Severe Acute Encephalopathy Research Articles

Rapid exome sequencing for children with severe acute encephalopathy – A case series

Increasingly, next-generation sequencing (NGS) is becoming an invaluable tool in the diagnosis of unexplained acute neurological disorders, such as acute encephalopathy/encephalitis. Here, we describe a brief series of pediatric patients who presented at the pediatric intensive care unit with severe acute encephalopathy, initially suspected as infectious or inflammatory but subsequently diagnosed with a monogenic disorder.Rapid exome sequencing was performed during the initial hospitalization of three unrelated patients, and results were delivered within 7–21 days. All patients were previously healthy, 1.5–3 years old, of Muslim Arab descent, with consanguineous parents. One patient presenting with acute necrotizing encephalopathy (ANEC). Her sister presented with ANEC one year prior.Exome sequencing was diagnostic in all three patients. All were homozygous for pathogenic and likely-pathogenic variants associated with recessive disorders; MOCS2, NDUFS8 and DBR1. Surprisingly, the initial workup was not suggestive of the final diagnosis.This case series demonstrates that the use of rapid exome sequencing is shifting the paradigm of diagnostics even in critical care situations and should be considered early on in children with acute encephalopathy. A timely diagnosis can direct initial treatment as well as inform decisions regarding long-term care.

Obstructive sleep apnea: a major risk factor for COVID-19 encephalopathy?

BackgroundThis study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE).MethodsBetween 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and < 8). We compared patients’ characteristics (clinical, biological, brain MRI, EEG, pulmonary CT). The severity of COVID-19 AE relied on the RASS and CAM scores.ResultsMost COVID-19 AE patients presented with a high mNOSAS, suggesting high risk of OSA (> 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52).DiscussionThese observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae.

Severe Acute Liver Dysfunction Induces Delayed Hepatocyte Swelling and Cytoplasmic Vacuolization, and Delayed Cortical Neuronal Cell Death.

Liver dysfunction is the main cause of hepatic encephalopathy. However, histopathological changes in the brain associated with hepatic encephalopathy remain unclear. Therefore, we investigated pathological changes in the liver and brain using an acute hepatic encephalopathy mouse model. After administering ammonium acetate, a transient increase in the blood ammonia level was observed, which returned to normal levels after 24 h. Consciousness and motor levels also returned to normal. It was revealed that hepatocyte swelling, and cytoplasmic vacuolization progressed over time in the liver tissue. Blood biochemistry also suggested hepatocyte dysfunction. In the brain, histopathological changes, such as perivascular astrocyte swelling, were observed 3 h after ammonium acetate administration. Abnormalities in neuronal organelles, especially mitochondria and rough endoplasmic reticulum, were also observed. Additionally, neuronal cell death was observed 24 h post-ammonia treatment when blood ammonia levels had returned to normal. Activation of reactive microglia and increased expression of inducible nitric oxide synthase (iNOS) were also observed seven days after a transient increase in blood ammonia. These results suggest that delayed neuronal atrophy could be iNOS-mediated cell death due to activation of reactive microglia. The findings also suggest that severe acute hepatic encephalopathy causes continued delayed brain cytotoxicity even after consciousness recovery.

Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2.

To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes. A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge. Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01). Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.

Viral, Bacterial, Metabolic, and Autoimmune Causes of Severe Acute Encephalopathy in Sub-Saharan Africa: A Multicenter Cohort Study

To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa. One hundred thirty-four children (6 months to 18years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical referral centers in Uganda, Malawi, and Rwanda were enrolled between 2015 and 2016. Locally available diagnostic tests could be supplemented in 117 patients by viral, bacterial, and 16s quantitative polymerase chain reaction testing, metagenomics, untargeted metabolomics, and autoimmune immunohistochemistry screening. Fourteen (12%) cases of viral encephalopathies, 8 (7%) cases of bacterial central nervous system (CNS) infections, and 4 (4%) cases of inherited metabolic disorders (IMDs) were newly identified by additional diagnostic testing as the most likely cause of encephalopathy. No confirmed cases of autoimmune encephalitis were found. Patients for whom additional diagnostic testing aided causal evaluation (aOR 3.59, 90% CI 1.57-8.36), patients with a viral CNS infection (aOR 7.91, 90% CI 2.49-30.07), and patients with an IMD (aOR 9.10, 90% CI 1.37-110.45) were at increased risk for poor outcome of disease. Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute encephalopathy in children in Uganda, Malawi, and Rwanda that are missed by conventional diagnostics and are associated with poor outcome of disease. Improved diagnostic capacity may increase diagnostic yield and might improve outcome of disease.

