COVID-19–Associated Acute Asymmetric Hemorrhagic Necrotizing Encephalopathy: A Case Report

Background: Coronavirus disease 2019 (COVID-19) has been associated with many neurological complications affecting the central nervous system. Purpose: Our aim was to describe a case of COVID-19 associated with a probable variant of acute necrotizing encephalopathy (ANE). Results: A 60-year-old man who presented with a 3-day history of dyspnea, fever, and cough tested positive for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Five days following his admission, the patient was intubated secondary to respiratory failure. Following his extubation 16 days later, he was found to have a left-sided weakness. Magnetic resonance imaging (MRI) of the brain showed hemorrhagic rim-enhancing lesions involving the right thalamus, left hippocampus, and left parahippocampal gyrus. These lesions showed decreased relative cerebral blood flow on MR perfusion and restricted on diffusion-weighted imaging. These neuroimaging findings were consistent with ANE. The left-sided weakness gradually improved over the subsequent weeks. Conclusions: We concluded that COVID-19 can be associated with ANE, a condition believed to be the result of an immune-mediated process with activation of the innate immune system. Future studies must address whether biological drugs targeting the pro-inflammatory cytokines could prevent the development of this condition.

Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury

Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-CoV-2. Affected individuals typically present with rapid changes in consciousness, focal neurological deficits, and seizures. Neuroimaging reveals symmetric, bilateral deep gray matter lesions, often involving the thalami, with evidence of necrosis and/or hemorrhage. The clinical and radiologic picture must be distinguished from direct infection of the central nervous system by some viruses, and from metabolic and mitochondrial disorders. Outcomes following ANE are poor overall and worse in those with brainstem involvement. Specific management is often directed toward modulating immune responses given the potential role of systemic inflammation and cytokine storm in potentiating neurologic injury in ANE, though benefits of such approaches remain unclear. The finding that many patients have mutations in the nucleoporin gene RANBP2, which encodes a multifunctional protein that plays a key role in nucleocytoplasmic transport, may allow for the development of disease models that provide insights into pathogenic mechanisms and novel therapeutic approaches.

Rapidly Fatal COVID-19-associated Acute Necrotizing Encephalopathy in a Previously Healthy 26-year-old Man

No abstract available. Article truncated after 150 words. A 26-year-old man presented to our Emergency Department at 0200 on the day of admission with chief complaints of subjective fever, leg myalgias, and progressive dyspnea of one week duration. An oropharyngeal swab PCR had revealed SARS-CoV-2 RNA three days previously. He had not received a SARS CoV-2 vaccination, but had made an appointment to receive it just a few days prior to the onset of his symptoms. The patient had no significant past medical history, was taking no medications except for ibuprofen and acetaminophen over the past week, and did not take recreational drugs. He specifically denied headache and had no prior history of seizure. On admission, his HR was 150 bpm (sinus), RR 22, BP 105/46 mmHg, temp 40.2° C. and SpO2 92% on room air. He was ill-appearing, but alert and oriented, his neck was supple and lung auscultation revealed bilateral rhonchi, but physical examination was otherwise …

Spontaneous Subarachnoid Haemorrhage in a Case with Covid-19 Infection - Effect or Association? A Case Report

Covid-19 is a disease caused by the SARS-CoV-2 virus that usually causes mild flu-like illness in majority of the cases, but it can cause severe pneumonia and multiple organ dysfunction even death especially in elderly patients who also have comorbidities like hypertension, diabetes, chronic obstructive airway disease (COAD), asthma, and cardiac disease. The central and peripheral nervous systems are not spared, and neurological complications are frequently reported in severely ill patients who have comorbidities. The SARS-CoV-2 virus has the potential to invade the brain and it enters the brain via a haematogenous route or olfactory system through angiotensinconverting enzyme -2 receptors, present on endothelial cells of cerebral vessels. The most neurological manifestations, seen in Covid-19 infection are altered sensorium (agitation, delirium, and coma), ischemic or haemorrhagic stroke, acute disseminated encephalomyelitis or acute necrotizing encephalopathy, headaches, Guillain-Barré syndrome. Here is a case of a 70-year-old hypertensive female who presented to us with complaints of fever, headache and vomiting of 3 days duration and after investigations, a diagnosis of Covid -19 with hypertension and subarachnoid haemorrhage was made.

Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4

Background Thiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis. Results We report three cases of encephalopathy from two unrelated pedigrees with basal ganglia signal changes after fever of unknown origin. To distinguish this from other types of encephalopathy, such as acute necrotizing encephalopathy, exome sequencing was performed, and four novel heterozygous variations, namely, c.169G>A (p.Ala57Thr), c.383C>T (p.Ala128Val), c.76G>A (p.Gly26Arg), and c.745T>A (p.Phe249Ile), were identified in SLC25A19. All variants were confirmed using Sanger sequencing. To determine the pathogenicity of these variants, functional studies were performed. We found that mitochondrial TPP levels were significantly decreased in the presence of SLC25A19 variants, indicating that TPP transport activities of mutated SLC25A19 proteins were impaired. Thus, combining clinical phenotype, genetic analysis, and functional studies, these variants were deemed as likely pathogenic. Conclusions Exome sequencing analysis enables molecular diagnosis as well as provides potential etiology. Further studies will enable the elucidation of SLC25A19 protein function. Our investigation supplied key molecular evidence for the precise diagnosis of and clinical decision-making for a rare disease.

BEND4 as a Candidate Gene for an Infection-Induced Acute Encephalopathy Characterized by a Cyst and Calcification of the Pons and Cerebellar Atrophy

Three siblings born to Turkish parents from the same village had normal brain development until acute neurological deterioration between 12 months and 8 years of age. Consequent loss of all acquired motor, social, and language functions following infections was associated with a pontine cyst, calcification, and cerebellar atrophy. Exome sequencing revealed a homozygous c.1297G&#x3e;A (p.Gly433Ser) alteration in <i>BEND4</i>, which was predicted to be deleterious in in silico analysis tools and segregated in multiple affected individuals in the family. <i>BEND4</i> has not been associated with any existing disease. Immunofluorescence microscopy analysis of wild-type and mutant BEND4 expressing Vero cells showed nuclear and cytoplasmic localization. Wild-type BEND4 displayed a network-like distribution, whereas mutant BEND4 showed a juxtanuclear distribution pattern. Differential proteome analysis of Vero cells expressing BEND4 revealed that mutant BEND4 expression caused selective increase in reticulocalbin-1 and endoplasmic reticulum resident protein-29. Both proteins are associated with the endoplasmic reticulum and are primarily involved in protein processing and folding pathways. Any defect or stress in protein folding creates stress on cells and may cause chronic damage. This is the first study showing that pathogenic <i>BEND4</i> variants may lead to an infection-induced acute necrotizing encephalopathy as demonstrated in characteristic neuroimaging findings.