Laughter-Induced Seizures: A Rare Type of Reflex Epilepsy.

This research explores the rare occurrence of laughter-induced seizures, a form of reflex epilepsy documented in only one previous case in the literature. The patient, free from prior medical or neuropsychiatric history, exhibited seizures triggered solely by laughter. Electroencephalography and neuroimaging revealed normal results. Despite declining medical therapy, lifestyle modifications enabled seizure management. The study emphasizes the dearth of data on laughter-induced seizures, prompting the consideration of multimodal strategies for treatment. Further research is imperative to unveil the precise pathophysiology and establish standardized therapeutic approaches for this uncommon epileptic manifestation.

Insights into adjunctive corticosteroid therapy in fulminant herpes simplex virus encephalitis: case analysis with contrasting outcomes.

Herpes simplex virus (HSV) encephalitis, predominantly caused by HSV-1, presents with significant morbidity and mortality challenges. This research investigates the particular role of adjunctive corticosteroid therapy in fulminant HSV encephalitis through in-depth analyses of two contrasting cases. Corticosteroids show potential benefits to improve an exaggerated immune response and limit viral dissemination within the brain. Daily assessments and frequent neuroimaging, particularly using magnetic resonance imaging, aid in the management of fulminant cases. Although existing evidence relies on limited case series and retrospective comparisons, the results of the present study emphasize the necessity for large-scale controlled trials to establish definitive guidelines. The discretion of the treating neurologist governs the decision to implement corticosteroids, emphasizing the imperative need for continued research and evidence-based strategies for this challenging neurological condition.

Autosomal recessive spinocerebellar ataxia type 4 due to a novel homozygous mutation in the VPS13D gene in a Saudi family.

Vacuolar protein sorting 13 homolog D (VPS13D) gene encodes a protein involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. This study reports a novel homozygous mutation (c.12494T>C p.Ile4165Thr) in the VPS13D gene in a Saudi female diagnosed with autosomal recessive spinocerebellar ataxia type 4 (SCAR4). The patient's clinical presentation, including progressive weakness, ataxia, and numbness, aligns with SCAR4 characteristics. The comprehensive evaluation, comprising neurological examination, brain MRI, and genetic testing, revealed distinctive features consistent with autosomal recessive inheritance. The genetic mutation spectrum enrichment emphasizes the intricate interplay of genetic factors in SCAR4. Although no specific treatment exists, rehabilitation and supportive therapy remain central. The identified mutation contributes valuable insights for clinical management and genetic counseling, urging the ongoing collection of VPS13D gene mutation data to explore genotype-phenotype correlations in spinocerebellar ataxias. This study underscores the importance of multidisciplinary care and lays the foundation for future research directions in understanding and treating SCAR4.

Primordial and Primary Prevention of Ischemic Stroke in Saudi Arabia: A Combination Approach and Evolving Concepts.

Ischemic stroke is a considerable public health hazard and a significant cause of disability and mortality in Saudi Arabia. Primary prevention strategies in the country are currently limited. With the health sector transformation program that depends on the principles of value-based care and applying the new model of care in disease prevention, aggressive and serious steps for primary stroke prevention are expected to be implemented. This article reviews primordial and primary prevention of ischemic stroke in Saudi Arabia and suggests a combination approach and framework for implementation. We provide a pragmatic solution to implement primordial and primary stroke prevention in Saudi Arabia and specify the roles of the government, health professionals, policymakers, and the entire population. Currently, there are several key priorities for primordial and primary stroke prevention in Saudi Arabia that should target people at different levels of risk. These include an emphasis on a comprehensive approach that includes both individual and population-based strategies and establishing partnerships across health-care providers to share responsibility for developing and implementing both strategies. This is an urgent call for action to initiate different strategies suggested by experts for primary stroke prevention in Saudi Arabia.

Leber hereditary optic neuropathy presenting as bilateral visual loss and white matter disease.

Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disorder that typically affects young male adults in their second and third decades of life. It usually manifests as painless, subacute, progressive, bilateral vision loss, with more than 90% of affected individuals losing their vision before age 50. Compared with other diseases that cause optic neuritis (multiple sclerosis or neuromyelitis optica spectrum disorders), LHON has worsening visual function in the first 6-12 months of disease progression, is predominantly male, the optic nerve is affected bilaterally from onset, there is no gadolinium enhancement on MRI, no response to disease-modifying therapy, and there is a family history of mutation in mitochondrial DNA. In this article, we describe an interesting and challenging case of LHON due to a homoplasmic variant in the MT -CO3 gene that was initially misdiagnosed as a monophasic demyelinating disorder (clinically isolated syndrome vs acute disseminated encephalomyelitis vs neuromyelitis optica spectrum disorders).

