening. So far, there is no evidence of any harm. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Risk factors of ifosfamide-related encephalopathy in adult patients with cancer: A retrospective analysis.

PubMed

Lo, Yin; Shen, Li-Jiuan; Chen, Wen-Hwei; Dong, Yaa-Hui; Wu, Fe-Lin Lin

2016-09-01

Ifosfamide, a widely used chemotherapeutic agent, has been frequently associated with encephalopathy. A larger-scale study was conducted to identify risk factors of ifosfamide-related encephalopathy, including hepatic function. Adult patients who had completed at least one cycle of ifosfamide between January 2008 and December 2010 were included. Those with renal failure or liver failure were excluded. Data were collected through chart review. Patients with encephalopathy and patients without encephalopathy were compared on age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), baseline serum creatinine (SCr) level, albumin level, white blood cell count, liver function, brain metastasis, and dosage of ifosfamide. Chi-square test or Fisher's exact test, Student t test, and univariate and multivariate logistic regressions were used for analysis. This study enrolled 337 patients. Thirty-eight patients (11%) had ifosfamide-related encephalopathy. They had poorer ECOG PS; higher SCr level, white blood cell count, and aspartate aminotransferase level; and lower serum albumin level compared with patients without encephalopathy. Ifosfamide dosage, brain metastasis, and age were not significant risk factors. Multivariate analysis indicated that only ECOG PS, SCr level, and albumin level contributed significantly to the risk. To date, this is the largest-scale study to have analyzed the risk factors of ifosfamide-related encephalopathy. This study confirms that an ECOG PS of 2-4 and increased SCr level are significant risk factors of ifosfamide-related encephalopathy, whereas increased albumin level decreases the risk, consistent with previous reports. Higher aspartate aminotransferase levels have no significant impact. In contrast to previous studies, ifosfamide dosage and brain metastasis are not significant contributing factors. Copyright © 2015. Published by Elsevier B.V.

Intrapartum fever and chorioamnionitis as risks for encephalopathy in term newborns: a case-control study.

PubMed

Blume, Heidi K; Li, Christopher I; Loch, Christian M; Koepsell, Thomas D

2008-01-01

In this study we examined the relationship between diagnoses of isolated intrapartum fever or chorioamnionitis and the risk of encephalopathy in term newborns. We conducted a population-based, case-control study in Washington State using 1994 to 2002 linked data from the Washington State Birth Registry and the Comprehensive Hospital Abstract Reporting System (CHARS). We identified 1060 singleton, term newborns (602 males, 458 females) with International Classification of Diseases (ICD-9) diagnoses consistent with encephalopathy, and 5330 unaffected control newborns (2756 males, 2574 females). Intrapartum fever was defined by a diagnosis of intrapartum temperature of >38 degrees C in the birth registry or CHARS databases. Chorioamnionitis was defined using ICD-9 diagnoses recorded in CHARS. We identified 2.2 cases of encephalopathy per 1000 births. Isolated intrapartum fever was associated with a 3.1-fold (95% confidence interval [CI] 2.3-4.2) increased risk of newborn encephalopathy. Chorioamnionitis was associated with a 5.4-fold (95% CI 3.6-7.8) increased risk of encephalopathy. We found that isolated intrapartum fever and chorioamnionitis were independently associated with an increased risk of encephalopathy in term infants. Our data also indicate that there is a spectrum of risk for encephalopathy in term infants exposed to intrapartum fever. Infants born to women with signs of chorioamnionitis other than isolated intrapartum fever may be at higher risk of encephalopathy than those exposed only to isolated intrapartum fever.

Vogt-Koyanagi-Harada syndrome presenting with encephalopathy

PubMed Central

Naeini, Alireza E.; Daneshmand, Dana; Khorvash, Farzin; Chitsaz, Ahmad

2014-01-01

Vogt-Koyanagi-Harada (VKH) is a rare syndrome affecting tissues containing melanocytes. The possibility of its autoimmune pathogenesis is supported by high frequent HLA-DR4 presentation, commonly associated with other autoimmune diseases. Eyes are the main affected organs, resulting in blindness. Brain disease is a late-onset event, and is extremely rare. Here, we are reporting a 57-year-old woman, a known case of VKH syndrome, presenting with brain encephalopathy several decades after the initial presentation. We think this long period between initial presentation and presentation of encephalopathy due to VKH syndrome has not been described before. She was treated with corticosteroids and discharged home with a good general condition. PMID:24753681

[Portal vein thrombosis associated with hepatic encephalopathy].

PubMed

Iwatani, Nao; Inatomi, Yuichiro; Yonehara, Toshiro; Fujioka, Shodo; Hashimoto, Yoichiro; Hirano, Teruyuki; Uchino, Makoto

2005-03-01

A 54-year-old man who had been administered chlormadinone acetate 3 months after prostatectomy for prostate cancer, acutely developed disorientation and memory disturbance. Six days later, he experienced high grade fever and epigastralgia. He was suspected to have hepatic encephalopathy, because the Fischer ratio was low although serum ammonia level remained normal. Further examinations including abdominal echography and CT scan disclosed a thrombus extending from the portal vein to the superior mesenteric vein together with abnormal collateral vessels originating from the portal vein. He was successfully treated with warfarin potassium, urokinase and heparin sodium. It was suggested that the patient developed hepatic encephalopathy due to portal-systemic circulation shunting secondary to portal vein thrombosis.

Maternal or neonatal infection: association with neonatal encephalopathy outcomes.

PubMed

Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C

2014-07-01

Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index <70 or Bayley Scales of Infant Development, third edition cognitive score <85). Chorioamnionitis was associated with lower risk of moderate-severe brain injury (adjusted odds ratio: 0.3; 95% confidence interval: 0.1-0.7; P = 0.004) and adverse cognitive outcome in children when compared with no chorioamnionitis. Children with signs of neonatal sepsis were more likely to exhibit watershed predominant injury than those without (P = 0.007). Among neonates with encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.

Clinical characteristics of hypertensive encephalopathy in pediatric patients

PubMed Central

Ahn, Chang Hoon; Han, Seung-A; Kong, Young Hwa

2017-01-01

Purpose The aim of this study was to assess the clinical characteristics of hypertensive encephalopathy according to the underlying etiologies in children. Methods We retrospectively evaluated 33 pediatric patients who were diagnosed as having hypertensive encephalopathy in Chonbuk National University Children's Hospital. Among the patients, 18 were excluded because of incomplete data or because brain magnetic resonance imaging (MRI) was not performed. Finally, 17 patients were enrolled and divided into a renal-origin hypertension group and a non-renal-origin hypertension group according to the underlying cause. We compared the clinical features and brain MRI findings between the 2 groups. Results The renal group included renal artery stenosis (4), acute poststreptococcal glomerulonephritis (2), lupus nephritis (2), and acute renal failure (1); the nonrenal group included essential hypertension (4), pheochromocytoma (2), thyrotoxicosis (1), and acute promyelocytic leukemia (1). The mean systolic blood pressure of the renal group (172.5±36.9 mmHg) was higher than that of the nonrenal group (137.1±11.1 mmHg, P<0.05). Seizure was the most common neurologic symptom, especially in the renal group (P<0.05). Posterior reversible encephalopathy syndrome (PRES), which is the most typical finding of hypertensive encephalopathy, was found predominantly in the renal group as compared with the nonrenal group (66.6% vs. 12.5%, P<0.05). Conclusion We conclude that the patients with renal-origin hypertension had a more severe clinical course than those with non-renal-origin hypertension. Furthermore, the renal-origin group was highly associated with PRES on brain MRI. PMID:29042869

Traumatic Brain Injury and Infectious Encephalopathy in Children From Four Resource-Limited Settings in Africa.

PubMed

Fink, Ericka L; von Saint Andre-von Arnim, Amelie; Kumar, Rashmi; Wilson, Patrick T; Bacha, Tigist; Aklilu, Abenezer Tirsit; Teklemariam, Tsegazeab Laeke; Hooli, Shubhada; Tuyisenge, Lisine; Otupiri, Easmon; Fabio, Anthony; Gianakas, John; Kochanek, Patrick M; Angus, Derek C; Tasker, Robert C

2018-04-16

To assess the frequency, interventions, and outcomes of children presenting with traumatic brain injury or infectious encephalopathy in low-resource settings. Prospective study. Four hospitals in Sub-Saharan Africa. Children age 1 day to 17 years old evaluated at the hospital with traumatic brain injury or infectious encephalopathy. None. We evaluated the frequency and outcomes of children presenting consecutively over 4 weeks to any hospital department with traumatic brain injury or infectious encephalopathy. Pediatric Cerebral Performance Category score was assessed pre morbidity and at hospital discharge. Overall, 130 children were studied (58 [45%] had traumatic brain injury) from hospitals in Ethiopia (n = 51), Kenya (n = 50), Rwanda (n = 20), and Ghana (n = 7). Forty-six percent had no prehospital care, and 64% required interhospital transport over 18 km (1-521 km). On comparing traumatic brain injury with infectious encephalopathy, there was no difference in presentation with altered mental state (80% vs 82%), but a greater proportion of traumatic brain injury cases had loss of consciousness (80% vs 53%; p = 0.004). Traumatic brain injury patients were older (median [range], 120 mo [6-204 mo] vs 13 mo [0.3-204 mo]), p value of less than 0.001, and more likely male (73% vs 51%), p value of less than 0.01. In 78% of infectious encephalopathy cases, cause was unknown. More infectious encephalopathy cases had a seizure (69% vs 12%; p < 0.001). In regard to outcome, infectious encephalopathy versus traumatic brain injury: hospital lengths of stay were longer for infectious encephalopathy (8 d [2-30 d] vs 4 d [1-36 d]; p = 0.003), discharge rate to home, or for inpatient rehabilitation, or death differed between infectious encephalopathy (85%, 1%, and 13%) and traumatic brain injury (79%, 12%, and 1%), respectively, p value equals to 0.044. There was no difference in the proportion of children surviving with normal or mild disability (73% traumatic brain injury vs

Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study

PubMed Central

Badawi, Nadia; Kurinczuk, Jennifer J; Keogh, John M; Alessandri, Louisa M; O’Sullivan, Fiona; Burton, Paul R; Pemberton, Patrick J; Stanley, Fiona J

1998-01-01

Objective To ascertain antepartum predictors of newborn encephalopathy in term infants. Design Population based, unmatched case-control study. Setting Metropolitan area of Western Australia, June 1993 to September 1995. Subjects All 164 term infants with moderate or severe newborn encephalopathy; 400 randomly selected controls. Main outcome measures Adjusted odds ratio estimates. Results The birth prevalence of moderate or severe newborn encephalopathy was 3.8/1000 term live births. The neonatal fatality was 9.1%. The risk of newborn encephalopathy increased with increasing maternal age and decreased with increasing parity. There was an increased risk associated with having a mother who was unemployed (odds ratio 3.60), an unskilled manual worker (3.84), or a housewife (2.48). Other risk factors from before conception were not having private health insurance (3.46), a family history of seizures (2.55), a family history of neurological disease (2.73), and infertility treatment (4.43). Risk factors during pregnancy were maternal thyroid disease (9.7), severe pre-eclampsia (6.30), moderate or severe bleeding (3.57), a clinically diagnosed viral illness (2.97), not having drunk alcohol (2.91); and placenta described at delivery as abnormal (2.07). Factors related to the baby were birth weight adjusted for gestational age between the third and ninth centile (4.37) or below the third centile (38.23). The risk relation with gestational age was J shaped with 38 and 39 weeks having the lowest risk. Conclusions The causes of newborn encephalopathy are heterogeneous and many of the causal pathways start before birth. Key messagesThe birth prevalence of moderate or severe newborn encephalopathy was 3.8 per 1000 term live births and the neonatal case fatality was 9.1%Independent risk factors before conception and in the antepartum period for newborn encephalopathy include socioeconomic status, family history of seizures or other neurological disease, conception after

Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate

PubMed Central

Soldovieri, Maria Virginia; Ambrosino, Paolo; Mosca, Ilaria; De Maria, Michela; Moretto, Edoardo; Miceli, Francesco; Alaimo, Alessandro; Iraci, Nunzio; Manocchio, Laura; Medoro, Alessandro; Passafaro, Maria; Taglialatela, Maurizio

2016-01-01

Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K+ current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP2 levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP2 is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies. PMID:27905566

Early-onset epileptic encephalopathy caused by a reduced sensitivity of Kv7.2 potassium channels to phosphatidylinositol 4,5-bisphosphate.

PubMed

Soldovieri, Maria Virginia; Ambrosino, Paolo; Mosca, Ilaria; De Maria, Michela; Moretto, Edoardo; Miceli, Francesco; Alaimo, Alessandro; Iraci, Nunzio; Manocchio, Laura; Medoro, Alessandro; Passafaro, Maria; Taglialatela, Maurizio

2016-12-01

Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K + current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP 2 ). Kv7.2 gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial neonatal seizures to severe early-onset epileptic encephalopathy (Kv7.2-EE). In this study, the biochemical and functional consequences prompted by a recurrent variant (R325G) found independently in four individuals with severe forms of neonatal-onset EE have been investigated. Upon heterologous expression, homomeric Kv7.2 R325G channels were non-functional, despite biotin-capture in Western blots revealed normal plasma membrane subunit expression. Mutant subunits exerted dominant-negative effects when incorporated into heteromeric channels with Kv7.2 and/or Kv7.3 subunits. Increasing cellular PIP 2 levels by co-expression of type 1γ PI(4)P5-kinase (PIP5K) partially recovered homomeric Kv7.2 R325G channel function. Currents carried by heteromeric channels incorporating Kv7.2 R325G subunits were more readily inhibited than wild-type channels upon activation of a voltage-sensitive phosphatase (VSP), and recovered more slowly upon VSP switch-off. These results reveal for the first time that a mutation-induced decrease in current sensitivity to PIP 2 is the primary molecular defect responsible for Kv7.2-EE in individuals carrying the R325G variant, further expanding the range of pathogenetic mechanisms exploitable for personalized treatment of Kv7.2-related epilepsies.

Inflammatory Macrophages Promotes Development of Diabetic Encephalopathy.

PubMed

Wang, Beiyun; Miao, Ya; Zhao, Zhe; Zhong, Yuan

2015-01-01

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.

Encephalopathy in an infant with infantile spasms: possible role of valproate toxicity

PubMed Central

Sivathanu, Shobhana; Sampath, Sowmya; Veerasamy, Madhubala; Sunderkumar, Satheeshkumar

2014-01-01

An infant presented with global developmental delay and infantile spasms. EEG was suggestive of hypsarrhythmia. She was started on sodium valproate, clonazepam and adrenocorticotropic hormone injection. After an initial improvement the child developed vomiting, altered sensorium and increase in frequency of seizures suggestive of encephalopathy. Valproate-induced hyperammonaemia or hepatic encephalopathy was considered and the drug was withheld following which there was a dramatic improvement. Paradoxically, the liver function tests and serum ammonia were normal. However, a complete reversal of encephalopathy, on withdrawal of the drug, strongly suggested an adverse drug reaction (ADR) due to valproic acid. Marginal elevation of serum valproic acid prompted us to use the Naranjo ADR probability score to confirm the diagnosis. This case highlights the fact that valproate toxicity can manifest with normal liver function and serum ammonia levels. This is the youngest reported case with this rare form of valproate-induced encephalopathy. PMID:24810446

Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia.

PubMed

Shellhaas, Renée A; Ng, Chee M; Dillon, Christina H; Barks, John D E; Bhatt-Mehta, Varsha

2013-02-01

Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy are treated with therapeutic hypothermia, and about 40% have clinical seizures. Little is known about the pharmacokinetics of phenobarbital in infants with hypoxic ischemic encephalopathy who undergo therapeutic hypothermia. The objective of this study was to determine the effect of therapeutic hypothermia on phenobarbital pharmacokinetics, taking into account maturational changes. Level 3 neonatal ICU. Infants with hypoxic ischemic encephalopathy and suspected seizures, all treated with phenobarbital. Some of these infants also received treatment with therapeutic hypothermia. None. A retrospective cohort study of 39 infants with hypoxic ischemic encephalopathy treated with phenobarbital (20 were treated with therapeutic hypothermia and 19 were not). Data on phenobarbital plasma concentrations were collected in 39 subjects with hypoxic ischemic encephalopathy with or without therapeutic hypothermia. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. Therapeutic hypothermia did not influence the pharmacokinetic parameters of phenobarbital. Therapeutic hypothermia does not influence the clearance of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for the initial treatment of seizures in neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia.

Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.

PubMed

Guerrini, Renzo; Parrini, Elena

2012-12-01

Rett syndrome is an X-linked neurodevelopmental disorder that manifests in early childhood with developmental stagnation, and loss of spoken language and hand use, with the development of distinctive hand stereotypies, severe cognitive impairment, and autistic features. About 60% of patients have epilepsy. Seizure onset before the age of 3 years is unlikely, and onset after age 20 is rare. Diagnosis of Rett syndrome is based on key clinical elements that identify "typical" Rett syndrome but also "variant" or "atypical" forms. Diagnostic criteria have been modified only slightly over time, even after discovering that MECP2 gene alterations are present in >90% of patients with typical Rett syndrome but only in 50-70% of atypical cases. Over the last several years, intragenic or genomic alterations of the CDKL5 and FOXG1 genes have been associated with severe cognitive impairment, early onset epilepsy and, often, dyskinetic movement disorders, which have variably been defined as Rett variants. It is now clearly emerging that epilepsy has distinctive characteristics in typical Rett syndrome and in the different syndromes caused by CDKL5 and FOXG1 gene alterations. The progressive parting of CDKL5- and FOXG1-gene-related encephalopathies from the core Rett syndrome is reflected by the effort to produce clearer diagnostic criteria for typical and atypical Rett syndrome. Efforts to characterize the molecular pathology underlying these developmental encephalopathies are pointing to abnormalities of telencephalic development, neuronal morphogenesis, maturation and maintenance, and dendritic arborization. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Hepatic encephalopathy caused by congenital extrahepatic portosystemic venous shunt.

PubMed

Ishii, Y; Inagaki, Y; Hirai, K; Aoki, T

2000-01-01

Congenital portosystemic venous shunt is a relatively rare disease. Recently, a 60-year-old woman was admitted to our hospital for hepatic encephalopathy caused by congenital extrahepatic portocaval shunt. She had been in good health until the onset of this event, with no liver damage and no experience of abdominal surgery or history of abdominal trauma. In May 1993, hepatic encephalopathy manifested suddenly, with the chief complaint of orthostatic disturbance. Although conservative treatment was administered during the subsequent 5 years, on admission, liver damage and slight splenomegaly were shown, for which complete resection of the shunt vessel and splenectomy were performed. Postoperatively, the patient's symptoms have been alleviated. Hepatic encephalopathy caused by congenital portosystemic venous shunt requires long-term conservative treatment, and the patient's quality of life is reduced. For this reason, surgical intervention or embolization with interventional radiology should be considered, and the maintenance of hepatic blood flow should also be considered.

Current state of knowledge of hepatic encephalopathy (part IV): Management of Hepatic Encephalopathy by liver support systems.

PubMed

Hassanein, Tarek

2017-04-01

Hepatic Encephalopathy is a devastating complication of End-Stage Liver Disease. In its severe grades it requires extra intervention beyond the standard medical approaches. In this article were view the role of liver support systems in managing hepatic encephalopthy.

Effect of water deionisers on 'fracturing osteodystrophy' and dialysis encephalopathy in Plymouth.

PubMed

Leather, H M; Lewin, I G; Calder, E; Braybrooke, J; Cox, R R

1981-01-01

In the Plymouth area, 95 patients with end-stage renal failure have undergone haemodialysis for 6 months or longer. Of the 47 patients beginning dialysis between 1967 and 1973, when water deionisers were not used routinely, a bone disease with multiple fractures, 'fracturing osteodystrophy', occurred in 18 patients and dialysis encephalopathy in 10. Of the 48 patients first dialysing between 1974 and 1979, when water deionisers used commonly, fracturing osteodystrophy occurred in only one and dialysis encephalopathy also in only one. Duration of dialysis without a water deioniser appeared to be the most important factor in the development of these two conditions. The use of water deionisers usually led to healing of fractures in patients with fracturing osteodystrophy and also led to improvement in 4 of the 11 patients with dialysis encephalopathy. Neither condition has occurred in any patient using a water deioniser from the first dialysis. Water deionisers, therefore, appeared to be effective in both the treatment and prevention of fracturing osteodystrophy and dialysis encephalopathy.

Covert and Overt Hepatic Encephalopathy: Diagnosis and Management

PubMed Central

Patidar, Kavish R.; Bajaj, Jasmohan S.

2015-01-01

Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into two broad categories based on severity, covert (CHE) and overt (CHE). CHE has a significant impact on a patient’s quality of life, driving performances, and has recently 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, it’s imperative for early diagnosis and management. In addition, a focus should also be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of non-absorbable disaccharides, antibiotics (i.e. 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. PMID:26164219

Incidence of posterior reversible encephalopathy syndrome in eclamptic and patients with preeclampsia with neurologic symptoms.

PubMed

Mayama, Michinori; Uno, Kaname; Tano, Sho; Yoshihara, Masato; Ukai, Mayu; Kishigami, Yasuyuki; Ito, Yasuhiro; Oguchi, Hidenori

2016-08-01

Posterior reversible encephalopathy syndrome is observed frequently in patients with eclampsia; however, it has also been reported in some patients with preeclampsia. The aim of this study was to determine the incidence of posterior reversible encephalopathy syndrome in patients with preeclampsia and eclampsia and to assess whether these 2 patient groups share similar pathophysiologic backgrounds by comparing clinical and radiologic characteristics. This was a retrospective cohort study of 4849 pregnant patients. A total of 49 patients with eclampsia and preeclampsia and with neurologic symptoms underwent magnetic resonance imaging and magnetic resonance angiography; 10 patients were excluded from further analysis because of a history of epilepsy or dissociative disorder. The age, parity, blood pressure, and routine laboratory data at the onset of symptoms were also recorded. Among 39 patients with neurologic symptoms, 12 of 13 patients with eclampsia (92.3%) and 5 of 26 patients with preeclampsia (19.2%) experienced the development of posterior reversible encephalopathy syndrome. Whereas age and blood pressure at onset were not significantly different between patients with and without encephalopathy, hematocrit, serum creatinine, aspartate transaminase, alanine transaminase, and lactate dehydrogenase values were significantly higher in patients with posterior reversible encephalopathy syndrome than in those without magnetic resonance imaging abnormalities. In contrast, patients with eclampsia with posterior reversible encephalopathy syndrome did not show any significant differences in clinical and laboratory data compared with patients with preeclampsia with posterior reversible encephalopathy syndrome. In addition to the parietooccipital regions, atypical regions (such as the frontal and temporal lobes), and basal ganglia were also involved in patients with eclampsia and patients with preeclampsia with posterior reversible encephalopathy syndrome. Finally

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

PubMed

Chen, Xiao-Qiao; Zhang, Wei-Na; Hu, Lin-Yan; Liu, Meng-Jia; Zou, Li-Ping

2016-03-01

Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes.

PubMed

Van Esch, Hilde; Jansen, Anna; Bauters, Marijke; Froyen, Guy; Fryns, Jean-Pierre

2007-02-15

We describe a male patient with a deletion at Xp22, detected by high resolution X-array CGH. The clinical phenotype present in this infant boy, consists of severe encephalopathy, congenital cataracts and tetralogy of Fallot and can be attributed to the deletion of the genes within the interval. Among these deleted genes are the gene for Nance-Horan syndrome and the cyclin-dependent kinase-like 5 gene (CDKL5), responsible for the early seizure variant of Rett syndrome. This is the first description of a male patient with a deletion of these genes, showing the involvement of CDKL5 in severe epileptic encephalopathy in males. Moreover it illustrates the added value of high resolution array-CGH in molecular diagnosis of mental retardation-multiple congenital anomaly cases. (c) 2007 Wiley-Liss, Inc.

Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

PubMed

Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

2016-10-01

Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea.

PubMed

Byun, Jung-Ick; Lee, Soon-Tae; Jung, Keun-Hwa; Sunwoo, Jun-Sang; Moon, Jangsup; Kim, Tae-Joon; Lim, Jung-Ah; Kim, Soyun; Kim, Do-Yong; Han, Su-Hyun; Jang, Hyemin; Suh, Hong Il; Cho, A-Hyun; Kim, Dong Wook; Shin, Jung-Won; Koo, Yong Seo; Choi, Woo Chan; Lee, Woong-Woo; Choi, Nari; Kim, Seongheon; Nam, Hyunwoo; Koo, Dae Lim; Kim, Minah; Lim, Byung Chan; Chae, Jong-Hee; Kim, Ki Joong; Jeon, Daejong; Park, Kyung-Il; Jung, Ki-Young; Kim, Manho; Chu, Kon; Lee, Sang Kun

2016-04-15

We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause. Copyright © 2016 Elsevier B.V. All rights reserved.

Origin and implications of bovine spongiform encephalopathy.

PubMed

Narang, H

1996-04-01

All spongiform encephalopathies in animals, including humans, are slow developing infectious diseases. The current working theory links the origin of bovine spongiform encephalopathy (BSE) to the feeding of cattle with meat and bone meal prepared from scrapie-infected sheep remains. Recycling of cattle meat and bones (MBM) essentially resulted in the selection of a single strain from the "wild type", a mixture of 20 strains. The BSE agent is easily transmitted through ingestion, with some evidence of vertical transmission. Paradoxically, cattle have selected a major new strain which appears to be more virulent than an unselected strain found in scrapie sheep. The same strain of BSE agent is implicated in the occurrence of spongiform encephalopathy in domestic cats, tiger, and some exotic species of ruminants in zoos. The properties of BSE and its spread into cattle are still disputed. Since our understanding of the disease and its transmissibility in humans must await observations that will be made over some years to come, it is important to keep a reasonable perspective and ensure that any speculative comment is consistent with fact. In risk assessment in such circumstances, it is tempting give too much credence to persuasive parallels when direct relevant information is not available. On the other hand, it would also not be wise to assume that the disease will die by itself and will have no effect on humans.

Executive functions and psychiatric symptoms in drug-refractory juvenile myoclonic epilepsy.

PubMed

Walsh, Jordana; Thomas, Rhys H; Church, Carla; Rees, Mark I; Marson, Anthony G; Baker, Gus A

2014-06-01

The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related. Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured. Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores. This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery. Copyright © 2014. Published by Elsevier Inc.

Correlation of hyponatremia with hepatic encephalopathy and severity of liver disease.

PubMed

Qureshi, Muhammad Omar; Khokhar, Nasir; Saleem, Atif; Niazi, Tariq Khan

2014-02-01

To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital. Observational study. Shifa International Hospital, Islamabad, from January 2011 to January 2012. A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p < 0.001). Hyponatremia was a common feature in patients with cirrhosis and its severity increased with the severity of liver disease. The existence of serum sodium concentration < 135 mmol/L was associated with greater frequency of hepatic encephalopathy compared with patients with serum sodium concentration > 135 mmol/L.

The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia.

PubMed

Thorsen, Patricia; Jansen-van der Weide, Martine C; Groenendaal, Floris; Onland, Wes; van Straaten, Henrika L M; Zonnenberg, Inge; Vermeulen, Jeroen R; Dijk, Peter H; Dudink, Jeroen; Rijken, Monique; van Heijst, Arno; Dijkman, Koen P; Cools, Filip; Zecic, Alexandra; van Kaam, Anton H; de Haan, Timo R

2016-07-01

The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed. The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia. The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied. Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (interquartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score ≥12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8). The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated

Cooling for newborns with hypoxic ischaemic encephalopathy.

PubMed

Jacobs, Susan E; Berg, Marie; Hunt, Rod; Tarnow-Mordi, William O; Inder, Terrie E; Davis, Peter G

2013-01-31

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

Brain MRI findings in acute hepatic encephalopathy in liver transplant recipients.

PubMed

Guo, Ruo-Mi; Li, Qing-Ling; Zhong, Li-Ru; Guo, Yu; Jiao, Ju; Chen, Shao-Qiong; Wang, Jin; Zhang, Yong

2018-06-01

Acute hepatic encephalopathy has significant morbidity and mortality in liver transplant recipients unless it is promptly treated. We evaluated the brain magnetic resonance (MR) imaging findings associated with acute hepatic encephalopathy in transplant recipients. We retrospectively reviewed the clinical and imaging data and outcomes of twenty-five liver transplant patients (16 male; mean age, 49.3 years) with clinically diagnosed acute hepatic encephalopathy and forty liver transplant patients (20 males; mean age, 45.5 years) without neurological symptoms suggestive of hepatic encephalopathy at our institution. Bilateral symmetric hyperintensities of the insular cortex and cingulate gyrus were observed in twenty-one patients (84.00%), bilateral symmetric extensive increased cortical signal intensity (involving two or more regions) was observed in 72.00% of the patients, leptomeningeal enhancement in 73.68%, and visualization of prominent venules in 52.00%. The most common symptom at diagnosis was rigidity (n = 14), and the plasma ammonia levels ranged from 68.63 to 192.16 μmol/L. After active treatment, 17 patients gradually recovered, four patients suffered from mild or moderate neurologic deficits, and four patients with widespread brain edema died. The specific brain MR imaging features were bilateral symmetric increased cortical signal intensity, especially in the insular cortex and cingulate gyrus, leptomeningeal enhancement, visualization of the prominent venules, and widespread brain edema. These features may indicate poor prognosis and should alert radiologists to the possibility of acute hepatic encephalopathy in liver transplant recipients and encourage clinicians to prepare appropriate treatment in advance.

