Hypoventilation and progressive encephalopathy in a neonate with MTHFR deficiency

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive inherited inborn error of metabolism, which presents with various severity depending on the level of residual enzyme activity. In neonates, it can present with recurrent hypoventilation episodes, persistent encephalopathy with or without microcephaly. MTHFR deficiency also results in hyperhomocysteinemia, homocystinuria and hypomethionemia. We report a male neonate with severe MTHFR deficiency presenting to us on third week of life with progressive encephalopathy, microcephaly, seizures, central hypoventilation. There was similar history in the previous sibling. The patient’s blood lactate, ammonia, tandem mass spectrometry for amino acids and acyl carnitine were normal. He remained encephalopathic with progressive increase in need of respiratory support in spite of supportive treatment and metabolic cocktail consisting of riboflavin, pyridoxine, coenzyme Q and carnitine. This neonate had novel homozygous mutation, which results in MTHFR deficiency. In newborn with hypoventilation or recurrent apnoea with encephalopathy and microcephaly, MTHFR deficiency should be considered as a differential diagnosis. Mutation study helps in confirming diagnosis; however, extended newborn metabolic screening with homocysteine level could help in early diagnosis of these cases.

OUTCOMES OF REFRACTORY STATUS EPILEPTICUS IN CHILDREN

Objective: To determine the outcome of Refractory Status Epilepticus (RSE) in children and the factors affecting the outcome. Study Design: Cross-sectional study. Place and Duration of Study: High Dependency Unit of Pediatrics Neurology Department at the Children’s Hospital and Institute of Child Health, from Aug 2019 to Mar 2020. Methodology: This study was conducted on the children presenting with refractory status epilepticus. Structured proforma was used for recording predictive factors. Modified Rankin scale prior to the presentation and Glasgow Coma Scale at presentation were documented and compared with the discharge scores. Results: Out of 75 children, 46 (61.4%) were males with mean age of 4.43 ± 3.47 years. Common etiologies were acute symptomatic in 37 (49.3%), progressive encephalopathy in 19 (25.3%), static encephalopathy in 9 (11.9%), remote symptomatic in 4 (5.3%), acute on remote symptomatic in 3 (4.0%), idiopathic and unclassified in remaining patients. Mean time between seizures onset and first benzodiazepine injection was 44 ± 36 minutes. Duration of RSE was <24 hours in 17 (22.7%), 24-48 hours in 15 (20.0%), 48-72 hours in 14 (18.6%), 72-96 hours in 12 (16%) and >96 hours in 17 (22.7%). At discharge 33 (44%) returned to baseline, 31 (41%) developed neurological disability while 11 (15%) expired during the stay. Etiology and duration of status epilepticus had significant impact on outcome with p-value of 0.021 and 0.041, respectively. Conclusion: Acute etiology was associated with higher mortality whereas return to baseline was also fair among survivors. This poses implications for emergency management to significantly............

Close patient observation and electroencephalography play an important role in the diagnosis of rare diseases. Presentation of a case of Creutzfeldt-Jakob disease

Creutzfeldt–Jakob disease is a rare, progressive spongiform encephalopathy caused by infectious proteins called prions. It is characterised by rapidly progressive dementia accompanied by cerebellar, visual, extrapyramidal, and pyramidal symptoms, as well as myoclonus and mutism in later stage of the disease. The most common type is sporadic Creutzfeldt– Jakob disease, accounting for 85% of all cases. Treatment of the disease is symptomatic. An important role in making the diagnosis is attributed to the observation of the patient and electroencephalography, showing characteristic cyclical discharges. We present the case of a patient whose first symptoms were psychiatric in nature, and who was diagnosed with Creutzfeldt–Jakob disease based on careful observation, presence of myoclonus, and repeated electroencephalography examinations in which typical 1–2 seconds of sharp and slow wave discharges appeared. By presenting this case of severe progressive encephalopathy, we would like to highlight the fact that even in the age of modern diagnostic methods, electroencephalography, which has been in use for many years, may be crucial in the diagnostic process. We would also like to point out that the initial symptoms of Creutzfeldt–Jakob disease may suggest a psychiatric disorder.

NCMP-16. MANAGEMENT AND LONG-TERM OUTCOMES OF PATIENTS WITH RECURRENT STROKE-LIKE EPISODES AFTER CRANIAL RADIOTHERAPY

Stroke-Like Migraine Attacks after Radiation Therapy (SMART) is a descriptive clinical entity consisting of transient hemispheric dysfunction. We were interested in pragmatic management patterns for patients with Recurrent Stroke-Like Episodes (R-SLE) of transient negative neurologic symptoms after cranial radiotherapy (RT) to define optimal management strategy and assess long-term outcomes. We conducted a retrospective review of all patients with recurrent negative neurologic symptoms after cranial RT who were treated at Mayo Clinic (Rochester), with follow-up extending until February 2021. Descriptive statistics and Chi-Square analysis was performed to assess for differences between patients with clinical cessation of symptoms, death, progressive encephalopathy and therapeutic class, patient and primary treatment characteristics (i.e. whole brain RT). We identified 27 patients with R-SLE after RT. 25 patients were included in analyses. Median age at diagnosis was 28.7 years (3.0-65.8 years, SD: 15.0 years). Median time from RT to symptom onset was 14.6 years (3.3-30.5 years, SD: 8.9 years). The most common presentations included hemiparesis (55.6%), hemisensory loss (22.2%), transient visual field loss (33.3%), encephalopathy (18.5%), and aphasia (22.2%). Antiseizure medications were most used for management of R-SLE (92%) followed by anti-platelets (68%), verapamil (52%), statins (48%), glucocorticoids (24%), antivirals (20%), and ACE inhibitors/angiotensin receptor blockers (16%). Beta blockers were not used. Verapamil use was frequently associated with clinical cessation of recurrent events with cessation being achieved in 64.7% of patients on verapamil versus 35.3% not on verapamil (p=0.0638). Other medical interventions did not approach clinical or statistical significance. Progressive encephalopathy was more common in patients without clinical cessation (87.5% vs. 23.5%, p=0.0026). All patients who died at last follow-up had progressive encephalopathy. We found cessation of recurrent negative neurologic symptoms after cranial RT in most patients. Verapamil use was associated with clinical cessation. Progressive encephalopathy was more common in patients without clinical cessation of recurrent events.