Frequency of Nonconvulsive Seizures among Pediatric Systemic Cancer Patients with Acute Encephalopathy: Emergent Bedside EEG in Resource Constrained Communities

Purpose: To determine the incidence of nonconvulsive seizures (NCSz) among children with systemic cancer, who underwent unexplained acute severe encephalopathy (GCS≤8) during admission in ICUs and Neuro-ICUs.&#x0D; Study Design: Multicenter prospective observational study describing sub-clinical seizures and electroencephalographic (EEG) features of children (1-16 years) with acute unexplained encephalopathy who underwent emergent bedside EEG≥30min monitoring.&#x0D; Material and Methods: We conducted a prospective longitudinal observational study design and EEG assessment of 40 systemic cancer patients age ≤16years, consecutively diagnosed and admitted in intensive care units (ICUs) and neurointensive care units (Neuro-ICUs) of different cancer hospitals with unexplained acute impaired consciousness (GCS≤08) within ≤6hr of such deterioration. Bed-side EEG recordings of ≥30min were done according to the clinical scenario and the requirements of the treating neurologist/intensivist. Patients with brain tumor, brain metastasis, seizures or those with known cause of coma were excluded. Data surrounding clinical, electrographic, and treatment factors were collected Via a prospective systematic review of medical records and EEGs for correlation with diagnosis, change in the diagnosis and management.&#x0D; Results: Over a period of 2 years, 40 children, 22.5% 1-5yeras, 37.5% 6-10years, 40% 11-16years; boys 65% and girls 35%, who had systemic cancer with a median age of 9.8 years with unexplained acute deterioration of conscious level (GCS≤08). This cohort underwent bed-side EEG of ≥30 min, which was abnormal in 100% of the records. The main reasons for EEG requests were: 1) unexplained impaired consciousness 22(55%) and 2) reason one plus subtle convulsion 18(45%). The most common EEG abnormalities were invariant mixed theta-delta slowing (27.5%), followed by Low-amplitude delta pattern plus epileptiform discharges (20%) and there was electrographic evidence of EEG seizures in 17(42.5%) of the cohort. These electrographic seizures were present in 55.5% of 18 patients with subtle convulsions, whereas were documented only in 20% of the 22 patients without such movements. Electrographic seizures among patients with subtle convulsions responded to antiseizure drugs in 75% cases as compared 50% such response among patients without such convulsions.&#x0D; Conclusion: Emergent bed-side EEG record of ≥30 min is useful in systemic cancer patients admitted in NCUs and Neuro-ICUs with acutely impaired consciousness with or without abnormal body movements. Neurology consultation and EEG studies in these comatose patients provide useful diagnostic information.

Severe Acute Hepatic Dysfunction Induced by Ammonium Acetate Treatment Results in Choroid Plexus Swelling and Ventricle Enlargement in the Brain.

Hepatic encephalopathy is a major cause of liver failure. However, the pathophysiological role of ventricle enlargement in brain edema remains unclear. Here, we used an acute hepatic encephalopathy mouse model to examine the sequential pathological changes in the brain associated with this condition. We collected tissue samples from experimental animals treated with ammonium acetate at 3 and 24 h post-injection. Despite the normalization of the animal’s ammonia levels, samples taken at 24 h after injection exhibited distinct enlargement of lateral ventricles. The choroid plexus samples obtained at 3 h post-ammonium acetate treatment indicated enlargement; however, this swelling was reduced at the later timepoint. The aquaporin-1 proteins that regulate the choroid plexus were localized both in the apical membrane and the cytoplasm of the epithelia in the control; however, they translocated to the apical membranes of the epithelia in response to ammonia treatment. Therefore, severe acute hepatic encephalopathy induced by ammonium acetate administration caused enlargement of the ventricles, through swelling of the choroid plexus and aquaporin-1 transport and aggregation within the apical membranes.

Impact of direct acting antivirals (DAA) on neurologic disorders in chronic hepatitis C.