Metronidazole-induced encephalopathy in a patient with Crohn's disease

PubMed Central

Kim, Jihye; Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kang, Jin Woo; Hwang, Seongjun; Ko, Sang-Bae; Im, Jong Pil; Kim, Joo Sung

2017-01-01

Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. PMID:28239323

Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy.

PubMed

Doman, Sydney E; Girish, Akanksha; Nemeth, Christina L; Drummond, Gabrielle T; Carr, Patrice; Garcia, Maxine S; Johnston, Michael V; Kannan, Sujatha; Fatemi, Ali; Zhang, Jiangyang; Wilson, Mary Ann

2018-01-01

Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome. Mice were subjected to HI (unilateral carotid ligation followed by exposure to hypoxia) on postnatal day 7 and were imaged with T2-weighted MRI and diffusion-weighted MRI (DWI), 3 h after HI. Clearly defined regions of increased signal were comparable in T2 MRI and DWI, and we found a strong correlation between T2 MRI injury scores 3 h after HI and histopathological brain injury 7 days after HI, validating this method for evaluating initial injury in this model of HIE. The more efficient, higher resolution T2 MRI was used to score initial brain injury in subsequent studies. In mice treated with hypothermia, we found a significant reduction in T2 MRI injury scores 3 h after HI, compared to normothermic littermates. Early hypothermic neuroprotection was maintained 7 days after HI, in both T2 MRI injury scores and histopathology. In the normothermic group, T2 MRI injury scores 3 h after HI were comparable to those obtained 7 days after HI. However, in the hypothermic group, brain injury was significantly less 7 days after HI than at 3 h. Thus, early neuroprotective effects of hypothermia were enhanced by 7 days, which may reflect the additional 3 h of hypothermia after imaging or effects on later mechanisms of injury, such as delayed cell

Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy

PubMed Central

Doman, Sydney E.; Girish, Akanksha; Nemeth, Christina L.; Drummond, Gabrielle T.; Carr, Patrice; Garcia, Maxine S.; Johnston, Michael V.; Kannan, Sujatha; Fatemi, Ali; Zhang, Jiangyang; Wilson, Mary Ann

2018-01-01

Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome. Mice were subjected to HI (unilateral carotid ligation followed by exposure to hypoxia) on postnatal day 7 and were imaged with T2-weighted MRI and diffusion-weighted MRI (DWI), 3 h after HI. Clearly defined regions of increased signal were comparable in T2 MRI and DWI, and we found a strong correlation between T2 MRI injury scores 3 h after HI and histopathological brain injury 7 days after HI, validating this method for evaluating initial injury in this model of HIE. The more efficient, higher resolution T2 MRI was used to score initial brain injury in subsequent studies. In mice treated with hypothermia, we found a significant reduction in T2 MRI injury scores 3 h after HI, compared to normothermic littermates. Early hypothermic neuroprotection was maintained 7 days after HI, in both T2 MRI injury scores and histopathology. In the normothermic group, T2 MRI injury scores 3 h after HI were comparable to those obtained 7 days after HI. However, in the hypothermic group, brain injury was significantly less 7 days after HI than at 3 h. Thus, early neuroprotective effects of hypothermia were enhanced by 7 days, which may reflect the additional 3 h of hypothermia after imaging or effects on later mechanisms of injury, such as delayed cell

Human herpesvirus-6 infection-associated acute encephalopathy without skin rash.

PubMed

Yamamoto, Shiho; Takahashi, Satoru; Tanaka, Ryosuke; Okayama, Akie; Araki, Akiko; Katano, Harutaka; Tanaka-Taya, Keiko; Azuma, Hiroshi

2015-09-01

Human herpesvirus-6 (HHV-6) is the etiological agent of exanthema subitum-associated encephalopathy, which usually occurs in children younger than 3 years. Brain imaging shows various abnormalities. A previously healthy 4-year-old girl developed acute encephalopathy with clinical features consisting of fever, repetitive seizures, and a disturbance of consciousness. The patient did not show skin rash suggestive of exanthema subitum during the course of her illness. The primary HHV-6 infection was diagnosed based on the absence of IgG against HHV-6 and identification of the virus DNA in the acute phase serum and a significant increase of the anti-HHV-6 IgG titers in the convalescent phase sera. Diffusion-weighted images showed transient high signal intensity in the bilateral periventricular white matter and splenium of the corpus callosum and in the gray matter structures such as the bilateral basal ganglia and thalami. Upon therapy with steroid and γ-globulin, the patient recovered without any neurological deficits. Primary HHV-6 infection can cause acute encephalopathy without exanthema subitum. The etiological diagnosis is possible only by examining the blood and cerebrospinal fluid, when the patient shows no skin rash. This condition should be included in the differential diagnosis of acute encephalopathy even in patients older than 3 years. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes.

PubMed

Patel, Jaina; Mercimek-Mahmutoglu, Saadet

2016-10-01

Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy.

Adult onset urea cycle disorder in a patient with presumed hepatic encephalopathy.

PubMed

Atiq, Muslim; Holt, Andrew F; Safdar, Kamran; Weber, Frederick; Ravinuthala, Ravi; Jonas, Mark E; Neff, Guy W

2008-02-01

Deficiency of any of the 5 enzymes in the urea cycle results in the accumulation of ammonia, leading to encephalopathy; which if untreated, can be lethal and produce devastating neurologic sequelae in long-term survivors. We hereby present an interesting case that presented with hyperammonemia and encephalopathy; later found to have an urea cycle defect.

A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection.

PubMed

Hwang, J-Y; Kim, J-H; Oh, A-Y; Do, S-H; Jeon, Y-T; Han, S-H

2008-01-01

Etomidate is a popular anaesthetic induction agent, but it frequently causes myoclonic movements. Although both benzodiazepines and opioids reduce myoclonus, there has been no comparative study between these agents. Thus, we conducted a prospective, randomized study to compare midazolam and remifentanil as pre-treatment agents for reducing etomidate-induced myoclonus in 90 adults undergoing surgery. Patients were pre-treated before the etomidate injection, either with saline (Group C), midazolam 0.5 mg/kg (Group M) or remifentanil 1 microg/kg (Group R). Both Groups M and R showed a significantly lower incidence of myoclonus compared with Group C (17%, 17% and 77%, respectively). The incidence of myoclonus was not significantly different between Groups M and R, but 10% (n = 10) of the patients in Group R experienced remifentanil-related side-effects. We conclude that midazolam is probably a better choice than remifentanil for reducing etomidate-induced myoclonus during anaesthesia induction.

Septic encephalopathy and septic encephalitis‬‬.

PubMed

Tauber, Simone C; Eiffert, Helmut; Brück, Wolfgang; Nau, Roland

2017-02-01

During the last two decades, septic encephalopathy (SE) was recognized as a clinically relevant problem with a high prevalence in patients at admission and during their hospital stay. SE is a condition associated with increased mortality and morbidity such as long-term cognitive impairment. Areas covered: This review illustrates the pathophysiology of sepsis-associated encephalopathy and encephalitis involving blood-brain-barrier dysfunction and neuroinflammation caused by endothelial and microglial activation by endogenous or pathogen-derived compounds, hypoxia by impaired microvascular regulation and septic shock as well as imbalance of neurotransmitters. The continuum between septic-embolic and septic-metastatic encephalitis and SE is underlined by histological findings. The options of technical examinations and biomarkers to diagnose SE are discussed together with established therapeutic options as well as current experimental approaches. Expert commentary: An outlook for clinicians is provided including promising diagnostic approaches by means of new imaging techniques. Clinical trials with drugs already established for other indications such as statins, erythropoietin and minocycline are warranted in the future.

More than meets the eye: infant presenting with hypoxic ischaemic encephalopathy.

PubMed

Sen, Kuntal; Agarwal, Rajkumar

2018-04-05

We report a newborn infant who presented with poor Apgar scores and umbilical artery acidosis leading to the diagnosis of hypoxic ischaemic encephalopathy. During the course of the infant's hospitalisation, subsequent workup revealed an underlying genetic cause that masqueraded as hypoxic ischaemic encephalopathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PRIONS AND THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

EPA Science Inventory

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...

The clinical outcome and neuroimaging of acute encephalopathy after status epilepticus in Dravet syndrome.

PubMed

Tian, Xiaojuan; Ye, Jintang; Zeng, Qi; Zhang, Jing; Yang, Xiaoling; Liu, Aijie; Yang, Zhixian; Liu, Xiaoyan; Wu, Xiru; Zhang, Yuehua

2018-06-01

To analyze the clinical outcome and neuroimaging over a long duration follow-up in the currently largest series of acute encephalopathy after status epilepticus in patients with Dravet syndrome. Clinical and neuroimaging data of patients with Dravet syndrome with a history of acute encephalopathy (coma >24h) after status epilepticus from February 2005 to December 2016 at Peking University First Hospital were reviewed retrospectively. Thirty-five patients (15 males, 20 females) with a history of acute encephalopathy were enrolled from a total of 624 patients with Dravet syndrome (5.6%). The median onset age of acute encephalopathy was 3 years 1 month. The duration of status epilepticus varied between 40 minutes to 12 hours. Thirty-four patients had a high fever when status epilepticus occurred, and only one had a normal temperature. Coma lasted from 2 to 20 days. Twelve patients died and 23 survived with massive neurological regression. The median follow-up time was 2 years 1 month. Neuroimaging of 20 out of 23 survivors during the recovery phase showed diverse degrees of cortical atrophy with or without subcortical lesions. Acute encephalopathy after status epilepticus is more prone to occur in patients with Dravet syndrome who had a high fever. The mortality rate is high in severe cases. Survivors are left with severe neurological sequelae but often with either no seizure or low seizure frequency. Acute encephalopathy is more prone to occur in patients with Dravet syndrome with a high fever. The mortality rate is high for acute encephalopathy after status epilepticus in patients with Dravet syndrome. Survivors have neurological sequelae. © 2018 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.

Minimal hepatic encephalopathy matters in daily life

PubMed Central

Bajaj, Jasmohan S

2008-01-01

Minimal hepatic encephalopathy is a neuro-cognitive dysfunction which occurs in an epidemic proportion of cirrhotic patients, estimated as high as 80% of the population tested. It is characterized by a specific, complex cognitive dysfunction which is independent of sleep dysfunction or problems with overall intelligence. Although named “minimal”, minimal hepatic encephalopathy (MHE) can have a far-reaching impact on quality of life, ability to function in daily life and progression to overt hepatic encephalopathy. Importantly, MHE has a profound negative impact on the ability to drive a car and may be a significant factor behind motor vehicle accidents. A crucial aspect of the clinical care of MHE patients is their driving history, which is often ignored in routine care and can add a vital dimension to the overall disease assessment. Driving history should be an integral part of care in patients with MHE. The lack of specific signs and symptoms, the preserved communication skills and lack of insight make MHE a difficult condition to diagnose. Diagnostic strategies for MHE abound, but are usually limited by financial, normative or time constraints. Recent studies into the inhibitory control and critical flicker frequency tests are encouraging since these tests can increase the rates of MHE diagnosis without requiring a psychologist. Although testing for MHE and subsequent therapy is not standard of care at this time, it is important to consider this in cirrhotics in order to improve their ability to live their life to the fullest. PMID:18595126

Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A computational study.

PubMed

Ruijter, B J; Hofmeijer, J; Meijer, H G E; van Putten, M J A M

2017-09-01

In postanoxic coma, EEG patterns indicate the severity of encephalopathy and typically evolve in time. We aim to improve the understanding of pathophysiological mechanisms underlying these EEG abnormalities. We used a mean field model comprising excitatory and inhibitory neurons, local synaptic connections, and input from thalamic afferents. Anoxic damage is modeled as aggravated short-term synaptic depression, with gradual recovery over many hours. Additionally, excitatory neurotransmission is potentiated, scaling with the severity of anoxic encephalopathy. Simulations were compared with continuous EEG recordings of 155 comatose patients after cardiac arrest. The simulations agree well with six common categories of EEG rhythms in postanoxic encephalopathy, including typical transitions in time. Plausible results were only obtained if excitatory synapses were more severely affected by short-term synaptic depression than inhibitory synapses. In postanoxic encephalopathy, the evolution of EEG patterns presumably results from gradual improvement of complete synaptic failure, where excitatory synapses are more severely affected than inhibitory synapses. The range of EEG patterns depends on the excitation-inhibition imbalance, probably resulting from long-term potentiation of excitatory neurotransmission. Our study is the first to relate microscopic synaptic dynamics in anoxic brain injury to both typical EEG observations and their evolution in time. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network Encephalopathy Registry

PubMed Central

Bingham, Peter; Edwards, Erika M.; Horbar, Jeffrey D.; Kenny, Michael J.; Inder, Terrie; Pfister, Robert H.; Raju, Tonse; Soll, Roger F.

2012-01-01

BACKGROUND: Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE. OBJECTIVES: To identify antecedents in a large registry of infants who had NE. METHODS: This was a maternal and infant record review of 4165 singleton neonates, gestational age of ≥36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry. RESULTS: Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of ≤3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of ≥37.5°C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination. CONCLUSIONS: Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained. PMID:23071210

Comparison of Rifaximin Plus Lactulose with the Lactulose Alone for the Treatment of Hepatic Encephalopathy.

PubMed

Ahire, Kiran; Sonawale, Archana

2017-08-01

Hepatic encephalopathy is challenging complication of liver dysfunction. Therapeutic treatment options for hepatic encephalopathy are currently limited and have appreciable risks and benefits associated with their use. Rifaximin is a novel anti microbiological agent with wide spectrum of activity that has shown promise as an alternative option for hepatic encephalopathy. The present study was undertaken to compare the effectiveness of Rifaximin and Lactulose as a combination vs Lactulose alone, to compare the adverse effects and to study the rapidity of therapeutic effects of Rifaximin and Lactulose. It was a prospective observational study. 60 patients suffering from hepatic encephalopathy (HE) were studied. Patients were investigated and treated as per treating physician's decision. At the time of analysis, patients were divided into 2 groups, Rifaximin group who received Rifaximin+Lactulose (R+L) and Lactulose group(L), who received Lactulose only. Parameters such as mental status grade, Asterixis grade, Serum Ammonia grade, Number Connection Test grade (NCT grade), Hepatic Encephalopathy Index (HE index) were evaluated and compared in both groups. Clinical efficacy was determined using HE index improvement. Primary end points were decrease in HE index and reversal of HE grades. Secondary end points were mortality from HE or any other cause, decrease in mental status grade, asterixis grade, serum Ammonia grade, NCT grade. Out of 60 patients, 32 received Rifaximin+Lactulose combination and 28 patients received Lactulose alone. Mean Child-Turcotte-Pugh score (CTP score) was 10.6 in R+L group and 10.32 in L group. There was statistically significant improvement in mental status grade, Asterixis grade, Serum Ammonia grade, NCT grade, Hepatic encephalopathy index in both groups, p value <0.05 but no statistically significant difference between improvement in mental status grade, Asterixis grade, Serum Ammonia grade, NCT grade, HE index between the two groups

Genetics Home Reference: acute necrotizing encephalopathy type 1

MedlinePlus

... the signs and symptoms of this condition. The health history of the individual, such as nutritional status and number of prior ... (1 link) Genetic Testing Registry: Encephalopathy, acute, infection- ...

Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy.

PubMed

Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

2015-01-01

The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration.

Primary hypothyroidism masquerading as hepatic encephalopathy: case report and review of the literature

PubMed Central

Thobe, N.; Pilger, P.; Jones, M.

2000-01-01

A 74 year old woman with hepatitis C of long duration was admitted to hospital in hyperammonaemic coma. Despite aggressive treatment of hepatic encephalopathy, there was no clinical improvement. As part of her evaluation for other causes of altered mental status, she was found to be profoundly hypothyroid. Treatment with thyroid replacement hormone was accompanied by prompt normalisation of her mental status and hyperammonaemia. Hypothyroidism may exacerbate hyperammonaemia and portosystemic encephalopathy in patients with otherwise well compensated liver disease. Hyopthyroidism should be considered in the differential diagnosis of encephalopathy in patients with liver disease.


Keywords: hypothyroidism; cirrhosis; hyperammonaemia; coma PMID:10878207

How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist

PubMed Central

Dunk, Arthur A.; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J.; Laleman, Wim; Ramage, John K.; Wedemeyer, Heiner; Morgan, Ian E.J.

2016-01-01

Introduction Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of ‘consensus points’ to provide some guidance on management. Methods Using a modified ‘Delphi’ process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Results Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Conclusion Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a ‘suspicion’ of cognitive impairment through to a formal diagnosis of hepatic encephalopathy. PMID:26600154

How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist.

PubMed

Shawcross, Debbie L; Dunk, Arthur A; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J; Laleman, Wim; Ramage, John K; Wedemeyer, Heiner; Morgan, Ian E J

2016-02-01

Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of 'consensus points' to provide some guidance on management. Using a modified 'Delphi' process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a 'suspicion' of cognitive impairment through to a formal diagnosis of hepatic encephalopathy.

[Acute encephalopathy due to late-onset maple syrup urine disease in a school boy].

PubMed

Qu, Su-Qing; Yang, Li-Cai; Luan, Zuo; Du, Kan; Yang, Hui

2012-03-01

Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-02-25

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index on 2 October 2014. We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2017-05-18

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index - Science, and LILACS (May 2017). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous

Branched-chain amino acids for people with hepatic encephalopathy.

PubMed

Gluud, Lise Lotte; Dam, Gitte; Les, Iñigo; Córdoba, Juan; Marchesini, Giulio; Borre, Mette; Aagaard, Niels Kristian; Vilstrup, Hendrik

2015-09-17

Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index (August 2015). We included randomised clinical trials, irrespective of the bias control, language, or publication status. The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small-study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials

Bovine Spongiform Encephalopathy: Atypical Pros and Cons

USDA-ARS?s Scientific Manuscript database

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...

Improving the Identification of Neonatal Encephalopathy: Utility of a Web-Based Video Tool.

PubMed

Ivy, Autumn S; Clark, Catherine L; Bahm, Sarah M; Meurs, Krisa P Van; Wusthoff, Courtney J

2017-04-01

Objective  This study tested the effectiveness of a video teaching tool in improving identification and classification of encephalopathy in infants. Study Design  We developed an innovative video teaching tool to help clinicians improve their skills in interpreting the neonatal neurological examination for grading encephalopathy. Pediatric residents were shown 1-minute video clips demonstrating exam findings in normal neonates and neonates with various degrees of encephalopathy. Findings from five domains were demonstrated: spontaneous activity, level of alertness, posture/tone, reflexes, and autonomic responses. After each clip, subjects were asked to identify whether the exam finding was normal or consistent with mild, moderate, or severe abnormality. Subjects were then directed to a web-based teaching toolkit, containing a compilation of videos demonstrating normal and abnormal findings on the neonatal neurological examination. Immediately after training, subjects underwent posttesting, again identifying exam findings as normal, mild, moderate, or severe abnormality. Results  Residents improved in their overall ability to identify and classify neonatal encephalopathy after viewing the teaching tool. In particular, the identification of abnormal spontaneous activity, reflexes, and autonomic responses were most improved. Conclusion  This pretest/posttest evaluation of an educational tool demonstrates that after viewing our toolkit, pediatric residents were able to improve their overall ability to detect neonatal encephalopathy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

L-ornithine-L-aspartate infusion efficacy in hepatic encephalopathy.

PubMed

Ahmad, Irfan; Khan, Anwaar A; Alam, Altaf; Dilshad, Akif; Butt, Arshad Kamal; Shafqat, Farzana; Malik, Kashif; Sarwar, Shahid

2008-11-01

To determine the efficacy of L-ornithine-L-aspartate in treatment of hepatic encephalopathy. Randomized, placebo-controlled trial. Department of Gastroenterology and Hepatology, Sheikh Zayed Hospital, Lahore, from February to August 2005. Cirrhotic patients with hyperammonemia and overt hepatic encephalopathy were enrolled. Eighty patients were randomized to two treatment groups, L-ornithine-L-aspartate (20 g/d) or placebo, both dissolved in 250 mL of 5% dextrose water and infused intravenously for four hours a day for five consecutive days with 0.5 g/kg dietary protein intake at the end of daily treatment period. Outcome variables were postprandial blood ammonia and mental state grade. Adverse reactions and mortality were also determined. Both treatment groups were comparable regarding age, gender, etiology of cirrhosis, Child-Pugh class, mental state grade and blood ammonia at baseline. Although, improvement occurred in both groups, there was a greater improvement in L-ornithine-L-aspartate group with regard to both variables. Four patients in the placebo group and 2 in L-ornithine-L-aspartate group died. L-ornithine-L-aspartate infusions were found to be effective in cirrhotic patients with hepatic encephalopathy.

Low plasma magnesium is associated with impaired brain metabolism in neonates with hypoxic-ischaemic encephalopathy.

PubMed

Chakkarapani, Elavazhagan; Chau, Vann; Poskitt, Kenneth J; Synnes, Anne; Kwan, Eddie; Roland, Elke; Miller, Steven P

2016-09-01

To determine the association between lowest plasma magnesium concentration and brain metabolism, and whether magnetic resonance imaging brain injury patterns moderated the association in hypoxic-ischemic encephalopathy. In 131 early (day-of-life 3) and 65 late (day-of-life 10) scans of term encephalopathic infants born between 2004 and 2012, we examined the association of lowest plasma magnesium (until day-of-life 3) on basal ganglia and white matter peak metabolite ratios on magnetic resonance spectroscopy independent of covariates, stratified by the predominant patterns of injury (normal, basal nuclei/total, watershed, multifocal) using multiple linear regression. Lowest plasma magnesium was associated with lower white matter N-acetyl-aspartate/choline in the multifocal pattern on early scan (regression-coefficient, β: 0.13; 95% CI: 0.04, 0.22) and in the basal nuclei/total pattern on late scan (β: 0.08; 95% CI: 0.02, 0.15), and was negatively associated with basal ganglia lactate/N-acetyl-aspartate (β: -0.16; 95% CI: -0.05, -0.28) and lactate/choline (β: -0.1; 95% CI: -0.03, -0.17) ratio in the basal nuclei/total pattern on late scan independent of hypomagnesaemia correction, cooling and postmenstrual age at scan. Lowest plasma magnesium was not associated with metabolite ratios in other brain injury patterns. In infants with hypoxic-ischaemic encephalopathy, predominant patterns of brain injury moderated the association between lowest plasma magnesium in the first three days of life and impaired brain metabolism. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

PubMed Central

2011-01-01

Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations. PMID:22035425

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

PubMed

Swartz, B E; Spitz, J; Vu, A L; Mandelkern, M; Su, M L

2016-10-01

To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy

PubMed Central

Yamamoto, Toshiyuki; Shimojima, Keiko; Kimura, Nobusuke; Mogami, Yukiko; Usui, Daisuke; Takayama, Rumiko; Ikeda, Hiroko; Imai, Katsumi

2015-01-01

The cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration. PMID:27081548

Early discontinuation of antiseizure medications in neonates with hypoxic-ischemic encephalopathy.

PubMed

Fitzgerald, Mark P; Kessler, Sudha Kilaru; Abend, Nicholas S

2017-06-01

Neonates with hypoxic-ischemic encephalopathy (HIE) managed with therapeutic hypothermia (TH) often experience acute symptomatic seizures, prompting treatment with antiseizure medications (ASMs). Because the risk of seizure occurrence after hospital discharge is unknown, the optimal ASM treatment duration is unclear. We aimed to determine the risk of seizure occurrence after hospital discharge and the impact of ASM treatment duration on this outcome. We performed a single-center, retrospective study of consecutive neonates with HIE managed with TH who received ASMs for acute symptomatic seizures from June 2010 through December 2014. Neonates were monitored with continuous electroencephalography (EEG) during TH. Follow-up data were available for 59 (82%) of 72 neonates who survived to discharge, with a median follow-up period of 19 months (interquartile range [IQR] 11-25). Acute symptomatic seizures occurred in 35 neonates (59%), including electrographic seizures in 21 neonates (36%). ASMs were continued upon discharge in 17 (49%) of 35 neonates. Seizures occurred in follow-up in four neonates (11%). No patient for whom ASMs were discontinued prior to discharge experienced seizures during the follow-up period. Among neonates with HIE, seizures after hospital discharge were rare in those with acute symptomatic seizures and did not occur in neonates without acute symptomatic seizures. ASM discontinuation prior to discharge did not increase the risk of seizures during the follow-up period, suggesting that ASMs may be discontinued in many neonates prior to discharge. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Experimental Inoculation of Spiroplasma mirum and Transmissible Mink Encephalopathy (TME) into Raccoons (Procyon lotor)

USDA-ARS?s Scientific Manuscript database

To determine if Spiroplasma mirum would be capable of producing lesions of spongiform encephalopathy in raccoons (Procyon lotor), 5 groups (n = 5) of raccoon kits were inoculated intracerebrally with either S. mirum and/or transmissible mink encephalopathy (TME). Two other groups (n = 5) of raccoon...

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

PubMed

Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

2017-09-01

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

DNM1 encephalopathy

PubMed Central

von Spiczak, Sarah; Helbig, Katherine L.; Shinde, Deepali N.; Huether, Robert; Pendziwiat, Manuela; Lourenço, Charles; Nunes, Mark E.; Sarco, Dean P.; Kaplan, Richard A.; Dlugos, Dennis J.; Kirsch, Heidi; Slavotinek, Anne; Cilio, Maria R.; Cervenka, Mackenzie C.; Cohen, Julie S.; McClellan, Rebecca; Fatemi, Ali; Yuen, Amy; Sagawa, Yoshimi; Littlejohn, Rebecca; McLean, Scott D.; Hernandez-Hernandez, Laura; Maher, Bridget; Møller, Rikke S.; Palmer, Elizabeth; Lawson, John A.; Campbell, Colleen A.; Joshi, Charuta N.; Kolbe, Diana L.; Hollingsworth, Georgie; Neubauer, Bernd A.; Muhle, Hiltrud; Stephani, Ulrich; Scheffer, Ingrid E.; Pena, Sérgio D.J.; Sisodiya, Sanjay M.

2017-01-01

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. Methods: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. Results: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. Conclusions: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention. PMID:28667181

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin.

PubMed

Barker, Bryan S; Ottolini, Matteo; Wagnon, Jacy L; Hollander, Rachel M; Meisler, Miriam H; Patel, Manoj K

2016-09-01

SCN8A encephalopathy (early infantile epileptic encephalopathy; EIEE13) is caused by gain-of-function mutations resulting in hyperactivity of the voltage-gated sodium channel Nav 1.6. The channel is concentrated at the axon initial segment (AIS) and is involved in establishing neuronal excitability. Clinical features of SCN8A encephalopathy include seizure onset between 0 and 18 months of age, intellectual disability, and developmental delay. Seizures are often refractory to treatment with standard antiepileptic drugs, and sudden unexpected death in epilepsy (SUDEP) has been reported in approximately 10% of patients. In a recent study, high doses of phenytoin were effective in four patients with SCN8A encephalopathy. In view of this observation, we have investigated the relationship between the functional effect of the SCN8A mutation p.Ile1327Val and its response to phenytoin. The mutation was introduced into the Scn8a cDNA by site-directed mutagenesis. Channel activity was characterized in transfected ND7/23 cells. The effects of phenytoin (100 μm) on mutant and wild-type (WT) channels were compared. Channel activation parameters were shifted in a hyperpolarizing direction in the mutant channel, whereas inactivation parameters were shifted in a depolarizing direction, increasing Na channel window current. Macroscopic current decay was slowed in I1327V channels, indicating an impairment in the transition from open state to inactivated state. Channel deactivation was also delayed, allowing more channels to remain in the open state. Phenytoin (100 μm) resulted in hyperpolarized activation and inactivation curves as well as greater tonic block and use-dependent block of I1327V mutant channels relative to WT. SCN8A - I1327V is a gain-of-function mutation with altered features that are predicted to increase neuronal excitability and seizure susceptibility. Phenytoin is an effective inhibitor of the mutant channel and may be of use in treating patients with gain

Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of reversible cognitive impairment

PubMed Central

Maroz, Natallia; Bernhardt, Nechama; Chow, Robert Dobbin

2012-01-01

We herewith describe a patient with acute confusion, expressive aphasia and generalized seizures. A through workup excluded most causes of encephalopathy. He was, however, found to have TSH=18.6 MIU/ml, T3reverse=0.44nmol/L, T4=0.8ng/dl and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the patient was diagnosed with Hashimoto's encephalopathy and his mental status showed dramatic improvement (MMS 30/30) with high dose prednisone. Hashimoto's encephalopathy is rare disorder of presumed autoimmune origin characterized by cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti-Thyroid-Peroxidase AB, and a positive response to steroids. PMID:23882359

Cortical blindness and posterior reversible encephalopathy syndrome in an older patient

PubMed Central

Ait, Sabrina; Gilbert, Thomas; Cotton, Francois; Bonnefoy, Marc

2012-01-01

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity. It associates, to varying extents, neurological symptoms such as headaches, confusion, seizures and visual alterations from haemianopsia to cortical blindness. The diagnosis relies on brain MRI, showing signs of subcortical and cortical oedema in the posterior regions of the brain, with hypersignals in T2/fluid attenuated inversion recovery (FLAIR) or diffusion sequences. With early diagnosis and control of the causal factors, the symptoms and radiological signs can be – as the name implies – totally regressive. PRES can be caused by various heterogeneous factors, such as hypertension, side effect of drug therapies, eclampsia, sepsis or autoimmune diseases. The authors report here the case of an 86-year-old woman, presenting totally regressive cortical blindness and seizures, with compatible imaging. PMID:22669215

Molecular and Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (Log No. 13267017)

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (Log No. 13267017) PRINCIPAL...neuropathological findings we are currently characterizing in individuals with CTE reflect molecular and genetic differences that will enable the...INTRODUCTION: Repetitive mild traumatic brain injury leads to neurological symptoms and chronic traumatic encephalopathy (CTE). The molecular changes

Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy.