Neuro-Behcet's disease misdiagnosed and treated as multiple sclerosis: a deceiving masquerader.

Behcet's disease is a chronic polysymptomatic systemic vasculitis disorder of unknown etiology characterized by several clinical manifestations in multiple organ systems. Involvement of the nervous system occurs in ∼9% of patients with Behcet's disease (ranging from 3 to 30%). Neuro-Behcet's disease is a great masquerader of multiple sclerosis. Diagnosing this disorder might be challenging, especially in a patient who does not fulfill the criteria of Behcet's disease while having a neurological presentation. We report a case of neuro-Behcet's disease who was misdiagnosed as having multiple sclerosis for many years and started on unnecessary disease-modifying therapy for multiple sclerosis. A thorough history, physical examination, and systematic investigations are mandatory to differentiate between these two conditions. Our case presentation raises awareness of the importance of differentiating between these two conditions since the consequences of misdiagnosis are catastrophic. The main challenges differentiating between multiple sclerosis and neuro-Behcet's are clinical and paraclinical, including neuroimaging.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): A challenging diagnosis and a rare multiple sclerosis mimic.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an extremely rare hereditary cerebral small vessel disease caused by homozygous or compound heterozygous mutations in the gene coding for high-temperature requirement A serine peptidase 1 (HtrA1). Given the rare nature of the disease, delays in diagnosis and misdiagnosis are not uncommon. In this article, we reported the first case of CARASIL from Saudi Arabia with a novel homozygous variant c.1156C>T in exon 7 of the HTRA1 gene. The patient was initially misdiagnosed with primary progressive multiple sclerosis and treated with rituximab. CARASIL should be considered in the differential diagnosis of patients with suspected atypical progressive multiple sclerosis who have additional signs such as premature scalp alopecia and low back pain with diffuse white matter lesions in brain MRI. Genetic testing is important to confirm the diagnosis.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Atypical clinical presentation with isolated frontotemporal dementia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary syndrome caused by heterozygous mutations in the NOTCH3 gene that manifests in adulthood and is characterized by recurrent transient ischemic attacks and strokes, migraine-like headaches, psychiatric disturbance, and progressive dementia. The current study reports an interesting case of CADASIL in a Saudi patient with a heterozygous mutation in exon 18 of the NOTCH3 gene presenting only with cognitive decline without migraine or stroke. The diagnosis was suspected mainly because of the typical brain magnetic resonance imaging (MRI) features that led to performing genetic testing to confirm the diagnosis. This illustrates the importance of brain MRI in the diagnosis of CADASIL. Increased awareness of neurologists and neuroradiologists about the typical MRI features of CADASIL is of paramount importance to reach the diagnosis in a timely manner. Awareness of the atypical presentations of CADASIL will lead to identifying more CADASIL cases.

Guillain-Barré Syndrome Following the BNT162b2 mRNA COVID-19 Vaccine.

PURPOSE: The onset of the COVID-19 (SARS-CoV-2) pandemic in December 2019 created the need for multiple scientific research activities and clinical trials in an attempt to find solutions to mitigate the impact of the virus. One of the important tools to combat the virus is the development of vaccination programs. All types of vaccines have been associated with a mild to severe risk of neurological adverse events. One of these severe adverse events is Guillain-Barré syndrome. CASE REPORT: Here, we describe a case of Guillain-Barré syndrome after the first dose of the BNT162b2 mRNA COVID-19 vaccine and review the literature to increase the current knowledge regarding this complication. CONCLUSION: Guillain-Barré syndrome after COVID-19 vaccination is responsive to treatment. The benefits of administering the vaccine outweigh the risks. Due to the negative impact of COVID-19, it is essential to recognize the development of neurological complications that are potentially associated with vaccination, including Guillain-Barré syndrome.

Hyperferritinemia with iron deposition in the basal ganglia and tremor as the initial manifestation of follicular lymphoma.

