Onset Of Encephalopathy Research Articles

Novel homozygous ESAM variants in two families with perinatal strokes showing variable neuroradiologic and clinical findings.

Biallelic loss of function variants in ESAM (endothelial cell adhesion molecule) have recently been reported in 14 individuals (9 families) presenting with prenatal intracranial hemorrhage. Here, we describe four patients from two unrelated families in whom three of them presented with variable onset encephalopathy and seizures while one only displayed profound delay without seizures. Brain MRI showed variable onset intracranial hemorrhage that evolved to hydrocephalus in 3 patients, whereas hemosiderin deposits, white matter volume loss, and porencephalic cysts were noted in one patient. Unlike the majority of described cases, the youngest brother of the first family did not show microcephaly and failure to thrive. Exome sequencing identified two novel homozygous ESAM variants. A splice variant (c.731-2A>G) was identified in one family which was confirmed by investigating the patient's mRNA to result in exon skipping and early protein truncation. In addition, a missense variant (c.561G>C; p.Trp187Cys) was identified in the other family, which is the first disease causing missense variant to be described in patients with ESAM deficient phenotype. In addition, a maternally inherited pathogenic MC4R variant (c.811T>C; p.Cys271 Arg) was also identified in the youngest brother of the first family. Variants in the MC4R gene are associated with a non-syndromic form of obesity that could explain the unusual macrocephaly and obesity. Our work establishes ESAM as a tight junction gene that can present with variable neuroradiological and clinical phenotypes when mutated. Moreover, it refines the phenotype of this ultrarare syndrome and extends the number and type of variants described to date.

Disproportionality analysis of amenamevir-induced encephalopathy using the Japanese adverse drug event report database

IntroductionAnti-herpesvirus drug-induced encephalopathy can complicate herpes zoster treatment; however, the association between the recently developed anti-herpesvirus drug amenamevir and encephalopathy development remains unknown. Determining the characteristics of amenamevir-induced encephalopathy is essential for potentially improving patient outcomes in the treatment of herpes zoster. The aim of this study is to identify the association between amenamevir treatment and encephalopathy and to determine the risk factors for amenamevir-induced encephalopathy via disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. MethodWe conducted a retrospective observational study using anonymized data from the JADER database. Encephalopathy was defined according to the Standardized Medical Dictionary for Regulatory Activities Queries specific to “Noninfectious encephalopathy/delirium.” Disproportionality analysis was used to calculate the reporting odds ratios (RORs) and 95 % confidence intervals (CIs) to assess associations between amenamevir and encephalopathy. Multivariable logistic regression considered age, gender, chronic kidney disease, and cytochrome P450 3A inhibitor use as potential risk factors. ResultsOut of 713,316 patients, 246 were prescribed amenamevir. The median onset of encephalopathy in these patients was 3 days. Disproportionality of encephalopathy was observed in patients treated with amenamevir (ROR, 3.44; 95 % CI, 2.48–4.78). Furthermore, multivariable logistic regression analysis suggested that an age of ≥70 years was associated with amenamevir-induced encephalopathy (ROR, 7.63; 95 % CI, 2.25–25.9). ConclusionThese results suggest that amenamevir treatment may be associated with encephalopathy, particularly in patients aged ≥70 years. Healthcare providers should be aware of this potential risk, especially in elderly patients, to prevent severe central nervous system complications.

Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy

Influenza-associated encephalopathy (IAE) is extremely acute in onset, with high lethality and morbidity within a few days, while the direct pathogenesis by influenza virus in this acute phase in the brain is largely unknown. Here we show that influenza virus enters into the cerebral endothelium and thereby induces IAE. Three-weeks-old young mice were inoculated with influenza A virus (IAV). Physical and neurological scores were recorded and temporal-spatial analyses of histopathology and viral studies were performed up to 72 h post inoculation. Histopathological examinations were also performed using IAE human autopsy brains. Viral infection, proliferation and pathogenesis were analyzed in cell lines of endothelium and astrocyte. The effects of anti-influenza viral drugs were tested in the cell lines and animal models. Upon intravenous inoculation of IAV in mice, the mice developed encephalopathy with brain edema and pathological lesions represented by micro bleeding and injured astrocytic process (clasmatodendrosis) within 72 h. Histologically, massive deposits of viral nucleoprotein were observed as early as 24 h post infection in the brain endothelial cells of mouse models and the IAE patients. IAV inoculated endothelial cell lines showed deposition of viral proteins and provoked cell death, while IAV scarcely amplified. Inhibition of viral transcription and translation suppressed the endothelial cell death and the lethality of mouse models. These data suggest that the onset of encephalopathy should be induced by cerebral endothelial infection with IAV. Thus, IAV entry into the endothelium, and transcription and/or translation of viral RNA, but not viral proliferation, should be the key pathogenesis of IAE.

Identification of novel mutations in TPK1 and SLC19A3 genes in families exhibiting thiamine metabolism dysfunction syndrome

Background and aimsThe occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders. Material and methodsThe selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative. ResultsThe first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the SLC19A3 gene. ConclusionsCollectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.

Long-term effectiveness and tolerability of ketogenic diet therapy in patients with genetic developmental and epileptic encephalopathy onset within the first 6 months of life.

To investigate the effectiveness and tolerability of ketogenic diet therapy (KDT) in patients with developmental and epileptic encephalopathy (DEE) associated with genetic etiology which onset within the first 6 months of life, and to explore the association between response to KDT and genotype/clinical parameters. We retrospectively reviewed data from patients with genetic DEE who started KDT at Beijing Children's Hospital between January 1, 2016, and December 31, 2021. A total of 32 patients were included, involving 14 pathogenic or likely pathogenic single genes, and 16 (50.0%) patients had sodium/potassium channel gene variants. The median age at onset of epilepsy was 1.0 (IQR: 0.1, 3.0) months. The median age at initiation of KDT was 10.0 (IQR: 5.3, 13.8) months and the median duration of maintenance was 14.0 (IQR: 7.0, 26.5) months, with a mean blood β-hydroxybutyrate of 2.49 ± 0.62 mmol/L. During the maintenance period of KDT, 26 (81.3%) patients had a ≥50% reduction of seizure frequency, of which 12 (37.5%) patients achieved seizure freedom. Better responses were observed in patients with STXBP1 variants, with four out of five patients achieving seizure freedom. There were no statistically differences in the age of onset, duration of epilepsy before KDT, blood ketone values, or the presence of ion channel gene variants between the seizure-free patients and the others. The most common adverse effects were gastrointestinal side effects, which occurred in 21 patients (65.6%), but all were mild and easily corrected. Only one patient discontinued KDT due to nephrolithiasis. KDT is effective in treating early onset genetic DEE, and no statistically significant relationship has been found between genotype and effectiveness in this study. KDT is well tolerated in most young patients, with mild and reversible gastrointestinal side effects being the most common, but usually not the reason to discontinue KDT. This study evaluated the response and side effects of ketogenic diet therapy (KDT) in patients who had seizures within the first 6 months of life, and were diagnosed with genetic developmental and epileptic encephalopathy (DEE), a type of severe epilepsy with developmental delay caused by gene variants. Thirty-two patients involving 14 gene variants who started KDT at Beijing Children's Hospital between were included. KDT was effective in treating early onset genetic DEE in this cohort, and patients with STXBP1 variants responded better; however, no statistically significant relationship was found between gene variant and response. Most young patients tolerated KDT well, with mild and reversible gastrointestinal side effects being the most common.

Characteristics of Visual Cognition in Patients with Anoxic Encephalopathy: An Eye-tracking Study.

: Despite the frequent occurrence of visual cognitive impairment after anoxic encephalopathy, only a few studies have analyzed gaze movements following encephalopathy. This study determined the visual cognitive characteristics of patients with anoxic encephalopathy using an eye-tracking system. : This study included ten patients with anoxic encephalopathy and ten age/sex-matched controls. Factors for anoxic encephalopathy onset and brain imaging findings were extracted from medical records. An eye-tracking system was used to track eye movements during three visual search tasks (pop-out, serial search, and saliency) in patient and healthy control groups. The average target search time, number of saccades, and number of fixations to salient stimuli were compared. : Stagnant blood flow, observed in six of ten patients, was the most common cause of disease onset, four of whom exhibited hypoperfusion in bilateral occipital or parietal lobes on single-photon emission computed tomography. The patient group required longer search times during all visual search tasks and a higher number of saccades during pop-out and serial search tasks. However, no significant difference was observed between the two groups for the number of fixations to salient stimuli during the saliency task. : Following anoxic encephalopathy, bottom-up (pop-out task) and top-down (serial search task) gaze control were considered impaired because of extensive parieto-occipital lobe damage after blood flow stagnation. Patients exhibited reduced top-down function for finding targets (serial search task) but relatively retain inhibitory function for salient stimuli (saliency task). Gaze analysis can be used to reveal the clinical characteristics of anoxic encephalopathy.

Myelin oligodendrocyte glycoprotein (MOG) antibody positive disease presenting as acute disseminated encephalomyelitis and unilateral optic neuritis

The autoantibody against myelin oligodendrocyte glycoprotein (MOG-abs) is a recognized biomarker in acquired demyelinating syndromes. The diversity in clinical and neuroimaging phenotypes is still being understood in the paediatric population. The presenting clinical phenotype strongly depends on the age at onset. Acute disseminated encephalomyelitis (ADEM) and ADEM-like phenotypes are common in younger children, but optic neuritis (ON), often bilateral, is predominantly seen in females and older children and or adults.We present a 6.5-year-old boy with a rapid onset encephalopathy due to ADEM and a unilateral longitudinally affected optic neuritis detected on neuroimaging. His serum was positive for MOG-abs but negative for Aquaporin-4 antibodies. His cerebrospinal fluid was negative for oligoclonal bands. He gradually improved following treatment with intravenous high-dose methylprednisolone and five cycles of plasma exchange. Complete clinical recovery was achieved within twelve weeks of admission.Conclusion: Contrary to the usual older age of MOG-ON, and the bilateral involvement, this case illustrates a unilateral ON in a six-year-old boy occurring in conjunction with a MOG-ab positive encephalomyelitis.

Characteristics and predictors of disease course in children initially presenting with ADEM

ADEM is an inflammatory disease, with new onset polyfocal neurologic symptoms, encephalopathy and multifocal demyelination, typically in childhood. Initial diagnosis of ADEM is challenging and up to 20 % of children with MS or NMOSD are initially diagnosed with ADEM.We describe characteristics of patients with monophasic ADEM vs. recurrent demyelinating syndromes at onset and identify features consistent with monophasic course.This is a multicenter observational study of children with demyelinating disease, followed at 12 regional pediatric MS centers. Descriptive statistics were used to report patient characteristics, clinical/imaging features and outcomes. Logistic regression was used to predict features associated with monophasic course.As of July 2019, 837 children with final diagnosis of ADEM (n = 79), MS (n = 646) or NMOSD (n = 112) were identified. The mean follow-up was 5·7 +/- 3·2 years. ADEM patients were youngest with mean age at first event 5·2 +/- 3·8 years (p < 0.001) and male predominant (66 %) (p < 0·001). After 2 years of follow-up, 83 % of patients initially diagnosed with monophasic ADEM retained this diagnosis. In multivariable analysis, older age (OR 1·16 [95 % CI 1·02 – 1·33] for 1-year increase, p = 0·02), presenting with optic neuritis (OR 8.18 [95 % CI 1.88 – 35.64], p = 0·005) and presence of gadolinium enhancement (OR 4.08 [95 % CI 1.38 – 12.08], p = 0·011) were associated with reclassification of ADEM to MS, NMOSD or DDNOS within 2 years.Children with monophasic ADEM vs. those reclassified as other demyelinating disorders are younger at onset, and less likely to have optic neuritis or gadolinium-enhancing lesions at onset.

Steroid responsive encephalopathy associated with autoimmune thyroiditis as a cause of acuteencephalopathy.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), known as Hashimoto's encephalopathy (HE), represents a heterogeneous group of neurological and neuropsychiatric symptoms associated with a presence of antithyroid antibodies in case of other causes of encephalopathy were excluded. Clinical symptoms most commonly includes acute onset of encephalopathy, behaviour changes and cognitive dysfunction, epileptic seizures as well as cerebellar and extrapyramidal symptoms. Corticoids provides rapid and sustained therapeutic benefit in most patients and only a few patients require other immunosuppressive therapy such as plasmapheresis, intravenous immunoglobulins, or others. We present the cases of two patients with acute onset of encephalopathy, status epilepticus based on SREAT, with rapid improvement after steroid treatment.

Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity.

Genetic variants associated with developmental and epileptic encephalopathies have been identified in the GABRB3 gene that encodes the β3 subunit of GABAA receptors. Typically, variants alter receptor sensitivity to GABA resulting in either gain- or loss-of-function, which correlates with patient phenotypes. However, it is unclear how another important receptor property, desensitization, contributes to the greater clinical severity of gain-of-function variants. Desensitization properties of 20 gain-of-function GABRB3 variant receptors were evaluated using two-electrode voltage-clamp electrophysiology. The parameters measured included current decay rates and steady-state currents. Selected variants with increased or reduced desensitization were also evaluated using whole-cell electrophysiology in transfected mammalian cell lines. Of the 20 gain-of-function variants assessed, 13 were found to alter receptor desensitization properties. Seven variants reduced desensitization at equilibrium, which acts to worsen gain-of-function traits. Six variants accelerated current decay kinetics, which limits gain-of-function traits. All affected patients displayed severe clinical phenotypes with intellectual disability and difficult-to-treat epilepsy. Nevertheless, variants that reduced desensitization at equilibrium were associated with more severe clinical outcomes. This included younger age of first seizure onset (median 0.5 months), movement disorders (dystonia and dyskinesia), epilepsy of infancy with migrating focal seizures (EIMFS) and risk of early mortality. Variants that accelerated current decay kinetics were associated with slightly milder phenotypes with later seizure onset (median 4 months), unclassifiable developmental and epileptic encephalopathies or Lennox-Gastaut syndrome and no movement disorders. Our study reveals that gain-of-function GABRB3 variants can increase or decrease receptor desensitization properties and that there is a correlation with the degree of disease severity. Variants that reduced the desensitization at equilibrium were clustered in the transmembrane regions that constitute the channel pore and correlated with greater disease severity, while variants that accelerated current decay were clustered in the coupling loops responsible for receptor activation and correlated with lesser severity.

A STUDY OF THIAMINE DEFICIENCY IN PATIENTS WITH ACUTE ONSETENCEPHALOPATHY

Introduction:Vitamin B1, also known as thiamine, and its crucial role in energy metabolism and proper functioning of the nervous and cardiovascular systems. Thiamine is an essential vitamin that must be obtained through diet since the body does not produce it naturally. It is stored in the liver but only lasts for about 18 days. Thiamine is absorbed in the duodenum and transported across the blood-brain barrier. The recommended daily intake varies based on age, health condition, and life stages.Thiamine plays a vital role in various biochemical pathways in the brain, including energy production, lipid metabolism, neurotransmitter synthesis, and synaptic transmission. Thiamine deficiency can have diverse clinical effects, affecting the nervous and cardiovascular systems most severely and potentially leading to death if left untreated.Different thiamine deficiency syndromes are identified, including dry beriberi (peripheral neurologic manifestations), wet beriberi (cardiac effects), gastrointestinal beriberi (digestive symptoms), and Wernickes encephalopathy (neuropsychiatric condition). While alcohol abuse-associated malnutrition is a common cause of Wernickes encephalopathy in developed countries, it can also occur due to other factors such as decreased thiamine absorption, increased body requirements, or thiamine loss in certain medical conditions.Thiamine deficiency is considered a potential public health concern, particularly in communities in South Asia and West Africa, where diets heavily reliant on polished rice or cassava may contribute to the risk. Studies have shown varying prevalence rates of thiamine deficiency in different populations, including healthy adults and pregnant/lactating mothers in South-East Asia and India. While specific population-based studies are lacking in the Kashmiri population, preliminary evidence suggests the presence of thiamine deficiency disorders in infants, peripartum females, and adults with diverse presentations. Objectives: Early detection and treatment of Patients with Encephalopathy related to Thiamine deficiency Study Design/ Methodology:The study was hospital-based and prospective in nature, conducted in the Department of General Medicine, SMHS, GMC - Srinagar from May 2021 to September 2022. The study was done on patients aged more than 18 years of age attending emergency department of Government Medical College, Srinagar with acute onset encephalopathy. Observations And Results:In this study, 96 patients with acute onset encephalopathy were recruited based on CAM score criteria. The patients were divided into two groups: a low thiamine group and a normal thiamine group, based on their whole-blood thiamine levels. Among the patients, 15.6% had normal thiamine levels, while 84.4% had low thiamine levels. The mean thiamine level in the normal thiamine group was 5.46±4.44 ug/dL, and in the low thiamine group, it was 1.35±0.42 ug/dL (p=0.0001). Patients with normal thiamine levels were excluded from further analysis, leaving a group of 84.4% of patients with thiamine deficiency.Within the thiamine deficiency group, patients were further divided into responders and non-responders based on their response to a thiamine challenge. The responders group comprised 17 patients, including 11 males, 6 females (including 3 pregnant females), with a mean age of 36.25±9.44. Non-responders had a mean age of 61.8±15. Among responders, 70.58% had recurrent vomiting compared to 37.5% in non-responders. Confusion was the most common initial presentation in both groups, followed by lethargy. Behavioural changes were seen in a higher percentage of responders compared to non-responders. Ataxia was more prevalent in the responders group.Various laboratory parameters were analyzed between responders and non-responders. There was no significant difference in mean pH, sodium, potassium, total protein, serum albumin, and blood sugar levels between the two groups. However, lactate levels and the drop in lactate following thiamine therapy were higher in responders. Responders had lower levels of serum urea and serum creatinine compared to non-responders.MRI brain findings suggestive of Wernickes encephalopathy were observed in 53% of responders. Polished rice consumption was common among all patients, with 85% of responders and 62% of non-responders consuming polished rice as their main staple diet. Traditional salt tea intake was also prevalent in both groups. Conclusions: Thiamine deficiency can manifest in various clinical scenarios, including recurrent vomiting, hypoxia, electrolyte imbalances (such as hyponatremia and hypernatremia), and systemic diseases like uremia, hepatic encephalopathy, and septic shock. Pregnant women, who experience increased demand and may have thiamine loss due to vomiting, are also at risk of developing thiamine deficiency.The diagnosis of thiamine deficiency is primarily clinical and is confirmed by the response of neurological signs to high-dose intravenous thiamine treatment. MRI is considered the most valuable paraclinical study for diagnosis. Elevated serum lactate levels and the response of lactate to high-dose parenteral thiamine can serve as surrogate markers for thiamine-responsive encephalopathy. It is crucial to administer high doses of parenteral thiamine immediately to patients suspected of having encephalopathy due to thiamine deficiency to prevent complications associated with Wernicke-Korsakoff syndrome.

Two Cases of Juvenile Myelomonocytic Leukemia and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

BackgroundMyelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. MethodsWe investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. ResultsPatient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. ConclusionWe treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.