PubMed

Morichi, Shinichiro; Yamanaka, Gaku; Ishida, Yu; Oana, Shingo; Kashiwagi, Yasuyo; Kawashima, Hisashi

2014-11-01

We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types.

Approach to Clinical Syndrome of Jaundice and Encephalopathy in Tropics

PubMed Central

Anand, Anil C.; Garg, Hitendra K.

2015-01-01

A large number of patients present with jaundice and encephalopathy in tropical country like India and acute liver failure is the usual cause. Clinical presentation like ALF is also a complication of many tropical infections, and these conditions may mimic ALF but may have subtle differences from ALF. Moreover, what hepatologists see as acute liver failure in tropics is different from what is commonly described in Western Textbooks. Paracetamol overdose, which is possibly the commonest cause of ALF in UK and USA, is hardly ever seen in India. Most common etiology here is viral hepatitis (hepatitis E > hepatitis B> hepatitis A). Apart from ALF, one may also come across subacute hepatic failure (SAHF) as well as acute-on-chronic liver failure (ACLF) due to viral hepatitis. Interestingly, a host of other conditions can mimic ALF because clinical presentation in these conditions can be dominated by jaundice and encephalopathy. Malarial hepatopathy is possibly the best-known condition out of these and is not an uncommon manifestation of severe malaria. A similar presentation can also be seen in other common infections in tropics such as dengue fever, typhoid fever, leptospirosis, scrub typhus, amoebic liver abscesses, tuberculosis and other bacterial and fungal infections with or without human immunodeficiency virus (HIV) related disease. In many of these conditions, liver failure may not be underlying pathophysiology. Some pregnancy related liver diseases could also present with jaundice and encephalopathy. This review summarizes the commonly seen presentations in tropical country like India, where jaundice and encephalopathy dominate the clinical picture. PMID:26041951

Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: Linkage to convulsions and electroencephalography trait

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

Liu, A.W.; Delgado-Escueta, A.V.; Serratosa, J.M.

1995-08-01

Despite affecting 4 million Americans and 100-200 million persons worldwide, the precise molecular mechanisms of human epilepsies remain unknown. Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. In this epilepsy, electroencephalographic (EEG) 15-30 Hz multispikes produce myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Moreover, EEG 3.5-6 Hz multispike wave complexes appear in clinically asymptomatic family members. We first studied 38 members of a four-generation LA-Belize family with classical JME but with no pyknoleptic absences. Five living members had JME; four clinically asymptomatic members had EEG multispike wavemore » complexes. Pairwise analysis tightly linked microsatellites centromeric to HLA, namely D6S272 (peak lod score [Z{sub max}]=3.564-3.560 at male-female recombination [{theta}{sub m=f}]=0-0.001) and D6S257 (Z{sub max}=3.672-3.6667 at {theta}{sub m=f}=0-0.001), spanning 7 cM, to convulsive seizures and EEG multispike wave complexes. A recombination between D6S276 and D6S273 in one affected member placed the JME locus within or below HLA. Pairwise, multipoint, and recombination analyses in this large family independently proved that a JME gene is located in chromsome 6p, centromeric to HLA. We next screened, with the same chromosome 6p21.2-p11 short tandem-repeat polymorphic markers, seven multiplex pedigrees with classic JME. When lod scores for small multiplex families are added to lod scores of the LA-Belize pedigree, Z{sub max} values for D6S294 and D6S257 are >7 ({theta}{sub m=f}=0.000). Our results prove that in chromosome 6p21.2-p11 an epilepsy locus exists whose phenotype consists of classic JME with convulsions and/or EEG rapid multispike wave complexes. 31 refs., 6 figs., 4 tabs.« less

[Posterior reversible encephalopathy syndrome after neurosurgery: A literature review].

PubMed

Durán Paz, S; Moreno Casanova, I; Benatar-Haserfaty, J

2015-12-01

Posterior reversible encephalopathy syndrome is a clinical-radiological characterized by decreased level of consciousness, seizures, and visual disturbances, as well as radiologically ras brain edema, predominantly in parieto-occipital white matter regions. There are many situations that can trigger the disorder, including the administration of immunosuppressants, chemotherapy agents, hypertensive disorders, and sepsis. The case is described of a patient diagnosed with stage IV prostate adenocarcinoma, receiving chemotherapy, andundergoing a posterior reversible encephalopathy syndrome after surgery for resection of brain metastasis. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Epilepsy Surgery in Pediatric Intractable Epilepsy with Destructive Encephalopathy

PubMed Central

Park, So Young; Kwon, Hye Eun; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Dong Seok; Kim, Heung Dong

2013-01-01

Background and Purpose: The aim of the current study is to review the clinical features, surgery outcomes and parental satisfaction of children with destructive encephalopathy who underwent epilepsy surgery due to medically intractable seizures. Methods: 48 patients who underwent epilepsy surgery from October 2003 to August 2011 at Severance Children’s Hospital have been reviewed. The survey was conducted for functional outcomes and parental satisfaction at least 1 year after the surgery. Results: Epileptic encephalopathy including Lennox-Gastaut syndrome and infantile spasms was more prevalent than symptomatic focal epilepsy. Hypoxic ischemic injury accounted for most of the underlying etiology of the destructive encephalpathy, followed by central nervous system infection and head trauma. 27 patients (56.3%) underwent resective surgery and 21 patients (43.7%) underwent palliative surgery. 16 patients (33.3%) achieved seizure free and 27 parents (87.5%) reported satisfaction with the outcome of their children’s epilepsy surgery. In addition, 14 parents (77.8 %) whose children were not seizure free reported satisfaction with their children’s improvement in cognitive and behavior issues. Conclusions: Epilepsy surgery in destructive encephalopathy was effective for controlling seizures. Parents reported satisfaction not only with the surgical outcomes, but also with improvement of cognitive and behavior issues. PMID:24649473

[Ammonia as a cause for hepatic encephalopathy].

PubMed

Naimushin, Alexey; Livneh, Avi

2010-02-01

In a patient with cirrhosis of the liver, associated with hepatitis B virus, who was admitted for confusion and acute elevation of liver enzymes, a diagnosis of hepatic encephalopathy was made. A serum ammonia level of 54 (normal less than 33) microgram/liter, supported the diagnosis, but puzzled the medical staff regarding the possibility that ammonia may directly induce the confusion. While it is widely accepted that the ammonia level is a marker that usually parallels the amount of toxins and metabolites that bypasses the liver, its role in causing brain dysfunction is debated. However, since ammonia may directly hinder the metabolism of neuro-transmitters, and drugs and treatments specifically aimed at reducing ammonia levels may minimize the time interval for recovery from the acute brain insult, it is assumed that ammonia by itself had a role in bringing about the encephalopathy manifestations in our patients and other patients with cirrhosis of the liver.

OUTCOMES in CHILDHOOD FOLLOWING THERAPEUTIC HYPOTHERMIA for NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

PubMed Central

Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

2017-01-01

In this chapter we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. PMID:27863707

Non-alcoholic Korsakoff syndrome in psychiatric patients with a history of undiagnosed Wernicke's encephalopathy.

PubMed

Nikolakaros, Georgios; Ilonen, Tuula; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto

2016-11-15

Wernicke's encephalopathy is often undiagnosed, particularly in non-alcoholics. There are very few reports of non-alcoholic patients diagnosed with Korsakoff syndrome in the absence of a prior diagnosis of Wernicke's encephalopathy and no studies of diffusion tensor imaging in non-alcoholic Korsakoff syndrome. We report on three non-alcoholic psychiatric patients (all women) with long-term non-progressive memory impairment that developed after malnutrition accompanied by at least one of the three Wernicke's encephalopathy manifestations: ocular abnormalities, ataxia or unsteadiness, and an altered mental state or mild memory impairment. In neuropsychological examination, all patients had memory impairment, including intrusions. One patient had mild cerebellar vermis atrophy in MRI taken after the second episode of Wernicke's encephalopathy. The same patient had mild hypometabolism in the lateral cortex of the temporal lobes. Another patient had mild symmetrical atrophy and hypometabolism of the superior frontal lobes. Two patients were examined with diffusion tensor imaging. Reduced fractional anisotropy values were found in the corona radiata in two patients, and the uncinate fasciculus and the inferior longitudinal fasciculus in one patient. Our results suggest that non-alcoholic Korsakoff syndrome is underdiagnosed. Psychiatric patients with long-term memory impairment may have Korsakoff syndrome and, therefore, they should be evaluated for a history of previously undiagnosed Wernicke's encephalopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimizing the molecular diagnosis of CDKL5 gene-related epileptic encephalopathy in boys.

PubMed

Mei, Davide; Darra, Francesca; Barba, Carmen; Marini, Carla; Fontana, Elena; Chiti, Laura; Parrini, Elena; Dalla Bernardina, Bernardo; Guerrini, Renzo

2014-11-01

Mutations involving the cyclin-dependent kinase-like 5 (CDKL5) gene cause an early onset epileptic encephalopathy (EE) with severe neurologic impairment and a skewed 12:1 female-to-male ratio. To date, 18 mutations have been described in boys. We analyzed our cohort of boys with early onset EE to assess the diagnostic yield of our molecular approach. We studied 74 boys who presented early onset severe seizures, including infantile spasms and developmental delay, in the setting of EE, using Sanger sequencing, next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA). We identified alterations involving CDKL5 in four boys (5.4%) using NGS in one and MLPA in three. Three of four mutations were indicative of somatic mosaicism. CDKL5 gene mutations accounted for 5.4% of boys with early onset EE. Somatic mosaic mutations might be even more represented than germline mutations, probably because their less deleterious effect enhances viability of the male embryo. The molecular approach used for CDKL5 screening remarkably influences the diagnostic yield in boys. Diagnosis is optimized by Sanger sequencing combined with array-based methods or MLPA; alternatively, NGS targeted resequencing designed to also detect copy number alterations, may be performed. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Painless thyroiditis complicating with hypercalcemic encephalopathy.

PubMed

Thewjitcharoen, Yotsapon; Lumlertgul, Nuttha

2012-01-01

Severe hypercalcemia has rarely been reported in patients with hyperthyroidism. Although the pathogenesis is not clear; it is believed to be due to activation of osteoclasts resulting in excessive bone resorption. To recognize the unusual cause of hypercalcemia from painless thyroiditis, which could manifest with transient hyperthyroidism in the early stage. A 70-year-old woman presented with watery diarrhea, nausea and vomiting and significant weight loss for two months. Initially, she was misdiagnosed as having Graves'disease from her clinical presentation and thyroid function tests. Oral propylthiouracil was given to treat hyperthyroidism. However two weeks after discharge, she developed altered consciousness due to severe hypercalcemia. After combined treatment of hypercalcemia and severe hyperthyroidism, her symptoms resolved quickly. Later on, her thyroid function tests switched to subclinical hypothyroid at two months after initial presentation. No concurrent pathological conditions could be found to explain the other causes of hypercalcemia. Therefore, painless thyroiditis complicated with severe hypercalcemia was subsequently diagnosed based on her clinical course. Hypercalcemic encephalopathy is an uncommon manifestation of hyperthyroidism that should be kept in mind in patients who demonstrated clinical pictures of hyperthyroidism and alteration of consciousness. Moreover the present case emphasizes the consideration of painless thyroiditis as a differential diagnosis of hyperthyroidism because anti-thyroid medications were not indicated in this condition.

Phenytoin-induced encephalopathy in a child.

PubMed

Mehndiratta, Sumit

2016-01-01

Phenytoin is a commonly used antiepileptic medication in the pediatric age group, but it has a narrow therapeutic range. Various adverse effects have been reported commonly. We report a relatively rare case of encephalopathy in a child from overdose of injectable phenytoin due to ignorance of the previous treatment. Scrutiny of medical records and history is of utmost importance while administering such medications.

A case of recurrent encephalopathy with SCN2A missense mutation.

PubMed

Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi

2015-06-01

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.

Liver pathology in Malawian children with fatal encephalopathy

PubMed Central

Whitten, Richard; Milner, Danny A.; Yeh, Matthew M.; Kamiza, Steve; Molyneux, Malcolm E.; Taylor, Terrie E.

2010-01-01

A common clinical presentation of Plasmodium falciparum is parasitemia complicated by an encephalopathy for which other explanations cannot be found, termed cerebral malaria—an important cause of death in young children in endemic areas. Our objective was to study hepatic histopathology in Malawian children with fatal encephalopathy, with and without P falciparum parasitaemia, in order to assess the contributions of severe malaria. We report autopsy results from a series of 87 Malawian children who died between 1996 and 2008. Among 75 cases with P falciparum parasitaemia, 51 had intracerebral sequestered parasites, while 24 without sequestered parasites had other causes of death revealed by autopsy including 4 patients with clinicopathological findings which may represent Reye’s Syndrome. Hepatic histology in parasitaemic cases revealed very limited sequestration of parasites in hepatic sinusoids, even in cases with extensive sequestration elsewhere, but increased numbers of hemozoin-laden Kupffer cells were invariably present with a strong association with histological evidence of cerebral malaria by quantitative analysis. Of 12 patients who were consistently aparasitaemic during their fatal illness, 5 had clinicopathological findings which may represent Reye’s Syndrome. Hepatic sequestration of parasitized erythrocytes is not a feature of fatal malaria in Malawian children, and there is no structural damage in the liver. Reye’s syndrome may be an important cause of fatal encephalopathy in children in Malawi with and without peripheral parasitemia and warrants close scrutiny of aspirin use in malaria endemic areas. PMID:21396681

Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits.

PubMed

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; De Maria, Michela; Migliore, Michele; Migliore, Rosanna; Taglialatela, Maurizio

2015-03-04

Mutations in Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3) genes, encoding for voltage-gated K(+) channel subunits underlying the neuronal M-current, have been associated with a wide spectrum of early-onset epileptic disorders ranging from benign familial neonatal seizures to severe epileptic encephalopathies. The aim of the present work has been to investigate the molecular mechanisms of channel dysfunction caused by voltage-sensing domain mutations in Kv7.2 (R144Q, R201C, and R201H) or Kv7.3 (R230C) recently found in patients with epileptic encephalopathies and/or intellectual disability. Electrophysiological studies in mammalian cells transfected with human Kv7.2 and/or Kv7.3 cDNAs revealed that each of these four mutations stabilized the activated state of the channel, thereby producing gain-of-function effects, which are opposite to the loss-of-function effects produced by previously found mutations. Multistate structural modeling revealed that the R201 residue in Kv7.2, corresponding to R230 in Kv7.3, stabilized the resting and nearby voltage-sensing domain states by forming an intricate network of electrostatic interactions with neighboring negatively charged residues, a result also confirmed by disulfide trapping experiments. Using a realistic model of a feedforward inhibitory microcircuit in the hippocampal CA1 region, an increased excitability of pyramidal neurons was found upon incorporation of the experimentally defined parameters for mutant M-current, suggesting that changes in network interactions rather than in intrinsic cell properties may be responsible for the neuronal hyperexcitability by these gain-of-function mutations. Together, the present results suggest that gain-of-function mutations in Kv7.2/3 currents may cause human epilepsy with a severe clinical course, thus revealing a previously unexplored level of complexity in disease pathogenetic mechanisms. Copyright © 2015 the authors 0270-6474/15/353782-12$15.00/0.

Unilateral basal-ganglia involvement likely due to valproate-induced hyperammonemic encephalopathy.

PubMed

Joardar, Swarnali; Das, Shubhadeep; Chatterjee, Rita; Guha, Gautam; Hasmi, M A

2012-08-01

A male child suffering from generalized tonic clonic epilepsy, on treatment with valproate, developed fulminant hepatic failure, hyperammonemia and encephalopathy due to drug toxicity. The most extraordinary feature was his MRI (FLAIR image) of brain which showed unilateral hyperintensities in right putamen and caudate nucleus. The patient recovered on withdrawal of valproate with mild residual left sided athetotic movements during remission. Repeat investigation confirmed an improved MRI imaging and normalised blood ammonia levels. The case report is unique because of unilateral involvement of basal ganglia due to valproate-induced encephalopathy.

Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy - Kosovo Experience

PubMed Central

Zeka, Naim; Gërguri, Abdurrahim; Bejiqi, Ramush; Retkoceri, Ragip; Vuciterna, Armend

2017-01-01

BACKGROUND: West Syndrome (WS) represents as a specific epileptic encephalopathy characterised with a unique type of attacks, called infantile spasms, severe forms of abnormalities in electroencephalographic (EEG) records as a hypsarythmias and delays in the psychomotoric development. The characteristics of the disease, mostly affecting male gender, are infantile spasms and typical findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many factors in the undeveloped brain. AIM: We aimed: (1) to see the incidence of the illness and the spreading out because of gender in rapport with other syndromes in the epileptic encephalopathies group; (2) to show principles of the treatment for the illness; and (3) to present the effects of the disease in the psycho-motoric development of affected children. METHODS: The study was designed as a cross-sectional study of the patients with epileptic encephalopathies, treated in Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of December 2015. RESULTS: From the cohort group of 97 children diagnosed with epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were noted. The earliest age of disease manifestation was 74 days (± 63.8 days). On the group of children with WS, 13 of them with Natrium Valpropat were treated, with the doses of 301.9 mg (± 64.1). From the cohort group, in 89 children (91.8%) psychomotoric retardation was documented, within the higher reoccurrence in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%). CONCLUSION: WS is a frequent disease of the encephalopathies with the epileptogenic framework. The resistance in anticonvulsive therapy is huge, and psychomotoric retardation follows a big percentage of children with this syndrome. PMID:29362620

Frequent occurrence of therapeutically reversible CMV-associated encephalopathy during radiotherapy of the brain.

PubMed

Goerig, Nicole L; Frey, Benjamin; Korn, Klaus; Fleckenstein, Bernhard; Überla, Klaus; Schmidt, Manuel A; Dörfler, Arnd; Engelhorn, Tobias; Eyüpoglu, Ilker; Rühle, Paul F; Putz, Florian; Semrau, Sabine; Gaipl, Udo S; Fietkau, Rainer

2016-12-01

Neurological decline during radio(chemo)therapy of the brain is often attributed to disease progression or side effects of radiotherapy. Diagnosis of opportunistic neurotropic infections such as cytomegalovirus (CMV) infections is uncommon, even though high-grade gliomas and some brain metastases are known to contain CMV particles. We prospectively examined the frequency of CMV encephalopathy during radiotherapy of the brain. Fifty patients requiring whole-brain radiotherapy for brain metastases (n = 27) or local radio(chemo)therapy of the brain for high-grade gliomas (n = 23) were observed in the prospective observational GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Thirty-two of 50 (64%) patients were positive for anti-CMV IgG before radio(chemo)therapy. Fifteen of those 32 (48%) developed viremia during or up to 28 days after treatment. Thirteen of those 15 (87%) required treatment for CMV-associated encephalopathy. MRIs were negative for disease progression, edema, or bleeding. None of the patients negative for anti-CMV IgG developed viremia, suggesting a reactivation rather than a primary infection.In the group at risk consisting of anti-CMV IgG+ patients, age >65 (P = .004) and the amount of dexamethasone taken during radio(chemo)therapy (P = .004) were associated with an increased risk for CMV-associated encephalopathy. One hundred and fifty days after the start of radio(chemo)therapy, survival was 74% (14/19) (no encephalopathy) versus 54% (7/13) (encephalopathy) (odds ratio, 0.42; 95% CI, 0.03-1.86; P = .25). CMV reactivation frequently causes encephalopathy during radio(chemo)therapy of the brain. The unexpected high incidence of this infection makes it highly clinically relevant for every treating physician. © The Author(s) 2016

Granulomatous herpes simplex encephalitis in an infant with multicystic encephalopathy: a distinct clinicopathologic entity?

PubMed

Schutz, Peter W; Fauth, Clarissa T; Al-Rawahi, Ghada N; Pugash, Denise; White, Valerie A; Stockler, Sylvia; Dunham, Christopher P

2014-04-01

Herpes simplex virus encephalitis can manifest as a range of clinical presentations including classic adult, neonatal, and biphasic chronic-granulomatous herpes encephalitis. We report an infant with granulomatous herpes simplex virus type 2 encephalitis with a subacute course and multicystic encephalopathy. A 2-month-old girl presented with lethargy and hypothermia. Computed tomography scan of the head showed multicystic encephalopathy and calcifications. Cerebrospinal fluid analysis by polymerase chain reaction testing for herpes simplex virus 1 and 2, enterovirus, and cytomegalovirus was negative. Normal cerebrospinal fluid interferon-α levels argued against Aicardi-Goutières syndrome. The patient died 2 weeks after presentation. At autopsy, multicystic encephalopathy was confirmed with bilateral gliosis, granulomatous inflammation with multinucleated giant cells, and calcifications. Bilateral healing necrotizing retinitis suggested a viral etiology, but retina and brain were free of viral inclusions and immunohistochemically negative for herpes simplex virus-2 and cytomegalovirus. However, polymerase chain reaction analysis showed herpes simplex virus-2 DNA in four cerebral paraffin blocks. Subsequent repeat testing of the initial cerebrospinal fluid sample using a different polymerase chain reaction assay was weakly positive for herpes simplex virus-2 DNA. Granulomatous herpes simplex virus encephalitis in infants can present with subacute course and result in multicystic encephalopathy with mineralization and minimal cerebrospinal fluid herpes simplex virus DNA load. Infectious etiologies should be carefully investigated in the differential diagnosis of multicystic encephalopathy with mineralization, in particular if multinucleated giant cells are present. Copyright © 2014 Elsevier Inc. All rights reserved.

Childhood outcomes after hypothermia for neonatal encephalopathy.

PubMed

Shankaran, Seetha; Pappas, Athina; McDonald, Scott A; Vohr, Betty R; Hintz, Susan R; Yolton, Kimberly; Gustafson, Kathryn E; Leach, Theresa M; Green, Charles; Bara, Rebecca; Petrie Huitema, Carolyn M; Ehrenkranz, Richard A; Tyson, Jon E; Das, Abhik; Hammond, Jane; Peralta-Carcelen, Myriam; Evans, Patricia W; Heyne, Roy J; Wilson-Costello, Deanne E; Vaucher, Yvonne E; Bauer, Charles R; Dusick, Anna M; Adams-Chapman, Ira; Goldstein, Ricki F; Guillet, Ronnie; Papile, Lu-Ann; Higgins, Rosemary D

2012-05-31

We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available. In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70. Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80). The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of

Prevalence, severity and early outcomes of hypoxic ischemic encephalopathy among newborns at a tertiary hospital, in northern Tanzania.

PubMed

Simiyu, Irene N; Mchaile, Deborah N; Katsongeri, Kahindo; Philemon, Rune N; Msuya, Sia E

2017-05-25

Hypoxic Ischemic Encephalopathy (HIE) remains a problem of great concern worldwide especially in developing countries. The occurrence of a neurological syndrome can be an indicator of insult to the brain. We aimed to determine the prevalence, HIE proportions, neurological signs and early outcomes of newborns that developed birth asphyxia at KCMC Tanzania. A prospective study was conducted at KCMC from November 2014 to April 2015 among newborns with birth asphyxia. Sarnat and Sarnat score was used to assess newborns immediately after birth to classify HIE and were later followed daily for 7 days or until discharge. Of the 1752 deliveries during the study period, 11.5% (n = 201) had birth asphyxia. Of the 201 newborns, 187 had HIE. Of these 187 with HIE; 39.0% had moderate HIE and 10.2% had severe HIE according to the Sarnat and Sarnat classification. Neurological signs that were observed during the study period were; weak/absent reflexes (46.0%), hypotonia (43.3%) and lethargy (42.2%). Mortality was 9.1% among the 187 newborns with HIE. Mortality was higher among newborns with severe HIE 84.2% (16/19) compared to those with moderate HIE 1.4% (1/73). On the 7th day after delivery, 17.1% (32/187) of the newborns did not show any change from the initial score at delivery. Prevalence of birth asphyxia is high in our setting and most of the newborns (49%) end up with moderate/severe HIE. Good obstetric care and immediate resuscitation of newborns are vital in reducing the occurrence of HIE and improving the general outcome of newborns.

Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy.

PubMed

Flex, Elisabetta; Niceta, Marcello; Cecchetti, Serena; Thiffault, Isabelle; Au, Margaret G; Capuano, Alessandro; Piermarini, Emanuela; Ivanova, Anna A; Francis, Joshua W; Chillemi, Giovanni; Chandramouli, Balasubramanian; Carpentieri, Giovanna; Haaxma, Charlotte A; Ciolfi, Andrea; Pizzi, Simone; Douglas, Ganka V; Levine, Kara; Sferra, Antonella; Dentici, Maria Lisa; Pfundt, Rolph R; Le Pichon, Jean-Baptiste; Farrow, Emily; Baas, Frank; Piemonte, Fiorella; Dallapiccola, Bruno; Graham, John M; Saunders, Carol J; Bertini, Enrico; Kahn, Richard A; Koolen, David A; Tartaglia, Marco

2016-10-06

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective β-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/β-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with

Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE).

PubMed

Natarajan, Girija; Pappas, Athina; Shankaran, Seetha

2016-12-01

In this article, we review the childhood outcomes of neonates with birth depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children prior to the era of hypothermia for neuroprotection will first be summarized, followed by discussion of results from randomized controlled trials of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The predictors of outcome in childhood following neonatal HIE using clinical and imaging biomarkers following hypothermia therapy will be described. Copyright © 2016 Elsevier Inc. All rights reserved.

Hippocampal metabolic dysfunction in juvenile myoclonic epilepsy: 3D multivoxel spectroscopy study.

PubMed

Ristić, Aleksandar J; Ostojić, Jelena; Kozić, Duško; Vojvodić, Nikola M; Popović, Ljubica M; Janković, Slavko; Baščarević, Vladimir; Sokić, Dragoslav V

2011-06-15

To investigate the metabolic differences in hippocampi of patients with juvenile myoclonic epilepsy (JME) and healthy controls using magnetic resonance spectroscopy (MRS). A 3D multivoxel SE 135 MRS study on 1.5 T scanner of both hippocampi was performed in 17 patients with JME and normal brain MRI and in 19 age and sex matched controls. Three dominant signals were measured: Choline (Cho), Creatine (tCr) and N-Acetylaspartate (NAA) and expressed as ratios of Cho:tCr, NAA:tCr, NAA:Cho and NAA:(Cho+tCr). Metabolite ratios in head, body and tail of each hippocampus in the JME group of patients were compared with ratios from corresponding structures in the control group. We found a significant difference in metabolite ratios of both hippocampi between the JME and the control groups. We detected significant differences of Cho:tCr in the head, NAA:tCr in the head, body and tail, NAA:Cho and NAA:(Cho+tCr) in the body and tail of the left hippocampus, and NAA:Cho and NAA:(Cho+tCr) in the body and tail of the right hippocampus. Although not previously recognized as a part of the epileptogenic network, our results suggest that the hippocampus, well recognized as a key player in focal epilepsies, may have a certain role in the pathogenesis of JME. Copyright © 2010. Published by Elsevier B.V.

An unusual autopsy case of cytokine storm-derived influenza-associated encephalopathy without typical histopathological findings: autopsy case report.

PubMed

Nara, Akina; Nagai, Hisashi; Yamaguchi, Rutsuko; Yoshida, Ken-ichi; Iwase, Hirotaro; Mizuguchi, Masashi

2015-03-01

Cytokine storm-derived influenza-associated encephalopathy is a severe complication, affecting not only the brain but also multiple systemic organs including the heart and lungs. Hundreds of Japanese children are afflicted by influenza-associated encephalopathy every year. Influenza-associated encephalopathy can be diagnosed by pathological changes, such as advanced brain edema and disruption of astrocytic projections, which is known as clasmatodendrosis. In the present case, despite the absence of significant histopathological findings in the brain, the diagnosis of influenza-associated encephalopathy was made on the basis of autopsy findings such as brain swelling, pathological findings including diffuse alveolar damage, and increase in the concentrations of interleukin-6 in both the serum and cerebrospinal fluid. In this case, the interval from high fever to death was approximately 7 hours and may have been too short for histopathological features to develop. This is an unusual autopsy case of cytokine storm-derived influenza-associated encephalopathy without typical histopathological findings.

Hyperammonemic Encephalopathy Associated With Fibrolamellar Hepatocellular Carcinoma: Case Report, Literature Review, and Proposed Treatment Algorithm.

PubMed

Chapuy, Claudia I; Sahai, Inderneel; Sharma, Rohit; Zhu, Andrew X; Kozyreva, Olga N

2016-04-01

We report a case of a 31-year-old man with metastatic fibrolamellar hepatocellular carcinoma (FLHCC) treated with gemcitabine and oxaliplatin complicated by hyperammonemic encephalopathy biochemically consistent with acquired ornithine transcarbamylase deficiency. Awareness of FLHCC-associated hyperammonemic encephalopathy and a pathophysiology-based management approach can optimize patient outcome and prevent serious complications. A discussion of the management, literature review, and proposed treatment algorithm of this rare metabolic complication are presented. Pathophysiology-guided management of cancer-associated hyperammonemic encephalopathy can improve patient outcome and prevent life-threatening complications. Community and academic oncologists should be aware of this serious metabolic complication of cancer and be familiar with its management. ©AlphaMed Press.

Post-ivermectin encephalopathy in Senegal: a case report.

PubMed

Massi, Daniel Gams; Mansare, Mohamed Lelouma; Traoré, Mariétou; Ndiaye, Moustapha; Diop, Amadou Gallo; Ndiaye, Mouhamadou Mansour

2017-01-01

Ivermectin is an ant parasitic drug used for combating onchocerciasis and lymphatic filariasis. It works by inhibiting the function of neurons and muscles, thus causing paralysis of microfilariae. Side effects of this drug have been reported including post-ivermectin encephalopathy requiring emergency care in hospital. We report the case of a 35 years old patient living in rural areas of Senegal who presented two days after a mistake in administration of a second dose of ivermectin, headaches, altered consciousness and bilateral blindness. The workup revealed brain white matter lesions, abnormal liver function tests and biological inflammation without evidence of Loa loa microfilariae in blood and cerebrospinal fluid. Corticosteroid treatment was administered in emergency and patient recovered despite the persistence of bilateral blindness. Inflammatory process seems to have an important role in the pathophysiology of this encephalopathy. We should therefore carefully control the administration of this drugs.

Preliminary report of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) score.

PubMed

Baskin-Bey, Edwina S; Stewart, Charmaine A; Mitchell, Mary M; Bida, John P; Rosenthal, Theodore J; Nyberg, Scott L

2008-01-01

Audiovisual simulations of real-life driving (ie, driving simulators) have been used to assess neurologic dysfunction in a variety of medical applications. However, the use of simulated driving to assess neurologic impairment in the setting of liver disease (ie, hepatic encephalopathy) is limited. The aim of this analysis was to develop a scoring system based on simulated driving performance to assess mild cognitive impairment in cirrhotic patients with hepatic encephalopathy. This preliminary analysis was conducted as part of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) pilot study. Cirrhotic volunteers initially underwent a battery of neuropsychological tests to identify those cirrhotic patients with mild cognitive impairment. Performance during an audiovisually simulated course of on-road driving was then compared between mildly impaired cirrhotic patients and healthy volunteers. A scoring system was developed to quantify the likelihood of cognitive impairment on the basis of data from the simulated on-road driving. Mildly impaired cirrhotic patients performed below the level of healthy volunteers on the driving simulator. Univariate logistic regression and correlation models indicated that several driving simulator variables were significant predictors of cognitive impairment. Five variables (run time, total map performance, number of collisions, visual divided attention response, and average lane position) were incorporated into a quantitative model, the HEADS scoring system. The HEADS score (0-9 points) showed a strong correlation with cognitive impairment as measured by area under the receiver-operator curve (.89). The HEADS system appears to be a promising new tool for the assessment of mild hepatic encephalopathy.

[Prognostic factors after cardiac arrest. Usefulness of early video-electroencephalogram].

PubMed

Arméstar, Fernando; Becerra Cuñat, Juan Luis; León Chan, Yariela; Mesalles Sanjuan, Eduard; Moreno, José Antonio; Jiménez González, Marta; Roca, Josep

2015-05-08

Predictors of unfavorable outcome in patients after cardiopulmonary arrest (CPA) are important to make decisions about the limitation of therapeutic efforts. The aim was to analyze the clinical variables in the prognosis of patients recovered after CPA. Retrospective study on comatose patients with recovered CPA. The variables were: age, sex, Glasgow Coma Score (GCS), pupillary light reflex, other variables related to CPA (cause, duration, witnessed or not witnessed), myoclonic status and electroencephalographic (EEG) patterns. Fifty patients were studied. The variables associated with mortality were the absence of pupillary light reflex (hazard ratio [HR] 0.277, 95% confidence interval [95% CI] 0.103-0.741, P=.01), a low GCS (HR 0.701, 95% CI 0.542-0.908, P=.007) and myoclonic state (HR 0.38, 95% CI 0.176-0.854, P=.01). We evaluated the EEG patterns in 22 patients. No statistical significance was observed. The absence of pupillary light reflex, a low GCS and myoclonic state are prognostic factors in patients recovered after a CPA. The EEG patterns showed a nonsignificant association with prognosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus

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

Nijs, Laurence de; Lakaye, Bernard; Coumans, Bernard

2006-09-10

A novel gene, EFHC1, mutated in juvenile myoclonic epilepsy (JME) encodes a protein with three DM10 domains of unknown function and one putative EF-hand motif. To study the properties of EFHC1, we expressed EGFP-tagged protein in various cell lines. In interphase cells, the fusion protein was present in the cytoplasm and in the nucleus with specific accumulation at the centrosome. During mitosis EGFP-EFHC1 colocalized with the mitotic spindle, especially at spindle poles and with the midbody during cytokinesis. Using a specific antibody, we demonstrated the same distribution of the endogenous protein. Deletion analyses revealed that the N-terminal region of EFHC1more » is crucial for the association with the mitotic spindle and the midbody. Our results suggest that EFHC1 could play an important role during cell division.« less

Hepatic encephalopathy secondary to a splenorenal shunt that manifested a long time after a liver transplantation.

PubMed

Tomás Pujante, Paula; Jiménez Sánchez, Andrés Francisco; Iglesias Jorquera, Elena; Pons Miñano, José Antonio

2018-04-24

Splenorenal shunts are a rare cause of hyperammonemia and hepatic encephalopathy in the absence of cirrhosis. We report the case of a woman, who presented hepatic encephalopathy, with a normal functioning graft, after 14 years of liver transplantation, confirmed by liver biopsy.

Metronidazole-induced encephalopathy: not always a reversible situation.

PubMed

Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna

2015-06-01

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.

[Value of early-stage cerebral oxygen utilization coefficient in predicting delayed encephalopathy after acute carbon monoxide poisoning].

PubMed

Liu, Q; Li, W; Li, N; Xiao, Q M; He, J Q; Wang, W Z; Qi, H N; Wang, P

2017-05-20

Objective: To investigate the dynamic change in cerebral oxygen utilization coefficient (O(2)UCc) in the early stage of acute severe carbon monoxide poisoning (ASCMP) and its value in predicting delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) . Methods: A prospective observational study was conducted for patients with ASCMP who were admitted to our hospital from November 2013 to March 2016, and their baseline features and physiological parameters were recorded. Observation ended at two months after acute poisoning; according to the presence or absence of DEACMP, the patients were divided into DEACMP group with 21 patients and non-DEACMP group with 64 patients. The change in O(2)UCc was monitored on admission and at 6, 24, 48, and 72 hours. Spearman correlation was used to investigate the correlation between O(2)UCc and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of O(2)UCc in predicting DEACMP. Results: Both groups had a significant increase in O(2)UCc on admission, and the DEACMP group had a significantly greater increase than the non-DEACMP group (52.57%±9.30% vs 41.46±%6.37%, P <0.05) . Then both groups tended to have a reduction in O(2)UCc, and the DEACMP group had a significantly higher O(2)UCc than the non-DEACMP group at 6, 24, and 48 hours (47.40%±7.92%, 39.38%±8.01%, and 32.29%±6.31% vs 34.51%±7.89%, 28.79%±5.4%, and 27.72%±5.46%, P <0.05) . On admission and at 6, 24, and 48 hours, O2UCc was positively correlated with APACHE II score ( r =0.304, 0.398, 0.426, and 0.300, P =0.005, 0.000, 0.000, and 0.005) . The ROC curve showed that O(2)UCc had a value in predicting DEACMP on admission and at 6, 24, and 48 hours, and 6-hour O2UCc had the highest predictive value with an area under the ROC curve of 0.870 (95% confidence interval 0.794-0.947, P <0.05) . Conclusion: The dynamic change in O(2)UCc has a reference value in

Acute Necrotizing Encephalopathy: An Underrecognized Clinicoradiologic Disorder

PubMed Central

Wu, Xiujuan; Wu, Wei; Pan, Wei; Wu, Limin; Liu, Kangding; Zhang, Hong-Liang

2015-01-01

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

Accumulation of Mutant Neuroserpin Precedes Development of Clinical Symptoms in Familial Encephalopathy with Neuroserpin Inclusion Bodies

PubMed Central

Galliciotti, Giovanna; Glatzel, Markus; Kinter, Jochen; Kozlov, Serguei V.; Cinelli, Paolo; Rülicke, Thomas; Sonderegger, Peter

2007-01-01

Intracellular protein deposition due to aggregation caused by conformational alteration is the hallmark of a number of neurodegenerative disorders, including Parkinson’s disease, tauopathies, Huntington’s disease, and familial encephalopathy with neuroserpin inclusion bodies. The latter is an autosomal dominant disorder caused by point mutations in neuroserpin resulting in its destabilization. Mutant neuroserpin polymerizes and forms intracellular aggregates that eventually lead to neurodegeneration. We generated genetically modified mice expressing the late-onset S49P-Syracuse or the early-onset S52R-Portland mutation of neuroserpin in central nervous system neurons. Mice exhibited morphological, biochemical, and clinical features resembling those found in the human disease. Analysis of brains revealed large intraneuronal inclusions composed exclusively of mutant neuroserpin, accumulating long before the development of clinical symptoms in a time-dependent manner. Clinical symptoms and amount of neuroserpin inclusions correlated with the predicted instability of the protein. The presence of inclusion bodies in subclinical mice indicates that in humans the prevalence of the disease could be higher than anticipated. In addition to shedding light on the pathophysiology of the human disorder, these mice provide an excellent model to study mechanisms of neurodegeneration or establish novel therapies for familial encephalopathy with neuroserpin inclusion bodies and other neurodegenerative diseases with intracellular protein deposition. PMID:17392169

Encephalopathy Associated with Influenza B in a Healthy Young Man.

PubMed

Shimamoto, Masaki; Okada, Satoshi; Terashima, Takeshi

2017-01-01

A 19-year-old man presented with a fever, convulsions, and loss of consciousness at our hospital. The patient had a Glasgow Coma Scale score of 12. Influenza B virus infection was diagnosed using the rapid test kit, and an eight-fold increase in the serum levels of anti-influenza B virus antibody was confirmed using the complement fixation test. Brain magnetic resonance imaging showed multifocal high-signal lesions, and an electroencephalogram showed diffuse slowing of the background activity, indicating acute encephalopathy. After treatment with peramivir and methylprednisolone for 3 days, the patient was discharged without any neurological impairment. This was a case of influenza B infection associated with acute encephalopathy in a healthy young man.

Refeeding encephalopathy in a patient with severe hypophosphataemia and hyperammonaemia.

PubMed

Becker, S; Dam, G; Hvas, C L

2015-02-01

The refeeding syndrome is a potentially fatal condition that affects multiple organ systems. It is the consequence of fluid and electrolyte shifts that may occur in a malnourished patient following the introduction of nutrition therapy. The most prominent characteristic is hypophosphataemia. Although hyperammonaemia is usually seen in decompensated liver cirrhosis or acute liver failure, it may occur in other settings. We report a clinical case of prolonged and severe encephalopathy accompanied by hypophosphataemia and hyperammonaemia in a 59-year-old woman with no preexisting liver disease, urea cycle defects or portosystemic shunting. We suggest that these biochemical abnormalities were caused by uncontrolled refeeding and that the clinical picture was consistent with refeeding encephalopathy.

Transmissible Spongiform Encephalopathy and Meat Safety

NASA Astrophysics Data System (ADS)

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.

A Proposed Physiopathological Pathway to Hyperammonemic Encephalopathy in a Non-Cirrhotic Patient with Fibrolamellar Hepatocellular Carcinoma without Ornithine Transcarbamylase (OTC) Mutation.

PubMed

Surjan, Rodrigo C; Dos Santos, Elizabeth S; Basseres, Tiago; Makdissi, Fabio F; Machado, Marcel A

2017-03-08

BACKGROUND Hyperammonemic encephalopathy is a potentially fatal condition that may progress to irreversible neuronal damage and is usually associated with liver failure or portosystemic shunting. However, other less common conditions can lead to hyperammonemia in adults, such as fibrolamellar hepatocellular carcinoma. Clinical awareness of hyperammonemic encephalopathy in patients with normal liver function is paramount to timely diagnosis, but understanding the underlying physiopathology is decisive to initiate adequate treatment for complete recovery. CASE REPORT A 31-year-old male with fibrolamellar carcinoma and peritoneal carcinomatosis presented with rapid onset hyperammonemic encephalopathy. Despite usual treatment for hepatic encephalopathy, his hyperammonemia was aggravated. A physiopathological pathway to encephalopathy resulting from hepatocellular dysfunction or portosystemic shunting was suspected and proper treatment was initiated, which resulted in complete remission of encephalopathy. Thus, we propose there is a physiopathology path to hyperammonemic encephalopathy in non-cirrhotic patients with fibrolamellar carcinoma independent of ornithine transcarbamylase (OTC) mutation. An ornithine metabolism imbalance resulting from overexpression of Aurora Kinase A as a result of a single, recurrent heterozygous deletion on chromosome 19, common to all fibrolamellar carcinomas, can lead to a c-Myc and ornithine decarboxylase overexpression that results in ornithine transcarboxylase dysfunction with urea cycle disorder and subsequent hyperammonemia. CONCLUSIONS The identification of a physiopathological pathway allowed adequate medical treatment and full patient recovery from severe hyperammonemic encephalopathy.

Low Apgar score, neonatal encephalopathy and epidural analgesia during labour: a Swedish registry-based study.

PubMed

Törnell, S; Ekéus, C; Hultin, M; Håkansson, S; Thunberg, J; Högberg, U

2015-04-01

Maternal intrapartum fever (MF) is associated with neonatal sequelae, and women in labour who receive epidural analgesia (EA) are more likely to develop hyperthermia. The aims of this study were to investigate if EA and/or a diagnosis of MF were associated to adverse neonatal outcomes at a population level. Population-based register study with data from the Swedish Birth Register and the Swedish National Patient Register, including all nulliparae (n=294,329) with singleton pregnancies who gave birth at term in Sweden 1999-2008. Neonatal outcomes analysed were Apgar score (AS)<7 at 5 min and ICD-10 diagnosis of neonatal encephalopathy (e.g. convulsions or neonatal cerebral ischaemia). Multivariate logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals (CI). EA was used in 44% of the deliveries. Low AS or encephalopathy was found in 1.26% and 0.39% of the children in the EA group compared with 0.80% and 0.29% in the control group. In multivariate analysis, EA was associated with increased risk with low AS, AOR 1.27 (95% CI 1.16-1.39), but not with diagnosis of encephalopathy, 1.11 (0.96-1.29). A diagnosis of MF was associated with increased risk for both low AS, 2.27 (1.71-3.02), and of neonatal encephalopathy, 1.97 (1.19-3.26). Diagnosis of MF was associated with low AS and neonatal encephalopathy, whereas EA was only associated with low AS and not with neonatal encephalopathy. The found associations might be a result of confounding by indication, which is difficult to assess in a registry-based population study. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Wernicke's encephalopathy after cardiac surgery.

PubMed

Nishimura, Yoshiyuki

2018-05-01

A 76-year-old woman who had been on hemodialysis for 3 years developed ischemic mitral valve insufficiency, tricuspid insufficiency, and chronic atrial fibrillation, and underwent cardiac surgery. On the 4th postoperative day, she experienced a sudden disturbance of consciousness, aphasia, and limb ataxia. Brain computed tomography and magnetic resonance imaging showed no abnormalities. Wernicke's encephalopathy was suspected and the patient was given vitamin B1, whereupon her symptoms gradually improved. On the 42nd postoperative day, she was free of neurological symptoms and discharged.

Laboratory activities involving transmissible spongiform encephalopathy causing agents

PubMed Central

Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

2013-01-01

Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis

PubMed Central

Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

2015-01-01

A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection. PMID:25596288

Use of Murine Bioassay to Resolve Ovine Transmissible Spongiform Encephalopathy Cases Showing a Bovine Spongiform Encephalopathy Molecular Profile

PubMed Central

Beck, Katy E; Sallis, Rosemary E; Lockey, Richard; Vickery, Christopher M; Béringue, Vincent; Laude, Hubert; Holder, Thomas M; Thorne, Leigh; Terry, Linda A; Tout, Anna C; Jayasena, Dhanushka; Griffiths, Peter C; Cawthraw, Saira; Ellis, Richard; Balkema-Buschmann, Anne; Groschup, Martin H; Simmons, Marion M; Spiropoulos, John

2012-01-01

Two cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild-type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and subpassage, incubation period (IP) of disease, PrPSc immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterize the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by the following: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild-type mice; PrPSc deposition pattern in wild-type mice; and IP and Western blot data in transgenic mice. Furthermore, immunohistochemistry (IHC) revealed that each case generated two distinct PrPSc deposition patterns in both wild-type and transgenic mice, suggesting that two scrapie strains coexisted in the ovine hosts. Critically, these data confirmed the original differential IHC categorization that these UK-1 and UK-2 cases were not compatible with BSE. PMID:21919992

Hepatic encephalopathy

PubMed Central

2017-01-01

Abstract Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver diseases. The precise pathophysiology of HE is still under discussion; the leading hypothesis focus on the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests. Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis. HE is classified according to the underlying disease, the severity of manifestations, its time course and the existence of precipitating factors. Treatment of overt HE includes supportive therapies, treatment of precipitating factors, lactulose and/or rifaximin. Routine treatment for minimal HE is only recommended for selected patients. PMID:28533911

Short and long-term outcomes in children with suspected acute encephalopathy.

PubMed

Nishiyama, Masahiro; Nagase, Hiroaki; Tanaka, Tsukasa; Fujita, Kyoko; Kusumoto, Mayumi; Kajihara, Shinsuke; Yamaguchi, Yoshimichi; Maruyama, Azusa; Takeda, Hiroki; Uetani, Yoshiyuki; Tomioka, Kazumi; Toyoshima, Daisaku; Taniguchi-Ikeda, Mariko; Morioka, Ichiro; Takada, Satoshi; Iijima, Kazumoto

2016-09-01

The time-dependent changes that occur in children after acute encephalopathy are not clearly understood. Therefore, we assessed changes in brain function after suspected acute encephalopathy over time. We created a database of children admitted to the pediatric intensive care unit at Kobe Children's Hospital because of convulsions or impaired consciousness with fever between 2002 and 2013. Clinical courses and outcomes were reviewed and patients who met the following criteria were included in the study: (1) 6months to 15years of age, (2) no neurological abnormality before onset, (3) treated for suspected acute encephalopathy, and (4) followed after 1 (0-2) month and 12 (10-17) months of onset. Outcomes were assessed using the Pediatric Cerebral Performance Category (PCPC) scale, with a score of 1 representing normal performance; 2, mild disability; 3, moderate disability; 4, severe disability; 5, vegetative state; and 6, brain death. A total of 78 children (32 male) with a median (range) age at onset of 20 (6-172) months were enrolled. Fifty-one cases scored 1 on the PCPC, 13 scored 2, three scored 3, five scored 4, one scored 5, and five cases scored 6 at discharge. Whereas seven of the 13 cases that scored a 2 on the PCPC recovered normal brain function after 12months, none of the nine cases that scored a 3-5 on the PCPC recovered normal function. Our findings suggest moderate to severe disability caused by acute encephalopathy had lasting consequences on brain function, whereas mild disability might result in improved function. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Acute encephalitis and encephalopathy associated with human parvovirus B19 infection in children.

PubMed

Watanabe, Toru; Kawashima, Hideshi

2015-11-08

Reports of neurologic manifestations of human parvovirus B19 (B19) infection have been on the rise. Acute encephalitis and encephalopathy is the most common, accounting for 38.8% of total B19-associated neurological manifestations. To date, 34 children with B19 encephalitis and encephalopathy have been reported, which includes 21 encephalitis and 13 encephalopathy cases. Ten (29%) were immunocompromised and 17 (39%) had underlying diseases. Fever at the onset of disease and rash presented in 44.1% and 20.6% of patients, respectively. Neurological manifestations include alteration of consciousness occurred in all patients, seizures in 15 (44.1%) patients, and focal neurologic signs in 12 (35.3%) patients. Anemia and pleocytosis in cerebrospinal fluid (CSF) occurred in 56.3% and 48.1% of patients, respectively. Serum Anti-B19 IgM (82.6%) and CSF B19 DNA (90%) were positive in the majority of cases. Some patients were treated with intravenous immunoglobulins and/or steroids, although an accurate evaluation of the efficacy of these treatment modalities cannot be determined. Nineteen (57.6%) patients recovered completely, 11 (33.3%) patients had some neurological sequelae and 3 (8.8%) patients died. Although the precise pathogenesis underlying the development of B19 encephalitis and encephalopathy is unclear, direct B19 infection or NS1protein of B19 toxicity in the brain, and immune-mediated brain injuries have been proposed.

Deep cerebral venous thrombosis mimicking influenza-associated acute necrotizing encephalopathy: a case report.

PubMed

Taniguchi, Daisuke; Nakajima, Sho; Hayashida, Arisa; Kuroki, Takuma; Eguchi, Hiroto; Machida, Yutaka; Hattori, Nobutaka; Miwa, Hideto

2017-09-26

Acute necrotizing encephalopathy is one of the most devastating neurological complications of influenza virus infection. Acute necrotizing encephalopathy preferentially affects the thalamus bilaterally, as does deep cerebral venous thrombosis, which can lead to misdiagnosis. A 52-year-old Japanese woman infected with seasonal influenza B virus presented to the emergency care unit in our hospital with progressive alteration of her level of consciousness. Bilateral thalamic lesions were demonstrated by magnetic resonance imaging, leading to a tentative diagnosis of acute necrotizing encephalopathy. However, she had deep cerebral venous thrombosis, and the presence of diminished signal and enlargement of deep cerebral veins on T2*-weighted imaging contributed to a revised diagnosis of deep cerebral venous thrombosis. Anticoagulant therapy was initiated, leading to her gradual recovery, with recanalization of the deep venous system and straight sinus. To the best of our knowledge, these results represent the first report of deep cerebral venous thrombosis associated with influenza infection. It is clinically important to recognize that deep cerebral venous thrombosis, although rare, might be one of the neurological complications of influenza infection. In the presence of bilateral thalamic lesions in patients with influenza infection, deep cerebral venous thrombosis should be considered in addition to acute necrotizing encephalopathy. Delays in diagnosis and commencement of anticoagulant therapy can lead to unfavorable outcomes.

[Role of rifaximin in the treatment of hepatic encephalopathy].

PubMed

Sanchez-Delgado, Jordi; Miquel, Mireia

2016-04-01

Hepatic encephalopathy (HE) is a frequent and serious complication of liver cirrhosis. In addition to correction of the precipitating factors, the most commonly used treatments are non-absorbable disaccharides and rifaximin. Many of the recommendations are based on current clinical practice and there are few randomized controlled trials. Currently, rifaximin should be initiated during an episode of EH if, after 24-48 hours of non-absorbable disaccharide therapy, there is no clinical improvement. In recurrent EH, it is advisable to add rifaximin in patients under non-absorbable disaccharide therapy who develop a new episode. Currently, standard treatment with rifaximin for minimal EH is not recommended. Rifaximin is effective in the acute treatment of overt encephalopathy and in preventing recurrence. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Hepatic Encephalopathy: From the Pathogenesis to the New Treatments

PubMed Central

Cordoba, Juan

2014-01-01

Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE. PMID:27335836

Imaging in Chronic Traumatic Encephalopathy and Traumatic Brain Injury

PubMed Central

Shetty, Teena; Raince, Avtar; Manning, Erin; Tsiouris, Apostolos John

2016-01-01

Context: The diagnosis of chronic traumatic encephalopathy (CTE) can only be made pathologically, and there is no concordance of defined clinical criteria for premorbid diagnosis. The absence of established criteria and the insufficient imaging findings to detect this disease in a living athlete are of growing concern. Evidence Acquisition: The article is a review of the current literature on CTE. Databases searched include Medline, PubMed, JAMA evidence, and evidence-based medicine guidelines Cochrane Library, Hospital for Special Surgery, and Cornell Library databases. Study Design: Clinical review. Level of Evidence: Level 4. Results: Chronic traumatic encephalopathy cannot be diagnosed on imaging. Examples of imaging findings in common types of head trauma are discussed. Conclusion: Further study is necessary to correlate the clinical and imaging findings of repetitive head injuries with the pathologic diagnosis of CTE. PMID:26733590

Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests).

PubMed

Kappus, Matthew R; Bajaj, Jasmohan S

2012-02-01

Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise. Copyright © 2012 Elsevier Inc. All rights reserved.

Intravenous Poison Hemlock Injection Resulting in Prolonged Respiratory Failure and Encephalopathy.

PubMed

Brtalik, Douglas; Stopyra, Jason; Hannum, Jennifer

2017-06-01

Poison hemlock (Conium maculatum) is a common plant with a significant toxicity. Data on this toxicity is sparse as there have been few case reports and never a documented poisoning after intravenous injection. We present a case of intravenous poison hemlock injection encountered in the emergency department. We describe a 30-year-old male who presented to the emergency department after a brief cardiac arrest after injecting poison hemlock. The patient had return of spontaneous circulation in the emergency department but had prolonged muscular weakness and encephalopathy later requiring tracheostomy. Intravenous injection of poison hemlock alkaloids can result in significant toxicity, including cardiopulmonary arrest, prolonged weakness, and encephalopathy.

Contributory factors and potentially avoidable neonatal encephalopathy associated with perinatal asphyxia.

PubMed

Sadler, Lynn C; Farquhar, Cynthia M; Masson, Vicki L; Battin, Malcolm R

2016-06-01

The recently published monograph, Neonatal encephalopathy and neurologic outcome, from the American College of Obstetricians and Gynecologists calls for a root cause analysis to identify components of care that contributed to cases of neonatal encephalopathy to design better practices, surveillance mechanisms, and systems. All cases of infants born in New Zealand with moderate and severe neonatal encephalopathy were reported to the New Zealand Perinatal and Maternal Mortality Review Committee from 2010. A national clinical review of these individual cases has not previously been undertaken. The objective of the study was to undertake a multidisciplinary structured review of all cases of neonatal encephalopathy that arose following the onset of labor in the absence of acute peripartum events in 2010-2011 to determine the frequency of contributory factors, the proportion of potentially avoidable morbidity and mortality and to identify themes for quality improvement. National identification of, and collection of clinical records on, cases of moderate or severe neonatal encephalopathy occurring after the onset of labor in the absence of an acute peripartum event, excluding those with normal gases and Apgar scores at 1 minute, among all cases of moderate and severe neonatal encephalopathy at term in New Zealand in 2010-2011 was undertaken. Cases were included if they had abnormal gases as defined by any of pH of ≤ 7.2, base excess of ≤ -10, or lactate of ≥ 6 or if there were no cord gases, an Apgar score at 1 minute of ≤ 7. A clinical case review was undertaken by a multidisciplinary team using a structured tool to record contributory factors (organization and/or management, personnel, and barriers to access and/or engagement with care), potentially avoidable morbidity and mortality and to identify themes to guide quality improvement. Eighty-three babies fulfilled the inclusion criteria for the review, 56 moderate (67%) and 27 severe (33%), 21 (25%) of whom were

A case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Hazama, Kyoko; Shiihara, Takashi; Tsukagoshi, Hiroyuki; Hasegawa, Shunji; Dowa, Yuri; Watanabe, Mio

2017-10-01

Mumps is a common childhood viral disease characterized by fever and swelling of the parotid gland. The prognosis is generally good, although some complications, such as encephalitis (0.1%), exist. Acute encephalopathy with biphasic seizures and late reduced diffusion is the most common type of acute encephalopathy. However, this type of encephalopathy has not been reported in association with mumps infection. A previously healthy 3-year-old Japanese boy had a brief convulsion after fever for 3days, and then had conscious disturbance and parotitis. After several days, he had a second brief convulsion and was admitted. Increased serum amylase levels and presence of anti-mumps immunoglobulin M antibody confirmed mumps parotitis. The patient had another brief seizure later the day of admission. He did not have status or cluster seizures, although the biphasic nature of his seizures, conscious disturbance between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic resonance images were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion. In Japan, the mumps vaccine is not administered as a part of routine immunizations. It thus has low coverage (30-40%), and as a result, mumps infections are still common. However, this is the first case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion. This case may be representative of only a minority of patients with mumps-associated central nervous system involvement. Nevertheless, this diagnostic possibility may be considered. In order to prevent mumps-related complications, routine mumps vaccination might be warranted. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Liver transplant in ethylmalonic encephalopathy: a new treatment for an otherwise fatal disease.