Tumefactive Acute Disseminated Encephalomyelitis after Recent Covid-19 Infection: A Case Report

Objective: To report a case of a patient with recent mild to moderate COVID-19 infection who developed tumefactive acute disseminated encephalomyelitis. Methods: Patient data were obtained from medical records from the University of Wisconsin – Madison Hospitals in Madison, WI, USA. Results: We report a 59-year-old man with past medical history notable for atrial fibrillation, biventricular pacemaker, end-stage renal disease secondary to idiopathic fibrillary glomerulonephritis, on hemodialysis awaiting transplantation, who presented with ongoing cognitive changes and pneumonia. He was repeatedly COVID-19 positive with minimal symptoms for 4 weeks prior to admission. He developed right sided hemiparesis and persistent, progressive encephalopathy manifesting primarily with disorientation, agitation, and aggression. CSF was notable for cell count of 7, protein of 48, and glucose of 65. Anti-MOG antibody and AQP-4 antibody were negative. A series of CT/CTA head imaging with and without contrast showed progressive multifocal supratentorial areas of white matter hypoattenuation and MRI head with and without contrast demonstrated progressive multi-focal large ovoid T2 FLAIR hyperintensities, partially ring enhancing on contrasted portion of study, consistent with tumefactive demyelinating disease. Significant improvement in mental status and right sided hemiparesis symptoms was observed with initiation of corticosteroids. Conclusion: This case study provides neuroimaging evidence and clinical correlation to support that SARS–CoV-2 and resultant COVID-19 infection can lead to tumefactive acute disseminated encephalomyelitis. This complication has not been previously documented associated with recent COVID-19 infection.

Relevance of Brain 18F-FDG PET Imaging in Probable Seronegative Encephalitis With Catatonia: A Case Report

Autoimmune encephalitis (AIE) is a rare, severe, and rapidly progressive encephalopathy, and its diagnosis is challenging, especially in adolescent populations when the presentation is mainly psychiatric. Currently, cerebral 18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) imaging is not included in the diagnosis algorithm. We describe a 16-year-old patient with probable seronegative encephalitis with catatonia for which several cerebral PET scans were relevant and helpful for diagnosis, treatment decision making, and follow-up monitoring. The patient recovered after 2 years of treatment with etiologic treatment of AIE and treatment of catatonia. This case suggests a more systematic assessment of the clinical relevance of 18F-FDG-PET imaging in probable seronegative AIE.

Endodontic Treatment in a single session in a patient with Chronic Non-Progressive Encephalopathy: Case report

This study aims to report a one-session endodontic treatment of a patient with chronic Non-progressive encephalopathy (CNPE). A patient with CNPE attended our postgraduate clinic for patients with special needs. During the anamnesis, the patient's brother, who is his legal representative, reported discomfort with the esthetics of the patient's anterior tooth and that the patient felt discomfort when touching the same dental element. After detailed anamnesis and elaboration of the treatment plan, endodontic treatment of element 11 (upper right central incisor) and coronary reconstruction were performed. Taking care of patients with cerebral palsy is still a challenge in dentistry. This is because care has to be taken when carrying out necessary interventions in these patients. This treatment aims at the positive resolution of their pathological condition and well-being. The possibility of endodontic treatment in a single session makes treatment more humane and less mutilating.

Autoimmune Encephalitis in Tunisia: Report of a Pediatric Cohort

Background. Autoimmune encephalitis (AE) is a rapidly progressive encephalopathy caused by antibodies targeting neurons in the central nervous system generating specific immune responses. It is increasingly recognized in children. Objective. To describe clinical, neuroimaging, and laboratory features, treatment, and outcome in a cohort of Tunisian children with AE. Methods. We conducted a retrospective review of the medical records of all children attending the Department of Child and Adolescent Neurology (Tunis) with autoimmune encephalitis between 2004 and 2020. Clinical, neuroimaging, laboratory features, therapeutic data, and outcome were analyzed. Results. Nineteen children were included in the study (12 girls and 7 boys). The median age at diagnosis was 7.68 years (range: 10 months-13 years). The most frequent manifestations were seizures and behavioral disorders. Eleven cases were diagnosed with anti-NMDA receptor encephalitis, 4 cases with anti-Ma2 encephalitis, 3 cases with anti-GAD encephalitis, and 1 case with anti-SOX1 encephalitis. Brain MRI showed increased T2 and fluid-attenuated inversion recovery (FLAIR) signal of the temporal lobe in 5 patients. Eighteen patients showed improvement following first-line immunotherapy (high-dose corticosteroids, intravenous immunoglobulin). One patient with anti-GAD encephalitis died despite escalating immunotherapy. Conclusion. Diagnosis of autoimmune encephalitis is challenging in children, because of misleading presentations. An early and accurate diagnosis is important to enable proper therapeutic interventions.

Celia’s Encephalopathy (BSCL2-Gene-Related): Current Understanding

Seipin, encoded by the BSCL2 gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in BSCL2 can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia’s encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in BSCL2 associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia’s encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorder.