Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.

BACKGROUND: Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. METHODS: This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. RESULTS: Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339-6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. CONCLUSION: This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases.

Orbital mucormycosis - Post SARS-CoV-2 sequelae.

Multisystem involvement has not been uncommon in SARS-CoV-2 infection. There has been reports of devastating neurological complication both during and after the infection. Here we present a rare case of sino-orbital mucormycosis, diagnosis of which was confirmed on histopathology. Our patient presented with headache, 18 days after her recovery from SARS-CoV-2 infection and was extensively worked up for the cause. Initially she was treated as a severe sinusitis but failure to response to antibiotics treatment warranted for further investigations and imaging. Our patient had to undergo right eye enucleation plus debridement under general anesthesia. She is currently on anti-fungal treatment as advised by infectious disease department.

Neurological complications of SARS-CoV-2: A single-center case series authors.

The neurological manifestations of SARS-CoV-2 are wide-ranging from simple headache to severe demyelinating brain disease. This is a review of collected case reports of patients with SARS-CoV-2 with neurological manifestations presenting to the Pakistan Institute of Medical Sciences (PIMS). Neurological manifestations associated with SARS-CoV-2 such as encephalitis, acute cerebrovascular disease, encephalitis with chorea, post-COVID myositis and Guillain-Barré Syndrome (GBS) are of great concern but are often overlooked in the presence of life-threatening abnormal vital signs in severely ill SARS-CoV-2 patients. There is a need to diagnose these manifestations at the earliest opportunity to limit long-term consequences and complications. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from the cerebrospinal fluid (CSF) or the brain tissue of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.

Subarachnoid hemorrhage secondary to forceful sneeze.

Subarachnoid hemorrhage (SAH) is a relatively less common but important neurological condition comprising 5% of all the cerebrovascular accidents. In most populations the reported incidence is 6-7 per 100,000 person-years and one-third of survivors become dependent. It is a serious but potentially treatable cause of neurological morbidity. Multiple authors have identified the most unusual novel associations and triggers of subarachnoid bleeds over the past decade. We herein report a rare case of subarachnoid hemorrhage leading to focal neurological deficit in a middle aged man secondary to forceful sneeze.