PubMed

Dionisi-Vici, Carlo; Diodato, Daria; Torre, Giuliano; Picca, Stefano; Pariante, Rosanna; Giuseppe Picardo, Sergio; Di Meo, Ivano; Rizzo, Cristiano; Tiranti, Valeria; Zeviani, Massimo; De Ville De Goyet, Jean

2016-04-01

Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Posterior reversible encephalopathy syndrome induced by a cough and cold drug containing pseudoephedrine].

PubMed

Ebbo, M; Benarous, L; Thomas, G; Jourde, N; Genot, S; Bernit, E; Veit, V; Harlé, J-R; Schleinitz, N

2010-06-01

Posterior reversible encephalopathy syndrome is a clinico-radiological entity characterized by neurologic symptoms in association with usually reversible bilateral posterior hemispheric oedema on neuroimaging. Many pathological conditions and treatments have been associated with this syndrome. We report a 19-year-old woman, followed-up for hypocomplementemic urticarial vasculitis, who presented with a posterior reversible encephalopathy syndrome induced by the intake of an over-the-counter cold remedy containing pseudoephedrine. Clinical manifestations and radiological abnormalities resolved after anti-hypertensive therapy and withdrawal of sympathomimetic drug. The diagnosis of posterior reversible encephalopathy syndrome should be considered in patients with compatible clinical and radiological presentation because of its potential reversibility with an appropriate management. Intake of drugs, including over-the-counter cough and cold drugs, should be looked for in the history as well as autoimmune disorders. Copyright 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity.

PubMed

Devaux, Jérôme; Abidi, Affef; Roubertie, Agathe; Molinari, Florence; Becq, Hélène; Lacoste, Caroline; Villard, Laurent; Milh, Mathieu; Aniksztejn, Laurent

2016-05-01

Mutations in the KCNQ2 gene encoding the voltage-gated potassium channel subunit Kv7.2 cause early onset epileptic encephalopathy (EOEE). Most mutations have been shown to induce a loss of function or to affect the subcellular distribution of Kv7 channels in neurons. Herein, we investigated functional consequences and subcellular distribution of the p.V175L mutation of Kv7.2 (Kv7.2(V175L) ) found in a patient presenting EOEE. We observed that the mutation produced a 25-40 mV hyperpolarizing shift of the conductance-voltage relationship of both the homomeric Kv7.2(V175L) and heteromeric Kv7.2(V175L) /Kv7.3 channels compared to wild-type channels and a 10 mV hyperpolarizing shift of Kv7.2(V175L) /Kv7.2/Kv7.3 channels in a 1:1:2 ratio mimicking the patient situation. Mutant channels also displayed faster activation kinetics and an increased current density that was prevented by 1 μm linopirdine. The p.V175L mutation did not affect the protein expression of Kv7 channels and its localization at the axon initial segment. We conclude that p.V175L is a gain of function mutation. This confirms previous observations showing that mutations having opposite consequences on M channels can produce EOEE. These findings alert us that drugs aiming to increase Kv7 channel activity might have adverse effects in EOEE in the case of gain-of-function variants. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Rabies: Rare Human Infection - Common Questions.

PubMed

Willoughby, Rodney E

2015-12-01

Rabies is an acute, rapidly progressive encephalitis that is almost always fatal. Prophylaxis is highly effective but economics limits disease control. The mechanism of death from rabies is unclear. It is poorly cytopathic and poorly inflammatory. Rabies behaves like an acquired metabolic disorder. There may be a continuum of disease severity. History of animal bite is rare. The diagnosis is often missed. Intermittent encephalopathy, dysphagia, hydrophobia and aerophobia, and focal paresthesias or myoclonic jerks suggest rabies. Laboratory diagnosis is cumbersome but sensitive. Treatment is controversial but survivors are increasingly reported, with good outcomes in 4 of 8 survivors. Copyright © 2015 Elsevier Inc. All rights reserved.

Heat stress presenting with encephalopathy and MRI findings of diffuse cerebral injury and hemorrhage.

PubMed

Guerrero, Waldo R; Varghese, Shaun; Savitz, Sean; Wu, Tzu Ching

2013-06-17

Heat stress results in multiorgan failure and CNS injury. There a few case reports in the literature on the neurological consequences of heat stress. We describe a patient with heat stress presenting with encephalopathy and bilateral cerebral, cerebellar, and thalamic lesions and intraventricular hemorrhage on MRI. Heat stress should be in the differential diagnosis of patients presenting with encephalopathy and elevated serum inflammatory markers especially if the history suggests a preceding episode of hyperthermia.

The risk of bovine spongiform encephalopathy ('mad cow disease') to human health.

PubMed

Brown, P

1997-09-24

Some human cases of the transmissible neurodegenerative disorder Creutzfeldt-Jakob disease recently seen in Great Britain are thought to have resulted from eating beef infected with the agent of bovine spongiform encephalopathy. Reasons for and against this presumption are explained, and the question of a similar situation occurring in countries other than Britain-in particular, the United States-is discussed in terms of the existence of scrapie (in sheep) or unrecognized bovine spongiform encephalopathy (in cattle), the practice of recycling nonedible sheep and cattle tissue for animal nutrition, and precautionary measures already taken or under consideration by government agencies

MRI and clinical manifestations of delayed encephalopathy after carbon monoxide poisoning.

PubMed

Wang, Xiahong; Li, Zhenyu; Berglass, Jacqueline; He, Wenlong; Zhao, Jianmin; Zhang, Min; Gao, Chongyang; Zhang, Caixia; Zhang, Huimin; Yi, Xuewei

2016-11-01

To explore the relationship between the clinical manifestations and functional magnetic resonance images of delayed encephalopathy after carbon monoxide intoxication. Six patients received the MRI were diagnosed with delayed encephalopathy after carbon monoxide (CO) poisoning. Clinical manifestations were observed in each patient. MRI revealed multiple lesions. The majority of the lesions were located in the globus pallidus, sub cortical white matter, and basal ganglia. The cognitive injury, akinetic mutism, fecal and uroclepsia, forced crying, forced laughing and extra pyramidal syndromes such as chorea and parkinsonism were manifested in clinic. Cognitive impairment improved greatly while involuntary movements only improved slightly after several months. Meanwhile brain MRI suggested remarkable improvement. Neuroimaging directly correlated with the clinical manifestations.

Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

PubMed

Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

2014-07-01

Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

[Congenital intrahepatic venous shunt as a cause of hepatic encephalopathy].

PubMed

Cosme Jiménez, A; Bujanda Fernández de Piérola, L; Poch Zapiraín, M; Orcolaga Alba, R; Ojeda Pérez, E; Arenas Miravé, J I

1995-11-01

Macroscopic intrahepatic portosystemic shunts are extremely rare and may be due to liver injury, congenital vascular malformations or pathologic collaterals secondary to portal hypertension. Forty-eight cases have been reported in the literature up to 1994 with 50-60% presenting cerebral manifestations and 40% being associated with cirrhosis. The case of a patient without cirrhosis who was admitted for upper digestive hemorrhage secondary to gastroduodenal ulcer is described. At 48 hours the patient had an episode of hepatic encephalopathy coinciding with bleeding reactivation. Abdominal echography suggested communication between the right portal and suprahepatic veins and posterior angiography confirmed the diagnosis. Color Doppler echography determined shunt and portal vein blood flow. No case of intrahepatic portosystemic venous shunt as a cause of encephalopathy was found to have been reported in the Spanish literature.

Prognostic factors for acute encephalopathy with bright tree appearance.

PubMed

Azuma, Junji; Nabatame, Shin; Nakano, Sayaka; Iwatani, Yoshiko; Kitai, Yukihiro; Tominaga, Koji; Kagitani-Shimono, Kuriko; Okinaga, Takeshi; Yamamoto, Takehisa; Nagai, Toshisaburo; Ozono, Keiichi

2015-02-01

To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation. We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings. Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p=0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p<0.05) and minimal platelet counts were significantly lower (p<0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group. Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Late-onset childhood neuronal ceroid lipofuscinosis: Early clinical and electroencephalographic markers.

PubMed

Beltrán, Lucas; Valenzuela, Gabriela Reyes; Loos, Mariana; Vargas, Rodrigo; Lizama, Rafael; Spinsanti, Pablo; Caraballo, Roberto

2018-05-15

The objective of the study was to describe the initial clinical and electroencephalographic findings in children with late-infantile neuronal ceroid lipofuscinosis (LINCL). The clinical charts of 35 patients seen between 1990 and 2016 were reviewed. The patients were divided into two groups: Group 1 (G1) consisting of 12 patients with NCL type 2 (CLN2) disease confirmed by enzymatic activity in dried blood spots on filter paper and/or genetic studies, and Group 2 (G2) consisting of 23 patients with a diagnosis of LINCL based on pathology studies by muscle biopsy. Mean age at symptom onset was 3 years in G1 and 3.4 years in G2. Symptoms at onset were epilepsy in 58%, language delay in 34%, and gait disturbances in 8% of patients in G1 and epilepsy in 52.1%, language delay in 26%, gait disturbances in 17.4%, and loss of visual acuity in 4.5% in G2. The most common seizure types in G1 patients were myoclonic in 3/7, generalized tonic-clonic in 2/7, focal motor in 1/7, and febrile seizures in 1/7; in G2 patients they were myoclonic in 5/12, generalized tonic-clonic in 3/12, myoclonic-atonic in 2/12, and febrile seizures in 2/12. A photoparoxysmal response to intermittent photic stimulation (IPS) was found in the initial EEG in 9/12 patients in G1 (mean age 3.8 years) and in 10/13 patients in G2 (mean age 3.9 years). There were no significant differences between both groups. Seizures, especially myoclonic, are the most common symptom at onset followed by language delay and gait disturbances. Low-frequency IPS is a useful study that may help facilitate the diagnosis of the disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Probiotics in management of hepatic encephalopathy.

PubMed

Sharma, Barjesh Chander; Singh, Jatinderpal

2016-12-01

Gut microflora leads to production of ammonia and endotoxins which play important role in the pathogenesis of hepatic encephalopathy (HE). There is relationship between HE and absorption of nitrogenous substances from the intestines. Probiotics play a role in treatment of HE by causing alterations in gut flora by decreasing the counts of pathogen bacteria, intestinal mucosal acidification, decrease in production and absorption of ammonia, alterations in permeability of gut, decreased endotoxin levels and changes in production of short chain fatty acids. Role of gut microbiota using prebiotics, probiotics and synbiotics have been evaluated in the management of minimal hepatic encephalopathy (MHE), overt HE and prevention of HE. Many studies have shown efficacy of probiotics in reduction of blood ammonia levels, treatment of MHE and prevention of HE. However these trials have problems like inclusion of small number of patients, short treatment durations, variability in HE/MHE related outcomes utilized and high bias risk, errors of systematic and random types. Systematic reviews also have shown different results with one systematic review showing clinical benefits whereas another concluded that probiotics do not have any role in treatment of MHE or HE. Also practical questions on optimal dose, ideal combination of organisms, and duration of treatment and persistence of benefits on long term follow-up are still to be clarified. At present, there are no recommendations for use of probiotics in patients with HE.

Risk management of transmissible spongiform encephalopathies in Asia.

PubMed

Ozawa, Y

2003-04-01

A questionnaire-based survey was distributed to the Office International des Epizooties (OIE: World organisation for animal health) Member Countries in Asia to assess the use of risk management for transmissible spongiform encephalopathies. The author presents a summary of 16 responses received in July 2002. The survey revealed that import risk analysis on bovine spongiform encephalopathy (BSE) is not routinely carried out in ten countries, indicating an urgent need for further training courses. Although the number of ruminants imported from Europe is relatively small, significant quantities of feedstuffs of ruminant origin have been imported into Asia, which may mean that the BSE agent could have reached domestic cattle in most countries. The external challenge has been considerably reduced in recent years as most countries in Asia banned the importation of feedstuffs from countries with BSE, but a few weak spots which enable imports of risk materials still persist. Recycling of BSE through rendering plants is unlikely but cannot be totally excluded in some countries such as the People's Republic of China, India, Japan, Pakistan and Taipei China. Therefore, much more stringent management at slaughterhouses and rendering plants, as well as extensive surveillance programmes, are required in those countries. Bovine spongiform encephalopathy is not notifiable in six countries, indicating a total absence of risk management of BSE in those countries. Immediate actions by these governments to declare BSE a notifiable disease are considered necessary. Numbers of specimens tested for BSE are still very small in most countries in Asia, indicating a pressing need to upgrade surveillance programmes by introducing modern (economically affordable) diagnostic methods and by conducting practical training courses on epidemiological surveillance systems. With the exception of Japan, very little work has been performed on scrapie in Asia although the disease has been routinely

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

PubMed

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P < 0.05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P < 0.05). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P < 0.05). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content (r = 0.536, P < 0.01; r = 0.566, P = 0.01). The high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Hepatic encephalopathy: cause and possible management with botanicals.

PubMed

Tripathi, Suyash; Tripathi, Yamini B

2014-01-01

Hepatic encephalopathy is a brain functional disorder, characterized by neuropsychiatric abnormalities with liver failure. High blood ammonia, causing glutamate neurotoxicity is the basic cause, finally leading to low-grade cerebral edema. Its manifestation is more likely in patients of sepsis, oxidative stress, generalized inflammation, gut mal-functioning, amoebiaesis, viral hepatitis, nervous imbalance, etc. Thus, the therapeutic goals primarily include the maintenance of proper blood supply and prevention of hypoxic condition in liver, along with management of factors responsible for high blood ammonia, oxidative stress, inflammation, and high GI- serotonin. The drugs in clinical practice include lactulose, sodium benzoate, flumazenil and rifaximin, supplementation of zinc, branched chain amino acids (BCAA), l-ornithine-l aspartate, antioxidants and iNOS inhibitors. However, herbal formulations would be of great importance as it shows multi-targeted action because it possesses a natural cocktail of secondary metabolites. It can collectively act as an antioxidant, anti-inflammatory, prebiotic, hepatoprotective and neuron-protective agents. We have briefly outlined some of these plants and also recent patents useful in the management of hepatic encephalopathy.

Sleep disturbances in juvenile myoclonic epilepsy: a sleep questionnaire-based study.

PubMed

Krishnan, Pramod; Sinha, Sanjib; Taly, Arun B; Ramachandraiah, Chaitra T; Rao, Shivaji; Satishchandra, Parthasarathy

2012-03-01

Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age- and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F=22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure- or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification. Copyright © 2012 Elsevier Inc. All rights reserved.

Medium chain triglycerides and hepatic encephalopathy

PubMed Central

Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.

1974-01-01

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

Encephalopathy due to tubercular otitis media.

PubMed

Gurjar, Mohan; Aggarwal, Sushil K; Saigal, Saurabh; Singh, Ratender K

2012-04-01

Middle ear infection due to Mycobacterium tuberculosis has been reduced from 3-5% to 0.05-0.9% in the last century due to advent of effective anti-tuberculosis therapy. On the other side, this decrease in frequency of tuberculous otitis media along with indistinguishable signs and symptoms of frequently occurring non-tuberculous otitis media makes clinicians vulnerable to delayed or misdiagnosis of the disease. A case of tubercular otitis media with atypical clinical manifestations in the form of encephalopathy is presented.

Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

ERIC Educational Resources Information Center

Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

2011-01-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

The effect of hemoperfusion on patients with toxic encephalopathy induced by silkworm chrysalis ingestion.

PubMed

Hu, Haixia; Wang, Xu; Lv, Jiaqi; Sun, Jing; Xing, Jihong; Liu, Xiaoliang

2016-08-01

This study aims to determine therapeutic effect of hemoperfusion on patients with acute toxic encephalopathy induced by silkworm chrysalis ingestion. Three patients who developed toxic encephalopathy after chrysalis ingestion were analysed. Two patients lost their consciousness, while two patients had typical extrapyramidal tremor symptoms. Further neurological examination revealed various degrees of muscle strength impairment in these patients. All of them received treatments of omeprazole (40 mg/day), furosemide (one dose of 20 mg), vitamin C (2.0 g/day), calcium gluconate (2.0 g/day) and rehydration with glucose and sodium chloride (1500 ml/day). In addition, they received hemoperfusion treatment for 1.5 h. All patients recovered well after hemoperfusion. Two patients with loss of consciousness significantly recovered at 45 min and 65 min after hemoperfusion, respectively. All tremor symptoms were completely resolved in these patients at 30 min, 50 min, and 70 min following treatment, respectively. After the hemoperfusion treatment, encephalopathy symptoms of two patients had completely disappeared. All patients were followed up for one month and did not report any abnormalities. Our study indicates that hemoperfusion could be a useful and efficient treatment strategy for patients with acute encephalopathy after silkworm chrysalis ingestion. Larger clinical trials with longer follow-up are warranted to confirm the clinical benefit of hemoperfusion. © The Author(s) 2015.

Effects of raloxifene on portal hypertension and hepatic encephalopathy in cirrhotic rats.

PubMed

Chang, Ching-Chih; Lee, Wen-Shin; Chuang, Chiao-Lin; Hsin, I-Fang; Hsu, Shao-Jung; Chang, Ting; Huang, Hui-Chun; Lee, Fa-Yauh; Lee, Shou-Dong

2017-05-05

Raloxifene, a selective estrogen receptor modulator, has been used extensively for osteoporosis. In addition to the effect of osteoporosis treatment, emerging evidences show that raloxifene affects the vascular function in different tissues. Cirrhosis is characterized with portal hypertension and complicated with hepatic encephalopathy. Portal hypertension affects portal-systemic shunt which leads to hepatic encephalopathy that the vascular modulation might influence severity of hepatic encephalopathy. Herein, we evaluated the impact of raloxifene on bile duct ligation (BDL)-induced cirrhotic rats. The female Sprague-Dawley rats received BDL plus ovariectomy or sham-operation. Four weeks later, rats were divided into 2 subgroups respectively to receive of raloxifene (10mg/kg/day) or saline (vehicle) for 14 days. On the 43th day, motor activities and hemodynamic parameters were measured. Hepatic and vascular mRNA and protein expressions were determined. The histopathological change of liver was examined. We found that the liver biochemistry, ammonia level and motor activity were similar between cirrhotic rats with or without raloxifene administration. The hemodynamic parameters were not significantly different except that raloxifene reduced portal venous inflow. Raloxifene exacerbated hepatic fibrosis and up-regulated hepatic endothelin-1 and cyclooxygenase 2 protein expressions. In addition, raloxifene modulated the mRNA expressions of endothelial nitric oxide synthase, cyclooxygenase and endothelin-1 in the superior mesenteric artery and collateral vessel. In conclusion, raloxifene aggravates hepatic fibrosis and decreases portal venous inflow in cirrhotic rats without adversely affecting portal hypertension and hepatic encephalopathy. The modulation of hepatic and vascular endothelin-1, endothelial nitric oxide synthase and cyclooxygenase expressions may play a role in the mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

[Subacute encephalopathy with epileptic seizures in an alcoholic patient].

PubMed

Kozian, R; Otto, F G

2000-09-01

We introduce a case of a 66 year-old male with chronic alcoholism who suffered from confusion, Wernicke-aphasia and epileptic seizures. Several EEG revealed periodic lateralized epileptiform discharges. The patient's case resembles the symptoms of a subacute encephalopathy with epileptic seizures which can occur in alcoholics.

Presumptive Iatrogenic Microcystin-Associated Liver Failure and Encephalopathy in a Holsteiner Gelding.

PubMed

Mittelman, N S; Engiles, J B; Murphy, L; Vudathala, D; Johnson, A L

2016-09-01

An 8-year-old Holsteiner gelding was presented for evaluation of anorexia, obtundation, icterus, and mild colic signs of 48 hours duration. History, physical examination, and initial diagnostics were suggestive of hepatic disease and encephalopathy. Microcystin toxicosis was suspected based on historical administration of a cyanobacteria supplement, associated serum biochemistry abnormalities, and characteristic histopathological changes. Microcystin contamination was confirmed in both supplement containers fed to the horse. Fulminant hepatic failure and encephalopathy progressed resulting in euthanasia. Necropsy findings were consistent with microcystin induced liver failure. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Activated microglia in acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Fujita, Yuji; Takanashi, Jun-Ichi; Takei, Haruka; Ota, Setsuo; Fujii, Katsunori; Sakuma, Hiroshi; Hayashi, Masaharu

2016-07-15

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. The exact pathogenesis of and the best therapeutic strategy for AESD are uncertain. We firstly performed a brain biopsy in a 2-year-old boy with AESD associated with RS viral infection, which revealed activated ameoboid microglia accumulation around degenerated neuron, and astrogliosis in the affected cortex. Glutamate released from activated microglia may play an important role in the pathogenesis of AESD, which is compatible with the previous report of magnetic resonance spectroscopy showing elevated glutamate. Copyright © 2016 Elsevier B.V. All rights reserved.

[Bio-ecological control of chronic liver disease and encephalopathy].

PubMed

Bengmark, S; Di Cocco, P; Clemente, K; Corona, L; Angelico, R; Manzia, T; Famulari, A; Pisani, F; Orlando, G

2011-08-01

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy

USDA-ARS?s Scientific Manuscript database

Transmissible mink encephalopathy (TME) is a prion disorder of farmed raised mink. As with the other transmissible spongiform encephalopathies, the disorder is associated with accumulation of the misfolded prion protein in the brain and an invariably fatal outcome. TME outbreaks have been rare but...

Prospective research on infants with mild encephalopathy: the PRIME study.

PubMed

Prempunpong, C; Chalak, L F; Garfinkle, J; Shah, B; Kalra, V; Rollins, N; Boyle, R; Nguyen, K-A; Mir, I; Pappas, A; Montaldo, P; Thayyil, S; Sánchez, P J; Shankaran, S; Laptook, A R; Sant'Anna, G

2018-01-01

To determine short-term outcomes of infants with evidence of hypoxia-ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age. Prospective multicenter study. Mild NE was defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge. A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing. A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.

Encephalopathy after bladder irrigation with alum: case report and literature review.

PubMed

Phelps, K R; Naylor, K; Brien, T P; Wilbur, H; Haqqie, S S

1999-09-01

A 70-year-old man with advanced obstructive nephropathy began to hemorrhage from the bladder after decompression with a Foley catheter. Manifestations of encephalopathy appeared after continuous irrigation with 1% alum for 2 days and were associated with elevated serum aluminum concentrations. Repeated treatments with deferoxamine and hemodialysis accomplished some aluminum removal, but the patient succumbed to bronchopneumonia. Brain aluminum content was not excessive at autopsy. A literature review suggests that intact renal function is essential to rapid disposal of a parenteral aluminum load and indicates that most reported instances of encephalopathy after alum irrigation have occurred in patients with compromised renal function. We conclude that alum should not be employed as a bladder irrigant in patients with acute or chronic renal failure.

Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns.

PubMed

Chaparro-Huerta, Verónica; Flores-Soto, Mario Eduardo; Merin Sigala, Mario Ernesto; Barrera de León, Juan Carlos; Lemus-Varela, María de Lourdes; Torres-Mendoza, Blanca Miriam de Guadalupe; Beas-Zárate, Carlos

2017-02-01

Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models. Copyright © 2016. Published by Elsevier B.V.

Cerebral palsy after neonatal encephalopathy: do neonates with suspected asphyxia have worse outcomes?

PubMed

Garfinkle, Jarred; Wintermark, Pia; Shevell, Michael I; Oskoui, Maryam

2016-02-01

We sought to investigate how brain injury and severity, and neurological subtype of cerebral palsy (CP) differed in term-born children with CP after neonatal encephalopathy, between those with suspected birth asphyxia and those without. Using the Canadian CP Registry, which included 1001 children, those with CP born at ≥ 36 wks after moderate or severe neonatal encephalopathy, were dichotomized according to the presence or absence of suspected birth asphyxia. Gross Motor Function Classification System (GMFCS) scores, neurological subtypes, comorbidities, and magnetic resonance imaging findings were compared. Of the 147 term-born children with CP (82 males, 65 females; median age 37 months, interquartile range [IQR] 26-52.5) who after moderate or severe neonatal encephalopathy had the required outcome data, 61 (41%) met criteria for suspected birth asphyxia. They had a higher frequency of non-ambulatory GMFCS status (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.72-6.8), spastic quadriplegia (OR 2.8, 95% CI 1.4-5.6), non-verbal communication skills impairment (OR 4.2, 95% CI 2.0-8.6), isolated deep grey matter injury (OR 4.1, 95% CI 1.8-9.5), a lower frequency of spastic hemiplegia (OR 0.17, 95% CI 0.07-0.42), focal injury (OR 0.20; 95% CI 0.04-0.93), and more comorbidities (p=0.017) than those who did not meet criteria. Term-born children who develop CP after neonatal encephalopathy with suspected birth asphyxia have a greater burden of disability than those without suspected birth asphyxia. © 2015 Mac Keith Press.

Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy

PubMed Central

Avallone, R; Zeneroli, M; Venturini, I; Corsi, L; Schreier, P; Kleinschnitz, M; Ferrarese, C; Farina, F; Baraldi, C; Pecora, N; Frigo, M; Baraldi, M

1998-01-01

Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines. 
Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. 
Methods—Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. 
Results—Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased. 
Conclusions—Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy. 

 Keywords: benzodiazepine consumers; diazepam binding inhibitor; endogenous benzodiazepines; liver cirrhosis; overt hepatic encephalopathy PMID:9691927

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline

PubMed Central

2014-01-01

Background Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Methods Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Results Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. Conclusions These findings suggest that CCL2 is elevated systemically following acute liver injury

Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline.

PubMed

McMillin, Matthew; Frampton, Gabriel; Thompson, Michelle; Galindo, Cheryl; Standeford, Holly; Whittington, Eric; Alpini, Gianfranco; DeMorrow, Sharon

2014-07-10

Acute liver failure leads to systemic complications with one of the most dangerous being a decline in neurological function, termed hepatic encephalopathy. Neurological dysfunction is exacerbated by an increase of toxic metabolites in the brain that lead to neuroinflammation. Following various liver diseases, hepatic and circulating chemokines, such as chemokine ligand 2 (CCL2), are elevated, though their effects on the brain following acute liver injury and subsequent hepatic encephalopathy are unknown. CCL2 is known to activate microglia in other neuropathies, leading to a proinflammatory response. However, the effects of CCL2 on microglia activation and the pathogenesis of hepatic encephalopathy following acute liver injury remain to be determined. Hepatic encephalopathy was induced in mice via injection of azoxymethane (AOM) in the presence or absence of INCB 3284 dimesylate (INCB), a chemokine receptor 2 inhibitor, or C 021 dihydrochloride (C021), a chemokine receptor 4 inhibitor. Mice were monitored for neurological decline and time to coma (loss of all reflexes) was recorded. Tissue was collected at coma and used for real-time PCR, immunoblots, ELISA, or immunostaining analyses to assess the activation of microglia and consequences on pro-inflammatory cytokine expression. Following AOM administration, microglia activation was significantly increased in AOM-treated mice compared to controls. Concentrations of CCL2 in the liver, serum, and cortex were significantly elevated in AOM-treated mice compared to controls. Systemic administration of INCB or C021 reduced liver damage as assessed by serum liver enzyme biochemistry. Administration of INCB or C021 significantly improved the neurological outcomes of AOM-treated mice, reduced microglia activation, reduced phosphorylation of ERK1/2, and alleviated AOM-induced cytokine upregulation. These findings suggest that CCL2 is elevated systemically following acute liver injury and that CCL2 is involved in both the

Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

PubMed

Hughes, Adrienne; Brown, Alisha; Valento, Matthew

2016-09-01

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.

Molecular and genetic insights into an infantile epileptic encephalopathy - CDKL5 disorder.