Neurologic and neuropsychiatric manifestations sometimes provide the first evidence of an unknown HCV infection. These conditions develop with a variable ranging of morbidity, including: "brain fog," fatigue, subtle cognitive and attention impairment, but also with more severe complications or acute presentation, like encephalomyelitis, encephalopathy, stroke and peripheral nerves involvement. We performed a systematic literature search on PubMed, Cochrane Library and Web of Science databases for articles only in English language, that assessed the relationship between "DAA treatment and neurologic disorders" and after the attainment of SVR in full reports of cases that received the DAA schedule from January 2015 to December 2019. The following terms were used: "chronic Hepatitis C," "HCV," "DAA," "direct-acting antiviral," "SVR," "sustained virologic response," peripheral neuropathy" and "neurologic diseases or disorders." HCV infection does not only involve the liver, causing cirrhosis and hepatocellular carcinoma (HCC), but also induces extrahepatic manifestations (EHM), mainly due to a complex immune disease, that damage small and medium vessels, called "mixed cryoglobulinemic vasculitis" (MCV). This kind of mechanism generates most of the HCV-induced neurological damages. Since 2015, the availability of direct-acting antiviral (DAA) oral molecules interfering with HCV replication has completely revolutionized therapeutic options and the target population, which now includes patients aged 12 to 80 years and with advanced liver disease. Relevant was the highlighted DAA effectiveness by achievement of a sustained virologic response (SVR) in about 95% of cases, showing a great tolerability. This favorable effect has arisen in a wide category of patients infected by HCV, including subjects with cirrhosis and complications and/or with EHM, who showed a significant improvement of their symptoms and the disease regression. In this concise review, we examine the clinical outcomes after the introduction of the DAA for the treatment of chronic hepatitis C (CHC), focusing on the neurologic disorders and concluding that there is a strong amelioration of neurologic conditions in several cases, particularly, after attaining the viral eradication with a favorable course in most treated cases.

Brain MR patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients.

Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n=24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.

Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations

BackgroundATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. AimWe aimed to describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. MethodsA retrospective chart review of a cohort of seven patients was conducted. Response to open-label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. ResultsPatients (age 2.5–20 years) had symptom onset at an early age (6 days–1 year). Seizures were either focal or generalized. Common features were: drug resistance, recurrent status epilepticus, etc., severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks–4.8 years) with some improvements reported in all five. ConclusionsOur observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure–function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.

SUN-511 Thyroid Storm Caused by Subacute Thyroiditis in a Patient with Methicillin-Resistant Staphylococcus Aureus Septicemia

Introduction:Thyroid storm is a rare disorder with high mortality risk. It is often precipitated by an acute event in a patient with longstanding untreated hyperthyroidism. However, thyroid storm is rarely reported as a result of subacute thyroiditis (SAT). To the best of our knowledge, there are only three documented cases of thyroid storm caused by SAT. Herein we report the first patient with thyroid storm caused by SAT associated with methicillin-resistant Staphylococcus aureus (MRSA) septicemia and intravenous drug abuse (IVDA).Case:A 19-year old Caucasian woman with a history of IVDA presented with right upper extremity abscess. Symptoms included confusion, agitation, fever, chills, generalized pain, malaise, nausea, and vomiting. Heart rate was over 140, and she was found to have fever and leukocytosis. She was admitted with severe sepsis and acute encephalopathy. On exam, she had a diffusely enlarged and exquisitely tender thyroid gland without discrete nodules or bruit. Thyroid tests were consistent with primary thyrotoxicosis (TSH 0.026 IU/mL, free T3 16.90 pg/mL, and free T4 > 6.99 ng/dL). Burch-Wartofsky score was 75, highly suggestive of thyroid storm. In addition to treating her sepsis, the patient was started on a beta blocker, high dose hydrocortisone, and methimazole. Thyroid ultrasound showed a diffusely enlarged heterogeneous thyroid gland with decreased flow on color Doppler. Upon improvement, the patient admitted to symptoms of anterior neck pain, heat intolerance, palpitations, excessive sweating, and anxiety for two days prior to presentation. Blood cultures later grew MRSA. Methimazole was discontinued when the thyrotropin-receptor antibody result came back negative. The patient continued to improve clinically. Her thyroid tenderness improved, and her free T4 and T3 decreased over a 3-week period. Steroids were tapered off.Discussion:SAT usually causes mild to moderate thyrotoxicosis. It is unusual for SAT to cause thyroid storm. Identifying such a diagnosis in a patient with sepsis is complex. In a septic patient, it is crucial to obtain detailed history, perform a comprehensive physical exam (including neck exam), and have a high level of clinical suspicion for thyroid storm in order to reach the diagnosis early and institute appropriate interventions. Establishing the underlying etiology of the thyrotoxicosis would have long term implications regarding prognosis and treatment.

Gardnerella vaginalis bacteremia associated with severe acute encephalopathy in a young female patient

Gardnerella vaginalis is a facultative anaerobic bacterium that inhabits the genitourinary tract of both healthy women and those with bacterial vaginosis. We report a case of G. vaginalis bacteremia associated with severe toxic encephalopathy in a young woman. Anaerobic blood cultures yielded pure growth of small gram-variable rods later identified as G. vaginalis by both rapid biochemical tests and 16S rRNA gene sequencing. The patient recovered after treatment with amoxicillin-clavulanate according to the in vitro susceptibility testing. The complete genome of G. vaginalis isolate from blood cultures was determined. In vitro G. vaginalis isolate produced elevated amounts of a pore-forming toxin vaginolysin compared to control G. vaginalis isolates. We hypothesize that this toxin, if produced in high amounts in blood, is able to disrupt the blood-brain barrier and exert a toxic activity on brain cells.

Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants

To evaluate the ability of the bilirubin-induced neurologic dysfunction (BIND) score to predict residual neurologic and auditory disability and to document the relationship of BIND score to total serum bilirubin (TSB) concentration. The BIND score (assessing mental status, muscle tone, and cry patterns) was obtained serially at 6- to 8-hour intervals in 220 near-term and full-term infants with severe hyperbilirubinemia. Neurologic and/or auditory outcomes at 3-5 months of age were correlated with the highest calculated BIND score. The BIND score was also correlated with TSB. Follow-up neurologic and auditory examinations were performed for 145/202 (72%) surviving infants. All infants with severe acute bilirubin encephalopathy (BIND scores 7-9) either died or suffered residual neurologic and auditory impairment. Of 24 cases with moderate encephalopathy (BIND 4-6), 15 (62.5%) resolved following aggressive intervention and were normal at follow-up. Three of 73 infants with mild encephalopathy (BIND scores 1-3) but severe jaundice (TSB ranging 33.5-38 mg/dL; 573-650 µmol/L) had residual neurologic and/or auditory impairment. A BIND score ≥4 had a specificity of 87.3% and a sensitivity of 97.4% for predicting poor neurologic outcomes (receiver operating characteristic analysis). BIND scores trended higher with severe hyperbilirubinemia (r2 = 0.54, P < .005), but 5/39 (13%) infants with TSB ≥36.5 mg/dL (624 µmol/L) had BIND scores ≤3, and normal outcomes at 3-5 months. The BIND score can be used to evaluate the severity of acute bilirubin encephalopathy and predict residual neurologic and hearing dysfunction.

CD8+ encephalitis: a severe but treatable HIV-related acute encephalopathy

Rapidly progressive encephalopathy in an HIV-positive patient presents a major diagnostic and management challenge. CD8+ encephalitis is a severe but treatable form of HIV-related acute encephalopathy, characterised by diffuse perivascular...

Study on the cerebral hemodynamic changes by transcranial Doppler ultrasonography from emergency periods to stable periods in severe acute encephalopathy children

Objective To evaluate the correlations between the cerebral hemodynamic changes of severe acute encephalopathy with the clinical features from emergency periods to stable periods and the value of transcranial Doppler ultrasonography(TCD) in cerebral function assess. Methods Thirty patients with acute brain diseases by assisted mechanical ventilator from Jun 2014 to May 2015 in PICU were included and followed up to Nov 2015, then grouped by Glasgow Coma Scale(GCS), MRI, prognosis(mental sequelae after half a year). Each subject was examined through the temporal bone window by TCD at emergency periods and stable periods.The systolic cerebral blood flow velocity(sCBFV), and pulsatility index(PI) of bilateral middle cerebral artery(MCA), anterior cerebral artery, posterior cerebral artery were analyzed.Multivariant analysis of variance, repeated measures analysis of variance was conducted to compare sCBFV and PI of MCA among groups in different clinical periods.The variants included sex, disease diagnosis, prognosis, MRI, GCS, and the first abnormal TCD.The variation within groups was tested via a Hotelling T2 test.All sCBFV and PI of each artery and the D-value of sCBFV between the different periods were compared according to the prognosis groups. Results (1) Five patients could be lateralized, and their lateralization of MRI focus was consistent with the abnormal sides of sCBFV in the stable periods.(2) The D-value of sCBFV in left MCA between the different periods in the poor prognosis group was significantly higher than that in the good prognosis group[(71.93±58.21) cm/s vs.(33.20±30.23) cm/s, t=-2.287, P=0.033]. (3) Multivariant analysis of variance showed that GCS classification and disease diagnosis were significantly correlated with the cerebral hemodynamic changes respectively(P=0.042, 0.005, respectively). (4) sCBFV and PI of left MCA reduced significantly in the stable periods than those in the emergency periods(P=0.002, 0.003, respectivly). Conclusion The cerebral hemodynamic changes by TCD from emergency periods to stable periods are consistent with the clinical status, dynamic evaluation by TCD may facilitate the evaluation of brain dysfunction in the severe acute encephalopathy. Key words: Severe acute encephalopathy; Cerebral hemodynamic; Transcranial Doppler ultrasonography; Glasgow Coma Scale; Prognosis,