Abstract Number ‐ 215: Distinct presentation of RCVS and PRES co‐existence and overlap of their pathophysiology

Introduction Reversible cerebral vasoconstriction syndrome (RCVS), is characterized by reversible segmental and multifocal vasoconstrictionof cerebral arteries leading to infarcts and cytotoxic edema. Posterior reversible encephalopathy syndrome (PRES) is characterized by vasogenic edema predominantly in the parieto‐occipital regions associated with acute onset encephalopathy, seizures, headache, and visual disturbances.Whether PRES and RCVS are independent syndromes and sometimes overlapped or part of a continuum process, these theories are still debated. We report a case of a patient with distinct overlapping of RCVS and PRES. Methods Case Report Results 52‐year‐old woman with past medical Hx of Hypertension, Diabetes, Migraines and cocaine use, initially presented with hypertensive emergency andsubacute headaches with worsening confusion. Initial CT head was negative for bleed but showed evolving subcortical hypodensities in the right parietal and left frontal lobes. CTA head and neck showed multifocal intracranial irregularities of bilateral ACAs and MCAs with paucity of left anterior M2 branch, left V3/V4 steno‐occlusion. This vasculopathy and clinical presentation is very consistent with RCVS.MRI of brain showed multiple acute / subacute punctate infarcts in the left corona radiata, bilateral basal ganglia, right greater than left thalami, right dorsal pons, right mesial temporal lobe, bilateral occipital regions. Vasogenic edema was noted in the bilateral border zone regions, right parietal being most prominent with some contrast enhancement. The MRI showed vasogenic edema and cytotoxic edema with multiple infarcts which is consistent with PRES and RCVS vasculopathy. CSF analysis was negative for pleocytosis and showed mildly elevated protein. The patient was started on Verapamil and Aspirin and Atorvastatin for secondary stroke prevention. With improvement in mental status was discharged to Rehab. Conclusions The pathophysiological mechanisms of PRES and RCVS are still unknown. Theories whether RCVS and PRES are independent syndromes and sometimes overlap or part of spectrum, are still debated. However, some common characteristics make conceivable a common origin linked with impaired cerebral autoregulation, endothelial dysfunction, and BBB breakdown. Increased clinical awareness of their co‐existence may help in quickerdiagnosis and treatment.

A curious case of confusion

A curious case of confusion

New Onset Encephalopathy with Toxic Triphasic Waves

AbstractNew onset encephalopathy can have various causes like stroke, trauma, seizures, infections, demyelination, neoplasms, autoimmune, degenerative, and toxic and metabolic etiologies. Triphasic waves in electroencephalogram (EEG) is usually a clue to an ongoing metabolic process. We report a case of a 69-year-old female with bipolar disorder who presented with altered sensorium for the last 2 days. Her metabolic parameters, imaging, and cerebrospinal fluid findings were normal. Her EEG findings in the clinical setting provided a diagnostic clue to lithium toxicity, even though her serum lithium levels were normal. As her sensorium was progressively worsening, she was given a trial of hemodialysis with which she had significant improvement.

New Onset Encephalopathy Associated with Ivermectin Use

New Onset Encephalopathy Associated with Ivermectin Use

Case report of two affected siblings in a family with thiamine metabolism dysfunction syndrome 5: a rare, but treatable neurodegenerative disease

BackgroundThiamine metabolism dysfunction syndrome 5 (THMD5) is a rare inherited metabolic disorder due to thiamine pyrophosphokinase 1(TPK1) deficiency, caused by mutations in TPK1. The core symptoms of the disease is acute or subacute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by acute infectious illness. However, we report two brothers of THMD5 with compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn), but the prognosis is quite different if thiamine suppled. According to our current knowledge, the missense variant c.224 T > A p.(Ile75Asn) was not published previously.Case presentationHere, we describe two affected siblings in a Chinese family, after an uneventful pregnancy to non-consanguineous and healthy parents. The older brother presented with normal development during the first 6 months of life, but developed regression of developmental milestones after, accompanied with muscle hypotonia, and chronic encephalopathy, and died at 1 year and 6 months old. The younger brother presented with acute onset encephalopathy, ataxia, muscle hypotonia, repeatedly triggered by acute infectious illness. He was compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn) identified by whole exome sequencing. He was diagnosed of THMD5 when he was 11 month. Oral supplementation of thiamine 100 mg/day, the symptoms gradually disappeared. At the age of 2 years and 4 months, he stoped thiamine, his symptoms returned and were once again relieved by oral supplementation of thiamine 100 mg/day.ConclusionsTHMD5 is a rare, but treatable neurodegenerative disease, the clinical phenotype ranges from mild to severe. Massive-dose of thiamine supplementation may ameliorate the course of TPK1 deficiency. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis. Treatment with thiamine while awaiting the outcome of diagnostic tests may be a good choice.