PubMed

Zhou, Ailing; Han, Song; Zhou, Zhaolan Joe

2017-02-01

The discovery that mutations in cyclin-dependent kinase-like 5 ( CDKL5 ) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes.

Predictive value of EEG in postanoxic encephalopathy: A quantitative model-based approach.

PubMed

Efthymiou, Evdokia; Renzel, Roland; Baumann, Christian R; Poryazova, Rositsa; Imbach, Lukas L

2017-10-01

The majority of comatose patients after cardiac arrest do not regain consciousness due to severe postanoxic encephalopathy. Early and accurate outcome prediction is therefore essential in determining further therapeutic interventions. The electroencephalogram is a standardized and commonly available tool used to estimate prognosis in postanoxic patients. The identification of pathological EEG patterns with poor prognosis relies however primarily on visual EEG scoring by experts. We introduced a model-based approach of EEG analysis (state space model) that allows for an objective and quantitative description of spectral EEG variability. We retrospectively analyzed standard EEG recordings in 83 comatose patients after cardiac arrest between 2005 and 2013 in the intensive care unit of the University Hospital Zürich. Neurological outcome was assessed one month after cardiac arrest using the Cerebral Performance Category. For a dynamic and quantitative EEG analysis, we implemented a model-based approach (state space analysis) to quantify EEG background variability independent from visual scoring of EEG epochs. Spectral variability was compared between groups and correlated with clinical outcome parameters and visual EEG patterns. Quantitative assessment of spectral EEG variability (state space velocity) revealed significant differences between patients with poor and good outcome after cardiac arrest: Lower mean velocity in temporal electrodes (T4 and T5) was significantly associated with poor prognostic outcome (p<0.005) and correlated with independently identified visual EEG patterns such as generalized periodic discharges (p<0.02). Receiver operating characteristic (ROC) analysis confirmed the predictive value of lower state space velocity for poor clinical outcome after cardiac arrest (AUC 80.8, 70% sensitivity, 15% false positive rate). Model-based quantitative EEG analysis (state space analysis) provides a novel, complementary marker for prognosis in postanoxic

Serial cytokine alterations and abnormal neuroimaging in newborn infants with encephalopathy.

PubMed

O'Hare, Fiona M; Watson, R William G; O'Neill, Amanda; Segurado, Ricardo; Sweetman, Deirdre; Downey, Paul; Mooney, Eoghan; Murphy, John; Donoghue, Veronica; Molloy, Eleanor J

2017-04-01

Inflammatory cytokines may play a role in the final common pathway in the pathogenesis of hypoxic-ischaemic injury in experimental models. We aimed to profile the systemic pro-and anti-inflammatory response over the first week of life in term infants at risk of neonatal encephalopathy. In a tertiary referral university neonatal intensive care unit, serial blood samples were analysed from 41 term infants (requiring resuscitation at birth) in this prospective observational pilot study. Serum levels of 10 pro-and anti-inflammatory cytokines were evaluated including interleukin(IL)-1α, IL-1β, IL-6, IL-8, IL-10, tumour necrosis factor(TNF)-α, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), granulocyte/colony-stimulating factor (G-CSF) and granulocyte macrophage/colony-stimulating factor (GM-CSF). Infants with neonatal encephalopathy and abnormal neuroimaging (n = 15) had significantly elevated granulocyte macrophage/colony-stimulating factor at 0-24 h and interleukin-8, interleukin-6 and interleukin-10 at 24-48 hour. Tumour necrosis factor-α and vascular endothelial growth factor levels were lower at 72-96 hour (p < 0.05). Significantly elevated levels of interleukin-10 were associated with mortality. Serum cytokine changes and innate immune dysregulation in the first week of life may be indicators of outcome in neonatal encephalopathy but require validation in larger studies. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

PubMed

Sartori, Stefano; Di Rosa, Gabriella; Polli, Roberta; Bettella, Elisa; Tricomi, Giovanni; Tortorella, Gaetano; Murgia, Alessandra

2009-02-01

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures. (c) 2009 Wiley-Liss, Inc.

[Star fruit (Averrhoa carambola) toxic encephalopathy].

PubMed

Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D

2009-03-01

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.

Is there a creative functional paradoxical facilitation in juvenile myoclonic epilepsy?

PubMed

Senf, Philine; Scheuren, Lena; Holtkamp, Martin

2016-09-01

In patients with juvenile myoclonic epilepsy (JME), a specific personality profile suggestive of frontal lobe dysfunctions has been described. From a neurobiological point of view, the frontal lobe seems to be crucial for creative processes, although the exact role remains unclear. The theory of creative paradoxical functional facilitation (PFF) assumes that disinhibited frontal lobe function can enhance creative abilities. The aim of the current study was to explore our hypothesis that JME is associated with higher artistic creativity based on the theory of PFF. We assessed 25 patients with JME aged 18 to 40years in regard to neuropsychological creativity testing. Results were compared with those of 25 age-, sex-, and level of education-matched healthy control subjects (HC) and patients with temporal lobe epilepsy (TLE). Creative abilities were assessed using two validated and standardized tests: 1) nonverbal: the incomplete figure task of Torrance Test of Creative Thinking and 2) verbal: verbal creativity test. Additionally, a basic assessment of fluid intelligence (test for problem solving) and frontal lobe function (trail-making test) was administered to all participants. Verbal creativity was impaired in both groups with epilepsy compared with that in HC (specific score: JME vs. HC, p=0.008; TLE vs. HC, p=0.003). In regard to nonverbal creative abilities, both groups with epilepsy exhibited fair performance. Level of fluid intelligence was even in all groups (p=0.433). Only patients with JME showed deficits in the frontal lobe test of psychomotor speed (time in seconds: 67.7 JME vs. 54.6 TLE vs. 52.8 HC; p=0.045). Overall, our study did not reveal increased creativity in JME. The current findings provide insights into creative abilities in two different epilepsy syndromes. Knowledge on specific neuropsychological strengths or deficits in patients with epilepsy may be useful for treatment or counseling. Copyright © 2016 Elsevier Inc. All rights reserved.

A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia.

PubMed

Akamine, Satoshi; Ishizaki, Yoshito; Sakai, Yasunari; Torisu, Hiroyuki; Fukai, Ryoko; Miyake, Noriko; Ohkubo, Kazuhiro; Koga, Hiroshi; Sanefuji, Masafumi; Sakata, Ayumi; Kimura, Masahiko; Yamaguchi, Seiji; Sakamoto, Osamu; Hara, Toshiro; Saitsu, Hirotomo; Matsumoto, Naomichi; Ohga, Shouichi

2018-03-03

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy. Copyright © 2018. Published by Elsevier Masson SAS.

High-fat diets and seizure control in myoclonic-astatic epilepsy: a single center's experience.

PubMed

Simard-Tremblay, Elisabeth; Berry, Patricia; Owens, Aaron; Cook, William Byron; Sittner, Haley R; Mazzanti, Marta; Huber, Jennifer; Warner, Molly; Shurtleff, Hillary; Saneto, Russell P

2015-02-01

To determine the efficacy of the Modified Atkins Diet (MAD) and Ketogenic Diet (KD) in seizure control within a population of myoclonic-astatic epilepsy (MAE) patients. This was a retrospective, single center study evaluating the seizure control by high fat diets. Seizure diaries kept by the parents performed seizure counts. All patients met the clinical criteria for MAE. Nine patients met the clinical criteria. We found that both the MAD and KD were efficacious in complete seizure control and allowed other medications to be stopped in seven patients. Two patients had greater than 90% seizure control without medications, one on the KD and the other on the MAD. Seizure freedom has ranged from 13 to 36 months, and during this time four patients have been fully weaned off of diet management. One patient was found to have a mutation in SLC2A1. Our results suggest that strictly defined MAE patients respond to the MAD with prolonged seizure control. Some patients may require the KD for seizure freedom, suggesting a common pathway of increased requirement for fats. Once controlled, those fully responsive to the Diet(s) could be weaned off traditional seizure medications and in many, subsequently off the MAD or KD. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

[Immune system aging rate in patients with early forms of chronic cerebrovascular diseases].

PubMed

Kochetkova, N G; Al'tman, D Sh; Teplova, S N

2009-01-01

Using the Bioage and Snake software the immune and cardiovascular system aging rate was diagnosed in patients having early forms of chronic cerebrovascular diseases (CCVD). The indicators of biological, cardiopulmonary and immunological age were studied in patients showing early symptoms of cerebrovascular insufficiency and dyscirculatory encephalopathy of the 1st stage. The rate of age-dependent physiological changes was diagnosed compared to general body aging rate. Some specific patterns of immune system aging were found in patients with early forms of CCVDs, the cardinal aging symptoms (heterotropia, heterochronia) were verified.

Familial acute necrotizing encephalopathy without RANBP2 mutation: Poor outcome.

PubMed

Nishimura, Naoko; Higuchi, Yoshihisa; Kimura, Nobusuke; Nozaki, Fumihito; Kumada, Tomohiro; Hoshino, Ai; Saitoh, Makiko; Mizuguchi, Masashi

2016-11-01

Most childhood cases of acute necrotizing encephalopathy (ANE) involve neither family history nor recurrence. ANE occasionally occurs, however, as a familial disorder or recurs in Caucasian patients. A mutation of RAN-binding protein 2 (RANBP2) has been discovered in more than one half of familial or recurrent ANE patients. In contrast, there has been no report of this mutation in East Asia. Here, we report the first sibling cases of typical ANE in Japan, with poor outcome. DNA analysis of genes associated with ANE or other encephalopathies, including RANBP2 and carnitine palmitoyl transferase II (CPT2), indicated neither mutations nor disease-related polymorphisms. On literature review, recurrent or familial ANE without the RANBP2 mutation has a more severe outcome and greater predilection for male sex than that with the RANBP2 mutation. This suggests that there are unknown gene mutations linked to ANE. © 2016 Japan Pediatric Society.

Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

PubMed

Pillitteri, C A; Craig, L E

2013-01-01

Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage Gated Potassium Channel Mediated Seizures.

PubMed

Sirsi, Deepa; Dolce, Alison; Greenberg, Benjamin M; Thodeson, Drew

2016-01-01

There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis. We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization. This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes.

Management of hepatic encephalopathy in the hospital.

PubMed

Leise, Michael D; Poterucha, John J; Kamath, Patrick S; Kim, W Ray

2014-02-01

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

Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

PubMed Central

Hughes, Adrienne; Brown, Alisha; Valento, Matthew

2016-01-01

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

Hyperammonemic encephalopathy due to suture line breakdown after bladder operation.

PubMed

Boogerd, W; Zoetmulder, F A; Moffie, D

1990-01-01

A patient is described with a severe encephalopathy and hyperammonemia in absence of liver dysfunction, attributed to urine absorption into the systemic circulation due to suture line breakdown after bladder dome resection. At autopsy characteristic Alzheimer type II astrocytes were found in the basal ganglia.

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison.

PubMed

Bianchi, G P; Marchesini, G; Fabbri, A; Rondelli, A; Bugianesi, E; Zoli, M; Pisi, E

1993-05-01

In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.

Orthotopic liver transplantation for portosystemic encephalopathy in an adult with congenital absence of the portal vein.

PubMed

Wojcicki, Maciej; Haagsma, Elizabeth B; Gouw, Annette S H; Slooff, Maarten J H; Porte, Robert J

2004-09-01

Congenital absence of the portal vein (CAPV) is a very rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. There is no portal perfusion of the liver and no portal hypertension. This abnormality is usually coincidentally discovered in children, the majority of whom have no signs of encephalopathy and only slightly abnormal liver function tests. Additional anomalies common in CAPV are cardiovascular abnormalities and hepatic tumors. To date, only 5 adult patients (>18 years) with CAPV have been described, none of whom underwent liver transplantation. We describe a 45-year-old man with CAPV and end-stage renal insufficiency due to focal segmental glomerulopathy, who developed therapy-resistant encephalopathy with intermittently high ammonia levels. The patient underwent a combined liver and kidney transplantation and is doing well at 2.5 years of follow-up. Histopathological examination of the native liver showed no portal vein branches in the portal tracts. In conclusion, our experience suggests that, although children with CAPV usually have no symptoms of encephalopathy, this may still develop at a later stage in adult life. When encephalopathy becomes refractory to medical therapy, orthotopic liver transplantation (OLT) can be successfully performed with restoration of normal cerebral function.

Transition from upbeat to downbeat nystagmus observed in a patient with Wernicke's encephalopathy.

PubMed

Suzuki, Yasuo; Matsuda, Taisuke; Washio, Noriaki; Ohtsuka, Kenji

2005-01-01

We report an unusual case of Wernicke's encephalopathy presenting with transient upbeat nystagmus that changed to a persistent downbeat nystagmus. A 27-year-old man presented with upbeat nystagmus. Three months earlier, he had been diagnosed with Wernicke's encephalopathy after fasting for a month. This diagnosis was supported by his symptoms (ataxia, a confused state). Clinical recovery followed thiamine therapy. His upbeat nystagmus had linear slow phases with average amplitude and frequency (+/-SD) during fixation straight ahead of 2.8 +/- 0.7 degrees and 4.6 +/- 2.2 Hz, respectively. Two months later, the primary position upbeat nystagmus had diminished and downbeat nystagmus (0.9 +/- 0.5 degrees and 3.2 +/- 0.7 Hz on average) for a 20 degrees downward gaze had developed. Then, 8 months later, he showed only downbeat nystagmus, which obeyed Alexander's law. His primary position downbeat nystagmus was completely suppressed by clonazepam, a gamma-aminobutyric acid (GABA) agonist. Owing to an underlying central vestibular imbalance, even after the recovery of acute neurological symptoms, Wernicke's encephalopathy can be complicated by persistent downbeat nystagmus, which can be treated by a GABA agonist.

Autoimmune encephalopathies

PubMed Central

Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

2014-01-01

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

Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

PubMed

Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

2015-07-01

Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Ammonia and amino acid profiles in liver cirrhosis: effects of variables leading to hepatic encephalopathy.

PubMed

Holecek, Milan

2015-01-01

Hyperammonemia and severe amino acid imbalances play central role in hepatic encephalopathy (HE). In the article is demonstrated that the main source of ammonia in cirrhotic subjects is activated breakdown of glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is ammonia detoxification to GLN in the brain and skeletal muscle. Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) decrease due to activated GLN synthesis in muscle. Aromatic amino acids (AAA; phenylalanine, tyrosine, and tryptophan) and methionine increase due to portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of liver disease are discussed: nutritional status, starvation, protein intake, inflammation, acute hepatocellular damage, bleeding from varices, portosystemic shunts, hepatic cancer, and renal failure. It is concluded that (1) neither ammonia nor amino acid concentrations correlate closely with the severity of liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in amino acid metabolism; (3) variables potentially leading to overt encephalopathy exert substantial but uneven effects; and (4) careful monitoring of ammonia and aminoacidemia may discover important break points in the course of liver disease and indicate appropriate therapeutic approach. Of special importance might be isoleucine deficiency in bleeding from varices, arginine deficiency in sepsis, and a marked rise of GLN and ammonia levels that may appear in all events leading to HE. Copyright © 2015 Elsevier Inc. All rights reserved.

Rapid Typing of Transmissible Spongiform Encephalopathy Strains with Differential ELISA

PubMed Central

Simon, Stéphanie; Nugier, Jérôme; Morel, Nathalie; Boutal, Hervé; Créminon, Christophe; Benestad, Sylvie L.; Andréoletti, Olivier; Lantier, Frédéric; Bilheude, Jean-Marc; Feyssaguet, Muriel; Biacabe, Anne-Gaëlle; Baron, Thierry

2008-01-01

The bovine spongiform encephalopathy (BSE) agent has been transmitted to humans, leading to variant Creutzfeldt-Jakob disease. Sheep and goats can be experimentally infected by BSE and have been potentially exposed to natural BSE; however, whether BSE can be transmitted to small ruminants is not known. Based on the particular biochemical properties of the abnormal prion protein (PrPsc) associated with BSE, and particularly the increased degradation induced by proteinase K in the N terminal part of PrPsc, we have developed a rapid ELISA designed to distinguish BSE from other scrapie strains. This assay clearly discriminates experimental ovine BSE from other scrapie strains and was used to screen 260 transmissible spongiform encephalopathy (TSE)–infected small ruminant samples identified by the French active surveillance network (2002/2003). In this context, this test has helped to identify the first case of natural BSE in a goat and can be used to classify TSE isolates based on the proteinase K sensitivity of PrPsc. PMID:18394279

Brainstem removal using compressed air for subsequent bovine spongiform encephalopathy testing

PubMed Central

2005-01-01

Abstract The use of compressed air to expel the obex through a hole in the skull generated using a captured bolt stunner. The obex is the part of the brain that is tested for bovine spongiform encephalopathy. PMID:16018564

A Case of Subacute Encephalopathy Developing After Treatment With Clofarabine and Methotrexate That Resolved With Corticosteroids.

PubMed

Tzachanis, Dimitrios; Haider, Mintallah; Papazisis, Georgios

2016-01-01

This is the case of a 24-year-old woman with relapsed acute undifferentiated leukemia who developed subacute encephalopathy with hemiparesis and dysarthria after treatment with high dose and intrathecal methotrexate, clofarabine, and cytarabine that resolved rapidly and completely after the administration of corticosteroids. We hypothesize that clofarabine might predispose to methotrexate-induced central nervous system toxicity by increasing endothelial permeability (capillary leak syndrome) and suggest that corticosteroids are effective in the treatment of this type of encephalopathy.

Molecular and genetic insights into an infantile epileptic encephalopathy – CDKL5 disorder

PubMed Central

Zhou, Ailing; Han, Song

2017-01-01

Background The discovery that mutations in cyclin-dependent kinase-like 5 (CDKL5) gene are associated with infantile epileptic encephalopathy has stimulated world-wide research effort to understand the molecular and genetic basis of CDKL5 disorder. Given the large number of literature published thus far, this review aims to summarize current genetic studies, draw a consensus on proposed molecular functions, and point to gaps of knowledge in CDKL5 research. Methods A systematic review process was conducted using the PubMed search engine focusing on CDKL5 studies in the recent ten years. We analyzed these publications and summarized the findings into four sections: genetic studies, CDKL5 expression patterns, molecular functions, and animal models. We also discussed challenges and future directions in each section. Results On the clinical side, CDKL5 disorder is characterized by early onset epileptic seizures, intellectual disability, and stereotypical behaviors. On the research side, a series of molecular and genetic studies in human patients, cell cultures and animal models have established the causality of CDKL5 to the infantile epileptic encephalopathy, and pointed to a key role for CDKL5 in regulating neuronal function in the brain. Mouse models of CDKL5 disorder have also been developed, and notably, manifest behavioral phenotypes, mimicking numerous clinical symptoms of CDKL5 disorder and advancing CDKL5 research to the preclinical stage. Conclusions Given what we have learned thus far, future identification of robust, quantitative, and sensitive outcome measures would be the key in animal model studies, particularly in heterozygous females. In the meantime, molecular and cellular studies of CDKL5 should focus on mechanism-based investigation and aim to uncover druggable targets that offer the potential to rescue or ameliorate CDKL5 disorder-related phenotypes. PMID:28580010

Retinal function and morphology are altered in cattle infected with the prion disease transmissible mink encephalopathy.

PubMed

Smith, J D; Greenlee, J J; Hamir, A N; Richt, J A; Greenlee, M H West

2009-09-01

Transmissible spongiform encephalopathies (TSEs) are a group of diseases that result in progressive and invariably fatal neurologic disease in both animals and humans. TSEs are characterized by the accumulation of an abnormal protease-resistant form of the prion protein in the central nervous system. Transmission of infectious TSEs is believed to occur via ingestion of prion protein-contaminated material. This material is also involved in the transmission of bovine spongiform encephalopathy ("mad cow disease") to humans, which resulted in the variant form of Creutzfeldt-Jakob disease. Abnormal prion protein has been reported in the retina of TSE-affected cattle, but despite these observations, the specific effect of abnormal prion protein on retinal morphology and function has not been assessed. The objective of this study was to identify and characterize potential functional and morphologic abnormalities in the retinas of cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy. We used electroretinography and immunohistochemistry to examine retinas from 10 noninoculated and 5 transmissible mink encephalopathy-inoculated adult Holstein steers. Here we show altered retinal function, as evidenced by prolonged implicit time of the electroretinogram b-wave, in transmissible mink encephalopathy-infected cattle before the onset of clinical illness. We also demonstrate disruption of rod bipolar cell synaptic terminals, indicated by decreased immunoreactivity for the alpha isoform of protein kinase C and vesicular glutamate transporter 1, and activation of Müller glia, as evidenced by increased glial fibrillary acidic protein and glutamine synthetase expression, in the retinas of these cattle at the time of euthanasia due to clinical deterioration. This is the first study to identify both functional and morphologic alterations in the retinas of TSE-infected cattle. Our results support future efforts to focus on the retina for the development of

Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.

PubMed

Ray, Paula; Hayward, Jean; Michelson, David; Lewis, Edwin; Schwalbe, Joan; Black, Steve; Shinefield, Henry; Marcy, Michael; Huff, Ken; Ward, Joel; Mullooly, John; Chen, Robert; Davis, Robert

2006-09-01

Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders. A retrospective case-control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date. Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45-3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51-2.98, P = 0.647). In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

PubMed

Gramegna, L L; Pisano, A; Testa, C; Manners, D N; D'Angelo, R; Boschetti, E; Giancola, F; Pironi, L; Caporali, L; Capristo, M; Valentino, M L; Plazzi, G; Casali, C; Dotti, M T; Cenacchi, G; Hirano, M; Giordano, C; Parchi, P; Rinaldi, R; De Giorgio, R; Lodi, R; Carelli, V; Tonon, C

2018-01-18

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N -acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to

CAD mutations and uridine-responsive epileptic encephalopathy.

PubMed

Koch, Johannes; Mayr, Johannes A; Alhaddad, Bader; Rauscher, Christian; Bierau, Jörgen; Kovacs-Nagy, Reka; Coene, Karlien L M; Bader, Ingrid; Holzhacker, Monika; Prokisch, Holger; Venselaar, Hanka; Wevers, Ron A; Distelmaier, Felix; Polster, Tilman; Leiz, Steffen; Betzler, Cornelia; Strom, Tim M; Sperl, Wolfgang; Meitinger, Thomas; Wortmann, Saskia B; Haack, Tobias B

2017-02-01

Unexplained global developmental delay and epilepsy in childhood pose a major socioeconomic burden. Progress in defining the molecular bases does not often translate into effective treatment. Notable exceptions include certain inborn errors of metabolism amenable to dietary intervention. CAD encodes a multifunctional enzyme involved in de novo pyrimidine biosynthesis. Alternatively, pyrimidines can be recycled from uridine. Exome sequencing in three families identified biallelic CAD mutations in four children with global developmental delay, epileptic encephalopathy, and anaemia with anisopoikilocytosis. Two died aged 4 and 5 years after a neurodegenerative disease course. Supplementation of the two surviving children with oral uridine led to immediate cessation of seizures in both. A 4-year-old female, previously in a minimally conscious state, began to communicate and walk with assistance after 9 weeks of treatment. A 3-year-old female likewise showed developmental progress. Blood smears normalized and anaemia resolved. We establish CAD as a gene confidently implicated in this neurometabolic disorder, characterized by co-occurrence of global developmental delay, dyserythropoietic anaemia and seizures. While the natural disease course can be lethal in early childhood, our findings support the efficacy of uridine supplementation, rendering CAD deficiency a treatable neurometabolic disorder and therefore a potential condition for future (genetic) newborn screening. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of urinary S100B protein level and lactate/creatinine ratio for early diagnosis and prognostic prediction of neonatal hypoxic-ischemic encephalopathy.

PubMed

Liu, Li; Zheng, Chong-Xun; Peng, Shu-Feng; Zhou, Hong-Yan; Su, Zu-You; He, Li; Ai, Ting

2010-01-01

Early identification and prevention of hypoxic-ischemic encephalopathy (HIE) in newborns may reduce neonatal mortality and neurological dysfunction. To analyze the diagnostic and prognostic values of urinary S100B level and lactate/creatinine ratio in newborns with HIE. Seventy-eight full-term newborns with HIE and 25 normal newborns were enrolled. The Neonatal Behavioral Neurological Assessment (NBNA) and Developmental Screening Test were scored. The concentration of urinary S100B protein was determined using the S100B enzyme-linked immunosorbent assay and the levels of urinary lactate and creatinine were measured with the enzyme colorimetric method. Urinary S100B level on days 1-3 after birth and lactate/creatinine ratio on day 1 were significantly higher in newborns with HIE than those in the control group. Both indexes were positively correlated with the clinical grading of HIE. A cutoff value for the S100B level of 0.47 microg/l on day 3 after birth had a sensitivity of 90% and specificity of 92% for prediction of HIE. A lactate/creatinine ratio of more than 0.55 on day 1 showed the highest sensitivity (92%) and specificity (90%). A combination of both indexes improved the sensitivity and specificity to 99 and 97%, respectively. A negative correlation of both lactate/creatinine ratio on day 1 and S100B level on days 1-3 after birth with the NBNA score was identified on days 3, 7 and 14 after birth. The Developmental Screening Test score of 36 newborns with HIE within 6 months after birth showed that 65% of infants with moderate and high HIE had an abnormal developmental quotient. These data suggest that early measurement of both S100B level and lactate/creatinine ratio in the urine of newborns with HIE is a practical convenient and sensitive way to improve diagnosis on the third day of life and prognostic prediction of HIE. Copyright 2009 S. Karger AG, Basel.

Glycogen Phosphomonoester Distribution in Mouse Models of the Progressive Myoclonic Epilepsy, Lafora Disease*

PubMed Central

DePaoli-Roach, Anna A.; Contreras, Christopher J.; Segvich, Dyann M.; Heiss, Christian; Ishihara, Mayumi; Azadi, Parastoo; Roach, Peter J.

2015-01-01

Glycogen is a branched polymer of glucose that acts as an energy reserve in many cell types. Glycogen contains trace amounts of covalent phosphate, in the range of 1 phosphate per 500–2000 glucose residues depending on the source. The function, if any, is unknown, but in at least one genetic disease, the progressive myoclonic epilepsy Lafora disease, excessive phosphorylation of glycogen has been implicated in the pathology by disturbing glycogen structure. Some 90% of Lafora cases are attributed to mutations of the EPM2A or EPM2B genes, and mice with either gene disrupted accumulate hyperphosphorylated glycogen. It is, therefore, of importance to understand the chemistry of glycogen phosphorylation. Rabbit skeletal muscle glycogen contained covalent phosphate as monoesters of C2, C3, and C6 carbons of glucose residues based on analyses of phospho-oligosaccharides by NMR. Furthermore, using a sensitive assay for glucose 6-P in hydrolysates of glycogen coupled with measurement of total phosphate, we determined the proportion of C6 phosphorylation in rabbit muscle glycogen to be ∼20%. C6 phosphorylation also accounted for ∼20% of the covalent phosphate in wild type mouse muscle glycogen. Glycogen phosphorylation in Epm2a−/− and Epm2b−/− mice was increased 8- and 4-fold compared with wild type mice, but the proportion of C6 phosphorylation remained unchanged at ∼20%. Therefore, our results suggest that C2, C3, and/or C6 phosphate could all contribute to abnormal glycogen structure or to Lafora disease. PMID:25416783

Single-Photon Emission Computed Tomography Is an Ambiguous Imaging Method on Initial Diagnosis for Acute Encephalopathy.

PubMed

Yamanaka, Gaku; Morishita, Nastumi; Oana, Shingo; Takeshita, Mika; Morichi, Shinichiro; Ishida, Yu; Kashiwagi, Yasuyo; Kawashima, Hisashi

2016-01-01

The distinction between acute encephalopathy (AE) and convulsive disorders with pyrexia may be problematic. We analyzed the clinical and laboratory features in 127 children who were admitted for suspected AE. They were categorized into (1) definite acute encephalopathy group (DAEG; n = 17, abnormal findings on electroencephalography [EEG], magnetic resonance imaging, or single-photon emission computed tomography [SPECT] with prolonged impaired consciousness), (2) probable acute encephalopathy group (PAEG; n = 21, abnormal findings without prolonged impaired consciousness), and (3) nonacute encephalopathy group (NAEG; n = 89). Cerebrospinal fluid interleukin-6 (CSF IL-6), and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase levels were significantly higher in DAEG compared with NAEG but not PAEG. No significant differences were observed between DAEG and PAEG except for serum creatinine levels. In PAEG, an area of hypoperfusion was observed on SPECT images of nine patients with normal CSF IL-6 levels. AE was suspected in two PAEG patients who exhibited high CSF IL-6 levels and abnormal EEG findings without abnormal SPECT findings. All seven patients with severe neurological sequelae were categorized to DAEG. CSF IL-6 and serum AST, ALT, and creatine kinase levels may be valid predictors of typical AE; prolonged impaired consciousness is an important sign of AE. However, SPECT may not be suitable for initial diagnosis of AE. Georg Thieme Verlag KG Stuttgart · New York.