Severe acute encephalopathy related to human parainfluenza virus type 2 infection in an infant: a case report

Introduction: We present here a rare case of severe acute encephalopathy with extra-pulmonary symptoms in a two-year-old girl caused by human parainfluenza virus type 2 (HPIV2) infection. Case Presentation: The patient was brought in by ambulance, presenting with fever, hypoxia and generalized tonic-clonic seizure, and was admitted into Fukuyama Medical Center. She had a depressed level of consciousness with drowsiness. Her Glasgow coma score was 6. Based on the results of laboratory examinations, brain computed tomography, brain magnetic resonance imaging and electroencephalography, we diagnosed her with acute encephalopathy. Treatment was initiated with high-dose intravenous immunoglobulin, methylprednisolone pulse therapy and edaravone along with mechanical ventilation. We confirmed HPIV2 infection using samples of sputum from the intra-tracheal tube, throat swab and blood using next-generation sequencing and the PCR method. After continued steroid and anti-inflammatory therapy, the patient recovered completely. Conclusion: Extra-pulmonary symptoms in parainfluenza viral infections are rare. HPIV2 infection can cause severe acute encephalopathy via a systemic immunological reaction along with airway symptoms.

Severe Anti-NMDAR-Encephalitis with Extreme Movement Disorder in an 18-Month-Old Girl: Long-Term Follow-Up by Video

Introduction: If anti-N-methyl d-aspartate (NMDAR) encephalitis presents in infancy, it usually shows a clinical picture of severe acute encephalopathy with movement disorder. We documented the follow-up on a case of early-childhood anti-NMDAR-encephalitis with a relapse under second-line immunotherapy, using repeat videos. The girl improved only after an additional intensive therapy.

Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation.

Glutaric acidemia type I (GA-I) is a treatable autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Presentation and progression of disease are variable ranging from asymptomatic carrier state to catastrophic encephalopathy. GA-I usually presents before age 18months, usually triggered by childhood infection, with mild or severe acute encephalopathy, striatal degeneration, and movement disorder, most often acute dystonia. At a presymptomatic stage diagnosis is suggested clinically by macrocephaly, radiologically by widened Sylvian fissures and biochemically by the presence of excess 3-hydroxyglutaric acid and glutaric acid in urine. Treatment consists of lysine-restricted diet and carnitine supplementation, specific diet restrictions, as well as symptomatic and anticatabolic treatment of intercurrent illness. Presymptomatic diagnosis and treatment are essential to prognosis. We report the case of 16-year-old macrocephalic female with late-onset GA-I and unusual paucisymptomatic presentation with fainting after exercise and widespread white matter signal changes at MRI. She was compound heterozygote for a novel mutation (IVS10-2A>G) affecting splicing at GCDH and a common missense mutation (c. 1240C>T; p.Arg402Trp, R402W). Interestingly, the site of the novel mutation is the nucleotide position of a common mutation found almost exclusively in patients of Chinese/Taiwanese origin (IVS10-2A>C).

Adult lead encephalopathy

The neurotoxicity of lead to the adult brain is less well-known than that seen in children. It may present as acute severe encephalopathy or as chronic cognitive and behavioural symptoms, either in isolation or with systemic features of lead intoxication. Magnetic resonance imaging findings in lead encephalopathy vary. The pathogenesis of lead encephalopathy and its effects on cognition both during development and in the adult are discussed. That encephalopathic symptoms do not correlate with blood lead levels and that they may persist after chelation are highlighted. As an illustration, we describe a patient with chronic cumulative lead intoxication, who presented with peripheral neuropathy, anaemia, and a ‘lead line’ on the gingiva. She had cognitive dysfunction with extensive subcortical and cerebellar white matter lesions on magnetic resonance imaging. An area of restricted diffusion in both frontal regions is likely to be due to active ongoing demyelinating at the ‘leading edge’ of the lesion. Although systemic features and the peripheral neuropathy improved with chelation, the encephalopathy showed only marginal change, with later appearance of a symmetric akinetic-rigid state.

小児重症急性脳症における頭蓋内圧の推移に関する検討

小児重症急性脳症における頭蓋内圧の推移に関する検討