Etiology, pathophysiology and management of reye’s syndrome

Reye’s syndrome is defined as a fatal biphasic disorder that clinically described by preceding viral illness, protracted vomiting from one to two days before the onset of encephalopathy and liver dysfunction. Reye’s syndrome can be characterized as a constellation of delirium, fever, convulsions, vomiting, respiratory collapses, stupor, seizures, or coma typically following an earlier viral illness. Encephalopathy can be frequently progresses rapidly from lethargy to coma within twenty four to forty eight hrs. Both universal mitochondrial injury and triglyceride accumulations are the cornerstone etiology of Reye’s syndrome. Accumulation of high concentration of ammonia leads to encephalopathy and anicteric hepatitis with three times rise in liver enzymes. A frequent pathophysiological mechanism of Reye’s syndrome is induction of the mitochondrial permeability transition. The syndrome is correlated with a high mortality rate and the treatment is symptomatic including intensive care management with correction of metabolic abnormalities especially of hypotension, hypo glycaemia and acidosis, control of convulsions, and monitoring of intracranial hypertension due to cerebral edema. Agents to decrease serum ammonia concentrations are also usually used, the most frequent being are neomycin sulfate or lactulose. Anti-emetic such as ondansetron should be given to inhibit vomiting and potential aspiration.

Is poor outcome predictable in posterior reversible encephalopathy syndrome? A case series

Posterior reversible encephalopathy syndrome (PRES) was first described by Hinchey et al. in 1996, as a distinct clinico-radiological disease with clinically presence of acute onset seizures, encephalopathy, headache and/or visual disturbances together with radiological findings of vasogenic brain edema typically in the parieto-occipital white matter.1,2 The prognosis of PRES is generally benign. However, it can result in poor outcome and even death.3-5 We aimed to analyze the clinical findings of PRES patients followed at our institution and identify the possible unfavorable prognostic factors. We retrospectively reviewed the hospital charts of patients diagnosed with PRES in the last two years.

Inpatient Management of Encephalopathy.

Unexplained encephalopathy is a common occurrence in tertiary care centers and neurologic disorders should be considered after ruling out the infectious, toxic and metabolic etiologies. Neuroimaging combined with a thorough history and examination is often helpful in ruling out stroke and fulminant demyelinating encephalopathies. Autoimmune encephalopathy should be suspected in any patient with unexplained acute or subacute onset encephalopathy or rapidly progressing dementia. Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is the most studied form and Hashimoto encephalitis is the most controversial form of autoimmune encephalopathies. Obtaining a combined serum and Cerebrospinal fluid (CSF) autoantibody testing will increase the diagnostic yield of autoimmune and paraneoplastic encephalitis. When diagnosing NMDA receptor antibodies CSF is always more sensitive than serum and in contrast, voltage-gated potassium channel (VGKC) complex antibodies are more readily detectable in serum than in CSF. Neural-specific antibody tests frequently result after several weeks and treatment should be administered without a significant delay to prevent brain damage. Autoimmune encephalitis is often treatment responsive when immunotherapy (glucocorticoids, intravenous immune globulin, plasma exchange) is used in various combinations. The absence of inflammatory markers and autoantibodies in the serum or CSF may not rule out the possibility of paraneoplastic encephalopathies.