Probiotics are helpful in hepatic encephalopathy: a meta-analysis of randomized trials.

PubMed

Saab, Sammy; Suraweera, Duminda; Au, Jennifer; Saab, Elena G; Alper, Tori S; Tong, Myron J

2016-07-01

Hepatic encephalopathy (HE) is a major complication of cirrhosis and is associated with decreased survival and increased health care utilization. The aim of this study was to evaluate the efficacy of probiotics in the management minimal hepatic encephalopathy HE (MHE) and overt HE (OHE) in comparison to no treatment/placebo and lactulose. The main outcomes measured were mortality, improvement in MHE, progression to OHE in patients with MHE and hospitalization. We calculated odds ratios (OR) with 95% confidence intervals (CI). Study heterogeneity was assessed using the I(2) statistic. Fourteen studies totalling 1152 patients were included in the analysis. The use of probiotics had no impact on the overall mortality when compared to either lactulose (OR: 1.07, 95% CI: 0.47-2.44, P = 0.88) or no treatment/placebo (OR: 0.69, 95% CI: 0.42-1.14, P = 0.15). When probiotics was compared to no treatment/placebo, it was associated with a significant improvement in MHE (OR: 3.91, 95% CI: 2.25-6.80, P < 0.00001), decreased hospitalization rates (OR: 0.53, 95% CI: 0.33-0.86, P = 0.01) and decreased progression to overt hepatic encephalopathy (OR: 0.40, 95% CI: 0.26-0.60, P < 0.0001). However when compared to lactulose, probiotics did not show a significant difference in improvement of MHE (OR: 0.81, 95% CI: 0.52-1.27, P = 0.35), hospitalization rates (OR: 1.02, 95% CI: 0.52-1.99, P = 0.96) or progression to overt hepatic encephalopathy (OR: 1.24, 95% CI 0.73-2.10, P = 0.42). Overall the use of probiotics was more effective in decreasing hospitalization rates, improving MHE and preventing progression to OHE in patients with underlying MHE than placebo, but similar to that seen with lactulose. The use of probiotics did not affect mortality rates. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

What is new about diet in hepatic encephalopathy.

PubMed

Merli, Manuela; Iebba, Valerio; Giusto, Michela

2016-12-01

There is a relationship between hepatic encephalopathy (HE) protein malnutrition and muscle wasting. Muscle may play an alternative role in ammonia detoxification. Molecular mechanisms responsible for muscle depletion are under investigation. Specific nutrients may interact to reverse the molecular pathways involved in muscle wasting at an early stage. Training exercises have also been proposed to improve skeletal muscle mass. However, these data refer to small groups of patients. The amelioration of muscle mass may potentially help to prevent HE. The pathogenesis of HE is associated with modifications of the gut microbiota and diet is emerging to play a relevant role in the modulation of the gut milieu. Vegetarian and fibre-rich diets have been shown to induce beneficial changes on gut microbiota in healthy people, with reduction of Bacteroides spp., Enterobacteriaceae, and Clostridium cluster XIVa bacteria. By way of contrast, it has been suggested that a high-fat or protein diet may increase Firmicutes and reduce Bacteroidetes phylum. Milk-lysozyme and milk-oligosaccharides have also been proposed to induce a "healthy" microbiota. At present, no studies have been published describing the modification of the gut microbiota in cirrhotic patients with HE as a response to specific diets. New research is needed to evaluate the potentiality of foods in the modulation of gut microbiota in liver disease and HE.

Noninvasive versus conventional ventilation to treat hypercapnic encephalopathy in chronic obstructive pulmonary disease.

PubMed

Scala, Raffaele; Nava, Stefano; Conti, Giorgio; Antonelli, Massimo; Naldi, Mario; Archinucci, Ivano; Coniglio, Giovanni; Hill, Nicholas S

2007-12-01

We recently reported a high success rate using noninvasive positive pressure ventilation (NPPV) to treat COPD exacerbations with hypercapnic encephalopathy. This study compared the hospital outcomes of NPPV vs. conventional mechanical ventilation (CMV) in COPD exacerbations with moderate to severe hypercapnic encephalopathy, defined by a Kelly score of 3 or higher. A 3-year prospective matched case-control study in a respiratory semi-intensive care unit (RSICU) and intensive care unit (ICU). From 103 consecutive patients the study included 20 undergoing NPPV and 20 CMV, matched for age, simplified acute physiology score II, and baseline arterial blood gases. ABG significantly improved in both groups after 2 h. The rate of complications was lower in the NPPV group than in the CMV group due to fewer cases of nosocomial pneumonia and sepsis. In-hospital mortality, 1-year mortality, and tracheostomy rates were similar in the two groups. Fewer patients remained on ventilation after 30 days in NPPV group. The NPPV group showed a shorter duration of ventilation. In COPD exacerbations with moderate to severe hypercapnic encephalopathy, the use of NPPV performed by an experienced team compared to CMV leads to similar short and long-term survivals with a reduced nosocomial infection rate and duration of ventilation.

De novo variants in RHOBTB2, an atypical Rho GTPase gene, cause epileptic encephalopathy.

PubMed

Belal, Hazrat; Nakashima, Mitsuko; Matsumoto, Hiroshi; Yokochi, Kenji; Taniguchi-Ikeda, Mariko; Aoto, Kazushi; Amin, Mohammed Badrul; Maruyama, Azusa; Nagase, Hiroaki; Mizuguchi, Takeshi; Miyatake, Satoko; Miyake, Noriko; Iijima, Kazumoto; Nonoyama, Shigeaki; Matsumoto, Naomichi; Saitsu, Hirotomo

2018-05-16

By whole exome sequencing, we identified three de novo RHOBTB2 variants in three patients with epileptic encephalopathies (EEs). Interestingly, all three patients showed acute encephalopathy (febrile status epilepticus), with magnetic resonance imaging revealing hemisphere swelling or reduced diffusion in various brain regions. RHOBTB2 encodes Rho-related BTB domain-containing protein 2, an atypical Rho GTPase that is a substrate-specific adaptor or itself is a substrate for the Cullin-3 (CUL3)-based ubiquitin/proteasome complex. Transient expression experiments in Neuro-2a cells revealed that mutant RHOBTB2 was more abundant than wild-type RHOBTB2. Co-expression of CUL3 with RHOBTB2 decreased the level of wild-type RHOBTB2 but not the level of any of the three mutants, indicating impaired CUL3 complex-dependent degradation of the three mutants. These data indicate that RHOBTB2 variants are a rare genetic cause of EEs, in which acute encephalopathy might be a characteristic feature, and that precise regulation of RHOBTB2 levels is essential for normal brain function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

PubMed Central

Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

2016-01-01

Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as “metronidazole induced encephalopathy”(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

The Vermont oxford neonatal encephalopathy registry: rationale, methods, and initial results

PubMed Central

2012-01-01

Background In 2006, the Vermont Oxford Network (VON) established the Neonatal Encephalopathy Registry (NER) to characterize infants born with neonatal encephalopathy, describe evaluations and medical treatments, monitor hypothermic therapy (HT) dissemination, define clinical research questions, and identify opportunities for improved care. Methods Eligible infants were ≥ 36 weeks with seizures, altered consciousness (stupor, coma) during the first 72 hours of life, a 5 minute Apgar score of ≤ 3, or receiving HT. Infants with central nervous system birth defects were excluded. Results From 2006–2010, 95 centers registered 4232 infants. Of those, 59% suffered a seizure, 50% had a 5 minute Apgar score of ≤ 3, 38% received HT, and 18% had stupor/coma documented on neurologic exam. Some infants experienced more than one eligibility criterion. Only 53% had a cord gas obtained and only 63% had a blood gas obtained within 24 hours of birth, important components for determining HT eligibility. Sixty-four percent received ventilator support, 65% received anticonvulsants, 66% had a head MRI, 23% had a cranial CT, 67% had a full channel encephalogram (EEG) and 33% amplitude integrated EEG. Of all infants, 87% survived. Conclusions The VON NER describes the heterogeneous population of infants with NE, the subset that received HT, their patterns of care, and outcomes. The optimal routine care of infants with neonatal encephalopathy is unknown. The registry method is well suited to identify opportunities for improvement in the care of infants affected by NE and study interventions such as HT as they are implemented in clinical practice. PMID:22726296

Covert Hepatic Encephalopathy: Can My Patient Drive?

PubMed Central

Shaw, Jawaid; Bajaj, Jasmohan S

2016-01-01

Liver cirrhosis is a public health problem and hepatic encephalopathy (HE) is one of its main complications, which can be either overt meaning thereby evident and readily diagnosed, or covert/minimal (CHE) needing psychometric testing for diagnosis. Patients with CHE hepatic encephalopathy have deficits in multiple domains including visuo-spatial assessment, attention, response inhibition, working memory, along with psychomotor speed to name a few areas. These patients have poor navigational skills, get fatigued easily and demonstrate poor insight into their driving deficits. The combination of all these leads them to have poor driving skills leading to traffic violations and crashes as demonstrated not only on the simulation testing but also in real life driving events. There are multiple psychometric tests for CHE testing but these are not easily available and there is no uniform consensus on the gold standard testing as of yet. It does not automatically connote that all patients who test positive on driving simulation testing are unfit to drive. The physicians are encouraged to take driving history from the patient and the care- givers on every encounter and focus their counseling efforts more on patients with recent history of traffic crashes, with abnormal simulation studies and history of alcohol cessation within last year. As physicians are not trained to determine fitness to drive, their approach towards CHE patients in regards to driving restrictions should be driven by ethical principles while as respecting the local laws. PMID:28027071

Cerebral glucose deficiency versus oxygen deficiency in neonatal encephalopathy.

PubMed

Rudolph, A M

2018-04-24

Hypoxic-ischemic encephalopathy (HIE) in newborn infants is generally considered to result from decreased arterial oxygen content or cerebral blood flow. Cerebral injury similar to that of HIE has been noted with hypoglycemia. Studies in fetal lambs have shown that ventilation with 3% oxygen did not change cerebral blood flow, but ventilation with 100% oxygen resulted in marked reduction in cerebral blood flow, glucose delivery and glucose consumption. Blood glucose concentration falls markedly after birth; this, associated with the fall in cerebral blood flow, greatly reduces glucose supply to the brain. In preterm infants, blood glucose levels tend to be very low. Also persistent patency of the ductus arteriosus may reduce cerebral flow in diastole, thus exaggerating the decrease in glucose supply. I propose that glycopenic-ischemic encephalopathy is a more appropriate term for the cerebral insult. We should consider more aggressive management of the low blood glucose concentrations in the neonate, and particularly in preterm infants. Administration of high levels of oxygen in inspired air should be avoided to reduce the enhancement of cerebral vasoconstriction and decreased flow that normally occurs after birth.

Early-onset seizures due to mosaic exonic deletions of CDKL5 in a male and two females.

PubMed

Bartnik, Magdalena; Derwińska, Katarzyna; Gos, Monika; Obersztyn, Ewa; Kołodziejska, Katarzyna E; Erez, Ayelet; Szpecht-Potocka, Agnieszka; Fang, Ping; Terczyńska, Iwona; Mierzewska, Hanna; Lohr, Naomi J; Bellus, Gary A; Reimschisel, Tyler; Bocian, Ewa; Mazurczak, Tadeusz; Cheung, Sau Wai; Stankiewicz, Paweł

2011-05-01

Mutations in the CDKL5 gene have been associated with an X-linked dominant early infantile epileptic encephalopathy-2. The clinical presentation is usually of severe encephalopathy with refractory seizures and Rett syndrome (RTT)-like phenotype. We attempted to assess the role of mosaic intragenic copy number variation in CDKL5. We have used comparative genomic hybridization with a custom-designed clinical oligonucleotide array targeting exons of selected disease and candidate genes, including CDKL5. We have identified mosaic exonic deletions of CDKL5 in one male and two females with developmental delay and medically intractable seizures. These three mosaic changes represent 60% of all deletions detected in 12,000 patients analyzed by array comparative genomic hybridization and involving the exonic portion of CDKL5. We report the first case of an exonic deletion of CDKL5 in a male and emphasize the importance of underappreciated mosaic exonic copy number variation in patients with early-onset seizures and RTT-like features of both genders.

Posterior reversible encephalopathy syndrome as a complication of Henoch-Schönlein purpura in a seven-year-old girl.

PubMed

Dos Santos, Daiane; Langer, Felipe Welter; Dos Santos, Tatiane; Rafael Tronco Alves, Giordano; Feiten, Marisa; Teixeira de Paula Neto, Walter

2017-02-01

Introduction Henoch-Schönlein purpura is a multisystem small vessel vasculitis. Neurologic manifestations are uncommon. Posterior reversible encephalopathy syndrome is a rare complication of Henoch-Schönlein purpura with typical clinical and neuroimaging findings that occurs most commonly in the setting of severe hypertension and renal injury. Case presentation A seven-year-old girl was admitted to our institution presenting with clinical and laboratory findings suggestive of Henoch-Schönlein purpura. Glucocorticoid therapy was initiated, but five days following her admission, she developed altered consciousness, seizures, arterial hypertension, and cortical blindness. Brain MRI scan revealed areas of vasogenic oedema in parieto-occipital lobes, consistent with posterior reversible encephalopathy syndrome. She was immediately initiated on antihypertensives and antiepileptics, which successfully improved her neurologic symptoms. Further laboratory work-up disclosed a rapidly progressive glomerulonephritis secondary to Henoch-Schönlein purpura that was the likely cause of her sudden blood pressure elevation. Immunosuppressive therapy was undertaken, and at one-year follow-up, the patient exhibited complete renal and neurologic recovery. Conclusion Posterior reversible encephalopathy syndrome is a severe complication of Henoch-Schönlein purpura. If promptly diagnosed and treated, children with Henoch-Schönlein purpura presenting with posterior reversible encephalopathy syndrome usually have a good prognosis. Clinicians should be familiar with the characteristic presentation of posterior reversible encephalopathy syndrome and be aware that hypertension and renal injury may predispose Henoch-Schönlein purpura patients to developing this complication.

Detection frequency of human herpesviruses-6A, -6B, and -7 genomic sequences in central nervous system DNA samples from post-mortem individuals with unspecified encephalopathy.

PubMed

Chapenko, Svetlana; Roga, Silvija; Skuja, Sandra; Rasa, Santa; Cistjakovs, Maksims; Svirskis, Simons; Zaserska, Zane; Groma, Valerija; Murovska, Modra

2016-08-01

In this autopsy-based study, human herpesvirus-6 (HHV-6) and -7 (HHV-7) genomic sequence frequency, HHV-6 variants, HHV-6 load and the expression of HHV-6 antigens in brain samples from the individuals, with and without unspecified encephalopathy (controls), using nested and real-time polymerase chain reactions, restriction endonuclease, and immunohistochemical analysis were examined. GraphPad Prism 6.0 Mann-Whitney nonparametric and chi-square test and Fisher's exact test were used for statistical analysis. The encephalopathy diagnoses were shown by magnetic resonance imaging made during their lifetime and macro- and microscopically studied autopsy tissue materials. Widespread HHV-6 and/or HHV-7 positivity was detected in the brain tissue of various individuals with encephalopathy, as well as in controls (51/57, 89.4 % and 35/51, 68.6 %, respectively; p = 0.009). Significantly higher detection frequency of single HHV-6 and concurrent HHV-6 + HHV-7 DNA was found in pia mater meninges, frontal lobe, temporal lobe, and olfactory tract DNAs in individuals with encephalopathy compared to the control group. HHV-6 load and higher frequency of the viral load >10 copies/10(6) cells significantly differed in samples from individuals with and without encephalopathy. The expression of HHV-6 antigens was revealed in different neural cell types with strong predominance in the encephalopathy group. In all HHV-6-positive autopsy samples of individuals with and without encephalopathy, HHV-6B was revealed. Significantly higher detection frequency of beta-herpesvirus DNA, more often detected HHV-6 load >10 copies/10(6) cells, as well as the expression of HHV-6 antigens in different brain tissue samples from individuals with encephalopathy in comparison with control group indicate on potential involvement of these viruses in encephalopathy development.

Clinical and neuroimaging profile of HIV-1 encephalopathy in infancy and childhood in a sub-Saharan African country.

PubMed

G Mariam, Ayle; Assefa, Getachew

2012-10-01

Neurological dysfunction in AIDS is common, occurring in as many as eighty percent of children. Thus, it is important to recognize the central nervous system imaging appearance of HIV, in particular those of HIV encephalopathy, as this is an AIDS defining illness and with distinct neuro-imaging features essential for early diagnosis and timely therapeutic intervention To identify the clinical features in HIV-1 infection of the central nervous system and their associated neuroradiological correlates. Retrospective review of the records of all children with HIV-1 encephalopathy identified among children with neurological and developmental problems and who were on follow up at a child development and neurology clinic in an African city. A total of 22 children (10 male and 12 female) with HIV-1 encephalopathy were identified among 2382 children with various forms of neurological and developmental problems and who were on follow up at a child development and neurology clinic for a little bit over eight years period. All the children acquired the infection vertically. The age range of these children was between 10 months to 14 years. The median age was 5.6 years. The mean duration of symptom was 3.2 years. Global delay or regression in development along with signs of pyramidal tract involvement and seizures were the commonest clinical signs observed in these children. Neuro-behavioral problems were commonly observed among preschool and school aged children. In older children and preadolescents focal seizures with or with out neurologic deficit and neuroradiological findings were common. Nonhemorrhagic stroke was rare and occurred in one child and another child had cortical blindness. Three children had no neurological deficit. Rapid progression of the disease carried grave prognosis. Opportunistic infections and tumors of the central nervous system were also uncommon among these children. Brain volume loss with dilatation of the lateral ventricle, bilateral symmetrical

Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

PubMed

Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo

2015-02-01

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.

Vogt-Koyanagi-Harada syndrome presenting with encephalopathy

PubMed Central

Naeini, Alireza E.; Daneshmand, Dana; Khorvash, Farzin; Chitsaz, Ahmad

2013-01-01

VogtKoyanagi-Harada (VKH) is a rare syndrome affecting tissues with melanocytes. The possibility that VKH syndrome has an autoimmune pathogenesis is supported by the high frequency of human leukocyte antigen-DR4 commonly associated with other autoimmune diseases. Eyes are the main affected organ, resulting in blindness. Brain disease as a late onset event is extremely rare. Here, we are reporting a 57-year-old woman with previously diagnosed VKH syndrome, presenting with a late-onset brain encephalopathy. She was treated with corticosteroids and discharged from hospital with good general condition. PMID:23956579

The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies.

PubMed

Mathis, Déborah; Abela, Lucia; Albersen, Monique; Bürer, Céline; Crowther, Lisa; Beese, Karin; Hartmann, Hans; Bok, Levinus A; Struys, Eduard; Papuc, Sorina M; Rauch, Anita; Hersberger, Martin; Verhoeven-Duif, Nanda M; Plecko, Barbara

2016-09-01

Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B6-dependent epilepsy. As these defects interfere with vitamin B6 metabolism by different mechanisms, the plasma vitamin B6 profile can give important clues for further molecular work-up. This has so far been investigated in only a small number of patients. We evaluated the vitamin B6 vitamers pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN) and the catabolite pyridoxic acid (PA) in the so far largest patient cohort: reference (n = 50); pyridox(am)ine 5'-phosphate oxidase (PNPO) deficiency (n = 6); antiquitin (ATQ) deficiency (n = 21); tissue non-specific alkaline phosphatase (TNSALP) deficiency (n = 2) and epileptic encephalopathy (EE) of unknown etiology tested negative for ATQ and PNPO deficiency (n = 64). High plasma PM concentration was found in all patients with PNPO deficiency irrespective of vitamin B6 supplementation. Their PM concentration and the PM/PA ratio was significantly higher (p < 0.0001), compared to any other patients analysed. One patient with TNSALP deficiency and sampling prior to PN supplementation had markedly elevated plasma PLP concentration. On PN supplementation, patients with TNSALP deficiency, ATQ deficiency and patients of the EE cohort had similar plasma vitamin B6 profiles that merely reflect the intake of supra-physiological doses of vitamin B6. The interval of sampling to the last PN intake strongly affected the plasma concentrations of PN, PL and PA. PM concentrations and the PM/PA ratio clearly separated PNPO-deficient patients from the other cohorts. The plasma PM/PA ratio thus represents a robust biomarker for the selective screening of PNPO deficiency.

Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage Gated Potassium Channel Mediated Seizures

PubMed Central

Sirsi, Deepa; Dolce, Alison; Greenberg, Benjamin M; Thodeson, Drew

2017-01-01

Background There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis. Patient Description We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization. Conclusion This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes. PMID:29308451

Leigh-like encephalopathy complicating Leber's hereditary optic neuropathy.

PubMed

Funalot, Benoît; Reynier, Pascal; Vighetto, Alain; Ranoux, Danièle; Bonnefont, Jean-Paul; Godinot, Catherine; Malthièry, Yves; Mas, Jean-Louis

2002-09-01

Leber's hereditary optic neuropathy is a mitochondrial disease caused by point mutations in mitochondrial DNA. It usually presents as severe bilateral visual loss in young adults. We report on a neurological disorder resembling Leigh syndrome, which complicated Leber's hereditary optic neuropathy in three unrelated male patients harboring mitochondrial DNA mutations at nucleotide positions 3460, 14459, and 14484, respectively. This Leigh-like encephalopathy appears to be associated with a much more severe outcome than isolated Leber's hereditary optic neuropathy.

Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction.

PubMed

Milev, Miroslav P; Grout, Megan E; Saint-Dic, Djenann; Cheng, Yong-Han Hank; Glass, Ian A; Hale, Christopher J; Hanna, David S; Dorschner, Michael O; Prematilake, Keshika; Shaag, Avraham; Elpeleg, Orly; Sacher, Michael; Doherty, Dan; Edvardson, Simon

2017-08-03

Progressive childhood encephalopathy is an etiologically heterogeneous condition characterized by progressive central nervous system dysfunction in association with a broad range of morbidity and mortality. The causes of encephalopathy can be either non-genetic or genetic. Identifying the genetic causes and dissecting the underlying mechanisms are critical to understanding brain development and improving treatments. Here, we report that variants in TRAPPC12 result in progressive childhood encephalopathy. Three individuals from two unrelated families have either a homozygous deleterious variant (c.145delG [p.Glu49Argfs ∗ 14]) or compound-heterozygous variants (c.360dupC [p.Glu121Argfs ∗ 7] and c.1880C>T [p. Ala627Val]). The clinical phenotypes of the three individuals are strikingly similar: severe disability, microcephaly, hearing loss, spasticity, and characteristic brain imaging findings. Fibroblasts derived from all three individuals showed a fragmented Golgi that could be rescued by expression of wild-type TRAPPC12. Protein transport from the endoplasmic reticulum to and through the Golgi was delayed. TRAPPC12 is a member of the TRAPP protein complex, which functions in membrane trafficking. Variants in several other genes encoding members of the TRAPP complex have been associated with overlapping clinical presentations, indicating shared and distinct functions for each complex member. Detailed understanding of the TRAPP-opathies will illuminate the role of membrane protein transport in human disease. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy.

PubMed

Carreras, Nuria; Alsina, Miguel; Alarcon, Ana; Arca-Díaz, Gemma; Agut, Thais; García-Alix, Alfredo

To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4±1.4°C and mean transfer time was 3.3±2.0h. Mean age at arrival was 5.6±2.5h. Temperature at arrival was between 33 and 35°C in 41 (61%) infants, between 35°C and 36.5°C in 15 (22%) and <33°C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature<33°C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p<0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves' Disease: Case Report and Review of the Literature.

PubMed

Tsironis, Theocharis; Tychalas, Athanasios; Kiourtidis, Dimitrios; Kountouras, Jannis; Xiromerisiou, Georgia; Rudolf, Jobst; Deretzi, Georgia

2017-07-01

Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves' disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves' encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before. We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves' disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically. To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves' disease, thereby underscoring the necessity of suspicion of possible underlying Graves' disease in patients with acute paralysis and encephalopathy of unclear origin.

Kv7.3 Compound Heterozygous Variants in Early Onset Encephalopathy Reveal Additive Contribution of C-Terminal Residues to PIP2-Dependent K+ Channel Gating.

PubMed

Ambrosino, Paolo; Freri, Elena; Castellotti, Barbara; Soldovieri, Maria Virginia; Mosca, Ilaria; Manocchio, Laura; Gellera, Cinzia; Canafoglia, Laura; Franceschetti, Silvana; Salis, Barbara; Iraci, Nunzio; Miceli, Francesco; Ragona, Francesca; Granata, Tiziana; DiFrancesco, Jacopo C; Taglialatela, Maurizio

2018-01-30

Over one hundred mutations in the Kv7.2 (KCNQ2) gene encoding for phosphatidylinositol 4,5-bisphosphate (PIP 2 )-sensitive voltage-gated K + channel subunits have been identified in early-onset epilepsies with wide phenotypic variability. By contrast, only few mutations in the closely related Kv7.3 (KCNQ3) gene have been reported, mostly associated with typical benign familial neonatal seizures (BFNS). We herein describe a patient affected by early onset epileptic encephalopathy (EOEE) carrying two Kv7.3 missense mutations (p.Val359Leu/V359L and p.Asp542Asn/D542N) in compound heterozygosis, each inherited from an asymptomatic parent. Patch-clamp recordings from transiently transfected CHO cells showed that, when incorporated in physiologically relevant Kv7.2 + Kv7.3 heteromeric channels, expression of Kv7.3 V359L or Kv7.3 D542N subunits failed to affect current density, whereas a significant decrease was instead observed when these mutant subunits were both simultaneously present. Modeling and functional experiments revealed that each variant decreased PIP 2 -dependent current regulation, with additive effects when the two were co-expressed. Moreover, expression of Kv7.2 subunits carrying the D535N variant previously described in three sporadic EOEE cases prompted functional changes more dramatic when compared to those of the corresponding D542N variant in Kv7.3, but similar to those observed when both Kv7.3 V359L and Kv7.3 D542N subunits were expressed together. Finally, the Kv7 activator retigabine restored channel dysfunction induced by each Kv7.2 or Kv7.3 variant(s). These results provide a plausible molecular explanation for the apparent recessive inheritance of the phenotype in the family investigated, and a rational basis for personalized therapy with Kv7 channel activators in EOEE patients carrying loss-of-function mutations in Kv7.2 or Kv7.3.

Can Lactobacillus acidophilus improve minimal hepatic encephalopathy? A neurometabolite study using magnetic resonance spectroscopy.

PubMed

Ziada, Dina H; Soliman, Hanan H; El Yamany, Saher A; Hamisa, Manal F; Hasan, Azza M

2013-09-01

Minimal hepatic encephalopathy (MHE) is diagnosed when hepatic patients perform worse on psychometric tests compared to healthy controls. This study aimed to evaluate probiotics as alternative therapy in MHE. This is an open-label randomised controlled trial, performed in the Department of Tropical Medicine and Infectious Diseases, Tanta University Hospitals, from March 2010 to January 2012. A total of 90 patients with MHE were allocated by simple randomisation to three parallel equal groups. Group A received lactulose, group B a probiotic (Lactobacillus acidophilus) and group C served as the control. After informed consent, patients were tested for gut micrecology, fasting blood ammonia, liver functions and magnetic resonance spectroscopy (MRS) examination to study brain metabolites, mainly choline (Cho), myo-inositol (mI), glutamine+glutamate (Glx) and creatinin (Cre). Patients who developed overt encephalopathy were excluded from analysis. The whole battery of investigations was repeated in the same order after 4weeks. The probiotic was better tolerated than lactulose. The relative risk reduction (RRR) of developing overt encephalopathy was 60% in the case of lactulose and 80% in the case of probiotic, with a number needed to treat (NNT) of 2.4 and 2.3, respectively. The differential but not total microecology count was significantly shifted towards saccharolytic rather than proteolytic bacteria. The mI/Cre and (Cho+mI)/Glx ratios were significantly increased and the Glx/Cre ratio was significantly reduced after 1month-follow-up in the probiotic group compared to the lactulose group and in both treatment groups compared to the control group. Both probiotic and lactulose therapy can improve blood ammonia and psychometric tests in MHE and reduce the risk of developing overt encephalopathy. MRS showed more improvement in the levels of brain neurometabolites in the probiotic group. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All

Clinical Seizures in Neonatal Hypoxic-Ischemic Encephalopathy Have No Independent Impact on Neurodevelopmental Outcome: Secondary Analyses of Data from the Neonatal Research Network Hypothermia Trial

PubMed Central

Kwon, Jennifer M.; Guillet, Ronnie; Shankaran, Seetha; Laptook, Abbot R.; McDonald, Scott A.; Ehrenkranz, Richard A.; Tyson, Jon E.; O'Shea, T. Michael; Goldberg, Ronald N.; Donovan, Edward F.; Fanaroff, Avroy A.; Poole, W. Kenneth; Higgins, Rosemary D.; Walsh, Michele C.

2012-01-01

It remains controversial as to whether neonatal seizures have additional direct effects on the developing brain separate from the severity of the underlying encephalopathy. Using data collected from infants diagnosed with hypoxic-ischemic encephalopathy, and who were enrolled in an National Institute of Child Health and Human Development trial of hypothermia, we analyzed associations between neonatal clinical seizures and outcomes at 18 months of age. Of the 208 infants enrolled, 102 received whole body hypothermia and 106 were controls. Clinical seizures were generally noted during the first 4 days of life and rarely afterward. When adjustment was made for study treatment and severity of encephalopathy, seizures were not associated with death, or moderate or severe disability, or lower Bayley Mental Development Index scores at 18 months of life. Among infants diagnosed with hypoxic-ischemic encephalopathy, the mortality and morbidity often attributed to neonatal seizures can be better explained by the underlying severity of encephalopathy. PMID:20921569

Conservative management of severe serotonin syndrome with coma, myoclonus, and crossed-extensor reflex complicated by hepatic encephalopathy.

PubMed

Ramachandran, Vignesh; Ding, Belicia; George, Rollin; Novakovic, Matthew

2018-01-01

Serotonin syndrome (SS) is an underrecognized and potentially fatal disorder that occurs secondary to combinational use or overdose of a single serotonergic medication. The presentation may be complicated by hepatic encephalopathy in cirrhotic patients, which may also affect metabolism of these serotonergic agents. The authors report a rare case of severe SS complicated by hepatic encephalopathy secondary to cirrhosis in a 52-year-old woman after an increase in her home dosage of fluoxetine and addition of other psychiatric medications.

A new mtDNA mutation in the tRNA[sup Lys] gene associated with myoclonic epilepsy and ragged-red fibers (MERRF)

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

Silvestri, G.; Moraes, C.T.; Shanske, S.

1992-12-01

Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A[r arrow]G transition at mtDNA nt 8344, within a conserved region of the tRNA[sup Lys] gene. Although the 8344 mutation is highly prevalent in patients with MERRF, it is not observed in 10%-20% of the cases, suggesting genetic heterogeneity. The authors have sequenced the tRNA[sup Lys] gene of five MERRF patients lacking the common 8344 mutation. One of these showed a novel T[r arrow]C transition at nucleotide position 8356, disrupting a highly conserved base pair in the T[Psi]C stem. The mutant mtDNA population was essentially homoplasmic in muscle butmore » was heteroplasmic in blood (47%). Neither 20 patients with other mitochondrial diseases nor 25 controls carried this mutation. These findings suggest that tRNA[sup Lys] alterations may play a specific role in the pathogenesis of MERRF syndrome. 21 refs., 4 figs.« less

[Mental illness, personality traits and quality of life in epilepsy: control study of patients with juvenile myoclonic epilepsy and other epilepsies].

PubMed

Martínez-Domínguez, Sara; Labrada-Abella, Jacob; Pedrós-Roselló, Alfonso; López-Gomáriz, Elena; Tenías-Burillo, José M

2013-06-16

The association of epilepsy with mental illness is described for years. Current is trying to relate certain epilepsies, such as juvenile myoclonic epilepsy (JME) with certain personality traits marked by emotional instability. We study a group of patients with JME and his mental state, with emphasis on the personality traits, presence of clinical anxiety or depression and quality of life, with other epilepsy patients versus a control group. Patients with epilepsy have more marked personality traits and symptoms of anxiety and depression, making a more negative assessment of their quality of life than the control group. Patients with others epilepsy have a higher other personality disorder and a poorer perception of their quality of life than patients with JME. Differences are obtained among patients with epilepsy and control groups in all the variables analyzed (personality, anxiety, depression and quality of life). JME patients have better scores on personality and quality of life than those in the other group of epilepsies.

Emotion-induced myoclonic absence-like seizures in a patient with inv-dup(15) syndrome: a clinical, EEG, and molecular genetic study.

PubMed

Aguglia, U; Le Piane, E; Gambardella, A; Messina, D; Russo, C; Sirchia, S M; Porta, G; Quattrone, A

1999-09-01

We have described a clinical EEG and molecular genetic study of a 9-year-old boy with inv-dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5-20 s after the onset of repeated cheek-kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence-like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11-q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral gamma-aminobutyric acid (GABA)-mediated inhibition accounts for the severe epilepsy that we observed in this patient.

An Atypical Presentation of Subacute Encephalopathy with Seizures in Chronic Alcoholism Syndrome.

PubMed

Kim, Tae-Kyoung; Jung, Eui Sung; Park, Jong-Moo; Kang, Kyusik; Lee, Woong-Woo; Lee, Jung-Ju

2016-06-01

Subacute encephalopathy with seizures in chronic alcoholism syndrome is a rare clinical manifestation in patients with chronic alcohol abuse. We report the case of a patient with chronic alcoholism who presented with partial nonconvulsive status epilepticus associated with a thalamic lesion.

Improvement of Cerebral Hypoperfusion with Levothyroxine Therapy in Hashimoto's Encephalopathy Demonstrated by 99mTc-HMPAO-SPECT

PubMed Central

Schnedl, Wolfgang J.; Mirzaei, Siroos; Wallner-Liebmann, Sandra J.; Tafeit, Erwin; Mangge, Harald; Krause, Robert; Lipp, Rainer W.

2013-01-01

Background Hashimoto's encephalopathy (HE) is a rare immune-mediated encephalopathy associated with autoimmune Hashimoto's thyroiditis. Objectives and Methods We report on a patient with HE and significant clinical improvement correlating with an increase in cerebral blood flow demonstrated by hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). HMPAO-SPECT was performed with 740 MBq of technetium-99m-HMPAO. To demonstrate the improvement in regional cerebral blood flow, individual regions of interest were drawn around visually diminished HMPAO uptake, the lesion to reference region ratio was calculated and transverse section images and semi-quantitative measurements were performed. Results We show a 5-year follow-up with significant clinical improvement, a 10-fold reduction in autoantibodies to thyroid peroxidase and an approximately 20% improvement in cerebral blood flow with HMPAO-SPECT. Conclusion Adequate levothyroxine treatment achieving and maintaining euthyroidism should be considered as therapy to lower autoantibodies and improve clinical outcome in patients with Hashimoto's thyroiditis and encephalopathy. PMID:24783049

Spectral Electroencephalogram Analysis for the Evaluation of Encephalopathy Grade in Children With Acute Liver Failure.

PubMed

Press, Craig A; Morgan, Lindsey; Mills, Michele; Stack, Cynthia V; Goldstein, Joshua L; Alonso, Estella M; Wainwright, Mark S

2017-01-01

Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure. Retrospective cohort study. Tertiary care pediatric hospital. Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU. None. Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative β, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p < 0.03). Electroencephalograms from 33 patients with acute liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p < 0.006). Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p < 0.05). Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p < 0.025). Moderate to severe hepatic encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p

Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy.

PubMed

Eckman, Elizabeth A; Pacheco-Quinto, Javier; Herdt, Aimee R; Halperin, John J

2018-01-11

Lyme encephalopathy, characterized by non-specific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to CNS infection. Identical symptoms occur in innumerable other inflammatory states and may reflect the effect of systemic immune mediators on the CNS. Multiplex immunoassays were used to characterize the inflammatory profile in serum and CSF from Lyme and non-Lyme patients with a range of symptoms to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. CSF CXCL13 was elevated dramatically in confirmed neuroborreliosis (n=8) and to a lesser extent in possible neuroborreliosis (n=11) and other neuroinflammatory conditions (n=44). Patients with Lyme (n=63) or non-Lyme (n=8) encephalopathy had normal CSF findings, but had elevated serum levels of IL-7, TSLP, IL-17A, IL-17F, and MIP-1α/CCL3. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody (ITAb) production. However, CXCL13 does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory ITAb, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Contrast-induced encephalopathy following cardiac catheterization.

PubMed

Spina, Roberto; Simon, Neil; Markus, Romesh; Muller, David Wm; Kathir, Krishna

2017-08-01

To describe the epidemiology, pathophysiology, clinical presentation, and management of contrast-induced encephalopathy (CIE) following cardiac catheterization. CIE is an acute, reversible neurological disturbance directly attributable to the intra-arterial administration of iodinated contrast medium. The PubMed database was searched and all cases in the literature were retrieved and reviewed. 52 reports of CIE following cardiac catheterization were found. Encephalopathy, motor and sensory disturbances, vision disturbance, opthalmoplegia, aphasia, and seizures have been reported. Transient cortical blindness is the most commonly reported neurological syndrome, occurring in approximately 50% of cases. The putative mechanism involves disruption of the blood brain barrier and direct neuronal injury. Contrast-induced transient vasoconstriction has also been implicated. Symptoms typically appear within minutes to hours of contrast administration and resolve entirely within 24-48 hr. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts, and previous adverse reaction to iodinated contrast. Characteristic findings on cerebral imaging include cortical and sub-cortical contrast enhancement on computed tomography (CT). Imaging findings in CIE may mimic subarachnoid hemorrhage or cerebral ischemia; the Hounsfield scale on CT and the apparent diffusion coefficient on magnetic resonance imaging (MRI) are useful imaging tools in distinguishing these entities. In some cases, brain imaging is normal. Prognosis is excellent with supportive management alone. CIE tends to recur, although re-challenge with iodinated contrast without adverse effects has been documented. CIE is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterization. Given that prognosis is

Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

NASA Astrophysics Data System (ADS)

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.

Nano optical sensor binuclear Pt-2-pyrazinecarboxylic acid -bipyridine for enhancement of the efficiency of 3-nitrotyrosine biomarker for early diagnosis of liver cirrhosis with minimal hepatic encephalopathy.

PubMed

Attia, M S; Al-Radadi, Najlaa S

2016-12-15

A new, precise, and very selective method for increasing the impact and assessment of 3-nitrotyrosine (3-Nty) as a biomarker for early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE) disease was developed. The method depends on the formation of the ion pair associate between 3-nitrotyrosine and the optical sensor binuclear Pt-2-pyrazinecarboxylic acid (pca)-Bipyridine (bpy) complex doped in sol-gel matrix in buffer solution of pH 7.3. The binuclear Pt (pca)(bpy) has +II net charge which is very selective and sensitive for [3-Nty](-2) at pH 7.3 in serum sample of liver cirrhosis with MHE diseases. 3-nitrotyrosine (3-Nty) quenches the luminescence intensity of the nano optical sensor binuclear Pt(pca) (bpy) at 528nm after excitation at 370nm, pH 7.3. The remarkable quenching of the luminescence intensity at 528nm of nano binuclear Pt(pca) (bpy) doped in sol-gel matrix by various concentrations of the 3-Nty was successfully used as an optical sensor for the assessment of 3-Nty in different serum samples of (MHE) in patients with liver cirrhosis. The calibration plot was achieved over the concentration range 1.85×10(-5) - 7.95×10(-10)molL(-1) 3-Nty with a correlation coefficient of (0.999) and a detection limit of (4.7×10(-10)molL(-1)). The method increases the sensitivity (93.75%) and specificity (96.45%) of 3-Nty as a biomarker for early diagnosis of liver cirrhosis with MHE in patients. Copyright © 2016 Elsevier B.V. All rights reserved.

78 FR 72859 - Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2013-0064] Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice. SUMMARY: We are advising the public of our preliminary concurrence...

Posterior reversible encephalopathy with late postpartum eclampsia and short-term memory loss: a case report.

PubMed

Gimovsky, Martin L; Guzman, Guillermo M; Koscica, Karen L; Nazir, Munir A; Ross, Diane E

2010-01-01

Late postpartum eclampsia is more frequently recognized than past reports indicate. This report describes the association of a reversible encephalopathy in a woman with late postpartum eclampsia. A woman with lupus nephritis presented 7 days postpartum with eclampsia. Postseizure findings included dramatic short-term memory loss. Although a computed tomography scan was negative, subsequent magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) demonstrated vascular changes associated with a reversible encephalopathy. Conservative treatment with analeptic and antihypertensive therapy allowed a rapid resolution of all symptomatology. In women with eclampsia and unusual neurologic findings, an MRI/MRA may be useful even in the presence of a negative computed tomography scan.

Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias.

PubMed

Lichter-Konecki, Uta; Nadkarni, Vinay; Moudgil, Asha; Cook, Noah; Poeschl, Johannes; Meyer, Michael T; Dimmock, David; Baumgart, Stephen

2013-08-01

Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely. Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5°C±1°C for 72h, they were then slowly rewarmed by 0.5°C every 3h over 18h. In addition data of age-matched historic controls were collected for comparison. Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension. Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was

CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature.

PubMed

Lilles, Stella; Talvik, Inga; Noormets, Klari; Vaher, Ulvi; Õunap, Katrin; Reimand, Tiia; Sander, Valentin; Ilves, Pilvi; Talvik, Tiina

2016-12-01

Cyclin-dependent kinase-like 5 ( CDKL5 ) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future. Georg Thieme Verlag KG Stuttgart · New York.

Curved reformat of the paediatric brain MRI into a 'flat-earth map' - standardised method for demonstrating cortical surface atrophy resulting from hypoxic-ischaemic encephalopathy.

PubMed

Simpson, Ewan; Andronikou, Savvas; Vedajallam, Schadie; Chacko, Anith; Thai, Ngoc Jade

2016-09-01

Hypoxic-ischaemic encephalopathy is optimally imaged with brain MRI in the neonatal period. However neuroimaging is often also performed later in childhood (e.g., when parents seek compensation in cases of alleged birth asphyxia). We describe a standardised technique for creating two curved reconstructions of the cortical surface to show the characteristic surface changes of hypoxic-ischaemic encephalopathy in children imaged after the neonatal period. The technique was applied for 10 cases of hypoxic-ischaemic encephalopathy and also for age-matched healthy children to assess the visibility of characteristic features of hypoxic-ischaemic encephalopathy. In the abnormal brains, fissural or sulcal widening was seen in all cases and ulegyria was identifiable in 7/10. These images could be used as a visual aid for communicating MRI findings to clinicians and other interested parties.

Biomarkers of multiorgan injury in neonatal encephalopathy.

PubMed

Aslam, Saima; Molloy, Eleanor J

2015-01-01

Neonatal encephalopathy (NE) is a major contributor to neurodevelopmental deficits including cerebral palsy in term and near-term infants. The long-term neurodevelopmental outcome is difficult to predict with certainty in first few days of life. Multiorgan involvement is common but not part of the diagnostic criteria for NE. The most frequently involved organs are the heart, liver, kidneys and hematological system. Cerebral and organ involvement is associated with the release of organ specific biomarkers in cerebrospinal fluid, urine and blood. These biomarkers may have a role in the assessment of the severity of asphyxia and long-term outcome in neonates with NE.

White matter injury in term newborns with neonatal encephalopathy.

PubMed

Li, Amanda M; Chau, Vann; Poskitt, Kenneth J; Sargent, Michael A; Lupton, Brian A; Hill, Alan; Roland, Elke; Miller, Steven P

2009-01-01

White matter injury (WMI) is the characteristic pattern of brain injury detected on magnetic resonance imaging in the premature newborn. Focal noncystic WMI is increasingly recognized in populations of term newborns. The aim of this study was to describe the occurrence of focal noncystic WMI in a cohort of 48 term newborns with encephalopathy studied with magnetic resonance imaging at 72 +/- 12 h of life, and to identify clinical risk factors for this pattern of injury. Eleven newborns (23%; 95% CI 11-35) were found to have WMI (four minimal, three moderate, and four severe). In 10 of the 11 newborns, the WMI was associated with restricted diffusion on apparent diffusion coefficient maps. An increasing severity of WMI was associated with lower gestational age at birth (p = 0.05), but not lower birth weight. Newborns with WMI had milder encephalopathy and fewer clinical seizures relative to other newborns in the cohort. Other brain injuries were seen in three of the 11 newborns: basal nuclei predominant pattern of injury in one and cortical strokes in two. These findings suggest that WMI in the term newborn is acquired near birth and that the state of brain maturation is an important determinant of this pattern of brain injury.

Genetic epileptic encephalopathies: is all written into the DNA?

PubMed

Striano, Pasquale; de Jonghe, Peter; Zara, Federico

2013-11-01

Epileptic encephalopathy is a condition in which epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control. However, experimental evidence supporting this clinical observation are still poor and the causal relationship between pharmacoresistant seizures and cognitive outcome is controversial. In the past two decades, genetic studies shed new light onto complex mechanisms underlying different severe epileptic conditions associated with intellectual disability and behavioral abnormalities, thereby providing important clues on the relationship between seizures and cognitive outcome. Dravet syndrome is a childhood disorder associated with loss-of-function mutations in SCN1A and is characterized by frequent seizures and severe cognitive impairment, thus well illustrating the concept of epileptic encephalopathy. However, it is difficult to determine the causative role of the underlying sodium channel dysfunction and that of the consequent seizures in influencing cognitive outcome in these children. It is also difficult to demonstrate whether a recognizable profile of cognitive impairment or a definite behavioral phenotype exists. Data from the laboratory and the clinics may provide greater insight into the degree to which epileptic activity may contribute to cognitive impairment in individual syndromes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-type bovine spongiform encephalopathy

USDA-ARS?s Scientific Manuscript database

Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from normal cellular prion protein to pathogenic misfolded conformation. This conversion has been used for in vitro assays including serial protein misfolding amplification...

Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy.

PubMed

Kimer, N; Krag, A; Møller, S; Bendtsen, F; Gluud, L L

2014-07-01

Rifaximin is recommended for prevention of hepatic encephalopathy (HE). The effects of rifaximin on overt and minimal HE are debated. To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) on rifaximin for HE. We performed electronic and manual searches, gathered information from the U.S. Food and Drug Administration Home Page, and obtained unpublished information on trial design and outcome measures from authors and pharmaceutical companies. Meta-analyses were performed and results presented as risk ratios (RR) with 95% confidence intervals (CI) and the number needed to treat. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate the risk of bias and sources of heterogeneity. We included 19 RCTs with 1370 patients. Outcomes were recalculated based on unpublished information of 11 trials. Overall, rifaximin had a beneficial effect on secondary prevention of HE (RR: 1.32; 95% CI 1.06-1.65), but not in a sensitivity analysis on rifaximin after TIPSS (RR: 1.27; 95% CI 1.00-1.53). Rifaximin increased the proportion of patients who recovered from HE (RR: 0.59; 95% CI: 0.46-0.76) and reduced mortality (RR: 0.68, 95% CI 0.48-0.97). The results were robust to adjustments for bias control. No small study effects were identified. The sequential analyses only confirmed the results of the analysis on HE recovery. Rifaximin has a beneficial effect on hepatic encephalopathy and may reduce mortality. The combined evidence suggests that rifaximin may be considered in the evidence-based management of hepatic encephalopathy. © 2014 John Wiley & Sons Ltd.

GNAO1 encephalopathy: Broadening the phenotype and evaluating treatment and outcome.

PubMed

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; Guerrini, Renzo

2017-04-01

To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1 -related disease. 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. 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. 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.

Effects of probiotic therapy on hepatic encephalopathy in patients with liver cirrhosis: an updated meta-analysis of six randomized controlled trials.

PubMed

Xu, Jun; Ma, Rui; Chen, Li-Feng; Zhao, Li-Jun; Chen, Kan; Zhang, Ren-Bing

2014-08-01

Liver cirrhotic patients with hepatic encephalopathy have poor prognosis. Probiotics alter the intestinal microbiota and reduce the production of ammonia. We conducted a meta-analysis about the role of probiotics on liver cirrhotic patients with hepatic encephalopathy. We collected the relevant literatures up to February 21, 2014 from databases of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. A statistical analysis was conducted by RevMan 5.2 and STATA 12.0 software. Six randomized controlled trials involving 496 liver cirrhotic patients were included. The results showed that probiotic therapy significantly reduced the development of overt hepatic encephalopathy (OR [95% CI]: 0.42 [0.26, 0.70], P=0.0007). However, probiotics did not affect mortality, levels of serum ammonia and constipation (mortality: OR [95% CI]: 0.73 [0.38, 1.41], P=0.35; serum ammonia: WMD [95% CI]: -3.67 [-15.71, 8.37], P=0.55; constipation: OR [95% CI]: 0.67 [0.29, 1.56], P=0.35). Probiotics decrease overt hepatic encephalopathy in patients with liver cirrhosis.

Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle.

PubMed

Okada, Hiroyuki; Iwamaru, Yoshifumi; Imamura, Morikazu; Miyazawa, Kohtaro; Matsuura, Yuichi; Masujin, Kentaro; Murayama, Yuichi; Yokoyama, Takashi

2017-02-01

To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle.

Epileptic Encephalopathies and Their Relationship to Developmental Disorders: Do Spikes Cause Autism?

ERIC Educational Resources Information Center

Tharp, Barry R.

2004-01-01

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10-15% of children with pervasive developmental disorders (PDD) and 8-10% have epileptiform EEG abnormalities without…

[The bioelectric activity of the brain in dyscirculatory encephalopathy and arterial hypertension developed in the Chernobyl nuclear disaster liquidators].

PubMed

Podsonnaia, I V; Efremushkin, G G; Zhelobetskaia, E D

2012-01-01

The long-term effects of the ionizing radiation on the bioelectric brain activity in the Chernobyl nuclear disaster liquidators with discirculatory encephalopathy and arterial hypertension were studied. We examined 195 male patients, aged from 30 to 65 years, with the clinical presentations of discirculatory encephalopathy, using electroencephalography: 105 patients were liquidators of the Chernobyl nuclear disaster (the main group) and 90 patients had no radiation anamnesis (the comparison group). It has been found that the development of discirculatory encephalopathy in liquidators of the Chernobyl nuclear disaster is mainly associated with the dysfunction of diencephalic and cortical structures. The specificity of the neurofunctional brain abnormalities in liquidators with discirculatory encephalopathy is characterized by the predominance of the low-amplitude and low-frequency alpha-activity or by the lack of alpha-rhythm and by its substitution for the high-frequency beta-rhythm with the presence of theta- and delta-activity and by the more significant flatness of the alpha-rhythm zonation. The presence of the radiation factor in the past history is correlated with the failure of the bioelectric brain activity in the alpha band (r=0.42) that increases risk of abnormal changes by a factor of 10 (p<0.001). The liquidators with arterial hypertension are characterized by the more frequent occurrence of the asymmetry of the recorded bioelectric potentials between the similar hemispheric areas, by the more significant difference in the external stimulus response of the brain (functional tests). The results indicate the more complicated and diffuse lesion of the brain in the liquidators of the Chernobyl nuclear disaster in the post-radiation period during the development of discirculatory encephalopathy and arterial hypertension.

Endovascular Management of Refractory Hepatic Encephalopathy Complication of Transjugular Intrahepatic Portosystemic Shunt (TIPS): Comprehensive Review and Clinical Practice Algorithm

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

Pereira, Keith, E-mail: keithjppereira@gmail.com; Carrion, Andres F., E-mail: andres.carrionmonsa@jhsmiami.org; Salsamendi, Jason, E-mail: JSalsamendi@med.miami.edu

Transjugular intrahepatic portosystemic shunt (TIPS) has evolved as an effective intervention for treatment of complications of portal hypertension. The use of polytetrafluoroethylene-covered stents have improved the patency of the shunts and diminished the incidence of TIPS dysfunction. However, TIPS-related refractory hepatic encephalopathy (rHE) poses a significant challenge. Approximately 3–7 % of patients with TIPS develop rHE. Refractory hepatic encephalopathy is defined as a recurrent or persistent encephalopathy despite appropriate medical treatment. Hepatic encephalopathy can be an extremely debilitating complication that profoundly affects quality of life. The approach to management of patients with rHE is complex and typically requires collaboration between differentmore » specialties. Liver transplantation is the ultimate treatment for rHE; however, the ongoing shortage of organ donation markedly limits this treatment option. Alternative therapies such as shunt occlusion or reduction can control symptoms and serve as a ‘bridge’ therapy to liver transplantation. Therefore, interventional radiologists play a key role in the management of these patients by offering a variety of endovascular techniques. The purpose of this review is to highlight some of these endovascular techniques and to develop a therapeutic algorithm that can be applied in clinical practice for the management of rHE.« less

A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome with Intracardiac Thrombus [corrected].

PubMed

Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong; Cho, Wook Hyun

2013-03-01

Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.

Quantitative analysis of brain magnetic resonance imaging for hepatic encephalopathy

NASA Astrophysics Data System (ADS)

Syh, Hon-Wei; Chu, Wei-Kom; Ong, Chin-Sing

1992-06-01

High intensity lesions around ventricles have recently been observed in T1-weighted brain magnetic resonance images for patients suffering hepatic encephalopathy. The exact etiology that causes magnetic resonance imaging (MRI) gray scale changes has not been totally understood. The objective of our study was to investigate, through quantitative means, (1) the amount of changes to brain white matter due to the disease process, and (2) the extent and distribution of these high intensity lesions, since it is believed that the abnormality may not be entirely limited to the white matter only. Eleven patients with proven haptic encephalopathy and three normal persons without any evidence of liver abnormality constituted our current data base. Trans-axial, sagittal, and coronal brain MRI were obtained on a 1.5 Tesla scanner. All processing was carried out on a microcomputer-based image analysis system in an off-line manner. Histograms were decomposed into regular brain tissues and lesions. Gray scale ranges coded as lesion were then brought back to original images to identify distribution of abnormality. Our results indicated the disease process involved pallidus, mesencephalon, and subthalamic regions.

Functional neuroimaging in epileptic encephalopathies.

PubMed

Siniatchkin, Michael; Capovilla, Giuseppe

2013-11-01

Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive disability in EEs remain unclear. This review summarized neuroimaging studies that have tried to describe specific fingerprints of brain activation in EE. Although the epileptic activity can be generated individually in different brain regions, it seems likely that the activity propagates in a syndrome-specific way. In some EEs, the epileptiform discharges were associated with an interruption of activity in the default mode network. In another EE, other mechanisms seem to underlie cognitive disability associated with epileptic activity, for example, abnormal connectivity pattern or interfering activity in the thalamocortical network. Further neuroimaging studies are needed to investigate the short-term and long-term impact of epileptic activity on cognition and development. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Neuroimaging features in subacute encephalopathy with seizures in alcoholics (SESA syndrome)

PubMed Central

Drake-Pérez, Marta; de Lucas, Enrique Marco; Lyo, John; Fernández-Torre, José L.

2017-01-01

Purpose To describe the neuroimaging findings in subacute encephalopathy with seizures in alcoholics (SESA syndrome). Methods 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. Results 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%. Conclusions 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. PMID:27391464

Clinical and videofluoroscopic diagnosis of dysphagia in chronic encephalopathy of childhood*

PubMed Central

Araújo, Brenda Carla Lima; Motta, Maria Eugênia Almeida; de Castro, Adriana Guerra; de Araújo, Claudia Marina Tavares

2014-01-01

Objective To evaluate the contribution of deglutition videofluoroscopy in the clinical diagnosis of dysphagia in chronic encephalopathy of childhood. Materials and Methods The study sample consisted of 93 children diagnosed with chronic encephalopathy, in the age range between two and five years, selected by convenience among patients referred to the authors' institution by speech therapists, neurologists and gastroenterologists in the period from March 2010 to September 2011. The data collection was made at two different moments, by different investigators who were blind to each other. Results The method presented low sensitivity for detecting aspiration with puree consistency (p = 0.04). Specificity and negative predictive value were high for clinical diagnosis of dysphagia with puree consistency. Conclusion In the present study, the value for sensitivity in the clinical diagnosis of dysphagia demonstrates that this diagnostic procedure may not detect any change in the swallowing process regardless of the food consistency used during the investigation. Thus, the addition of the videofluoroscopic method can significantly contribute to the diagnosis of dysphagia. PMID:25741054

Advances in magnetic resonance neuroimaging techniques in the evaluation of neonatal encephalopathy.

PubMed

Panigrahy, Ashok; Blüml, Stefan

2007-02-01

Magnetic resonance (MR) imaging has become an essential tool in the evaluation of neonatal encephalopathy. Magnetic resonance-compatible neonatal incubators allow sick neonates to be transported to the MR scanner, and neonatal head coils can improve signal-to-noise ratio, critical for advanced MR imaging techniques. Refinement of conventional imaging techniques include the use of PROPELLER techniques for motion correction. Magnetic resonance spectroscopic imaging and diffusion tensor imaging provide quantitative assessment of both brain development and brain injury in the newborn with respect to metabolite abnormalities and hypoxic-ischemic injury. Knowledge of normal developmental changes in MR spectroscopy metabolite concentration and diffusion tensor metrics is essential to interpret pathological cases. Perfusion MR and functional MR can provide additional physiological information. Both MR spectroscopy and diffusion tensor imaging can provide additional information in the differential of neonatal encephalopathy, including perinatal white matter injury, hypoxic-ischemic brain injury, metabolic disease, infection, and birth injury.