Iron is an essential element for brain cells that is required for the transport of oxygen, energy generation, myelin synthesis, and production of neurotransmitters. Disturbances in the homeostatic mechanisms of iron metabolism may cause iron accumulation with subsequent oxidative stress and cellular damage. It is important to consider the possibility of both a genetic and acquired iron overload syndrome in patients with neurological symptoms and hyperferritinemia. In this article, we are reporting a unique case characterized by hyperferritinemia with widespread deposition of iron in more than one bodily organ, movement disorder, and hidden malignancy. We stress on the importance of early diagnosis using a systematic approach since early treatment with iron chelators is warranted to prevent the progression of neurological symptoms. Even those patients who have no neurological symptoms with high iron should be monitored closely and treated early to avoid the deposition of iron in the brain. Whether brain damage and MRI changes are reversible completely or partially is a subject for further research.

Cerebral fat embolism syndrome: diagnostic challenges and catastrophic outcomes: a case series.

Fat embolism syndrome is a rare but alarming, life-threatening clinical condition attributed to fat emboli entering the circulation. It usually occurs as a complication of long-bone fractures and joint reconstruction surgery. Neurological manifestations usually occur 12 to 72 hours after the initial insult. These neurological complications include cerebral infarction, spinal cord ischemia, hemorrhagic stroke, seizures, and coma. Other features include an acute confusional state, autonomic dysfunction, and retinal ischemia. In this case series, we describe three patients with fat embolism syndrome who presented with atypical symptoms and signs and with unusual neuroimaging findings. Cerebral fat embolism may occur without any respiratory or dermatological signs. In these cases, diagnosis is established after excluding other differential diagnoses. Neuroimaging using brain magnetic resonance imaging is of paramount importance in establishing a diagnosis. Aggressive hemodynamic and respiratory support from the beginning and consideration of orthopedic surgical intervention within the first 24 hours after trauma are critical to decreased morbidity and mortality.

Adult-Onset Hereditary Spastic Paraplegia 15 in a Saudi Patient with A Compound Heterozygous Variant in the ZFYVE26Gene.

Hereditary spastic paraplegia (HSP) 15 is an autosomal recessive neurodegenerative disease caused by homozygous or heterozygous point mutations in the ZFYVE26 gene that encodes the spastizin protein, located on chromosome 14q22-q24. Hereditary spastic paraplegia has been rarely reported in Saudi Arabia. In this article, we reported a rare case of adult-onset HSP 15 with a pure form of the disease in a Saudi patient with a compound heterozygous variant in the ZFYVE26 gene. The present case suggests that a compound heterozygous mutation in the ZFYVE26 may be associated with a later-onset disease and a milder phenotype. Given the low prevalence of the disease as well as heterogenicity and variability of its presenting symptoms, HSP 15 may be difficult to diagnose. However, early diagnosis is important to prevent unnecessary extensive investigations, facilitate early symptomatic management and provide genetic counseling for family planning to those affected and their first and second-degree relatives.

Epilepsy and Hearing Loss in a Patient with a Rare Heterozygous Variant in the CACNA1H Gene.

The calcium voltage-gated channel subunit alpha 1 H (CACNA1H) is a gene present in eukaryotic cells located on chromosome 16 that encodes the T-type calcium channels, which are important for calcium influx and depolarization of cells. Pathogenic variants in CACNA1H cause autosomal dominant susceptibility to idiopathic generalized epilepsy 6 (OMIM: 611942), which is a broad term that encompasses several common seizure phenotypes. In this article, we reported a Saudi female with a heterozygous variant in the CACNA1H gene (OMIM: 607904) who had epilepsy and hearing loss. This is the first case to report the association of epilepsy and hearing loss with a variant in CACNA1H. We believe that variant may be the reason for developing both epilepsy and sensorineural hearing loss. Further studies are needed to identify the role of CACNA1H in the physiology of the ear to allow for a better understanding of the effects of mutations. In children who present with early childhood hearing loss, genetic studies in highly selected cases including those with a strong family history of hearing loss and epilepsy may help detect a CACNA1H variant early and help with the early screening and diagnosis of other associated disorders including subclinical epilepsy.

Whole-Exome Sequencing Identifies Novel SCN1A and CACNB4 Genes Mutations in the Cohort of Saudi Patients With Epilepsy.

Epilepsy is a neurological disorder described as recurrent seizures mild to severe convulsions along with conscious loss. There are many different genetic anomalies or non-genetic conditions that affect the brain and cause epilepsy. The exact cause of epilepsy is unknown so far. In this study, whole-exome sequencing showed a family having novel missense variant c.1603C>T, p. Arg535Cys in exon 10 of Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) gene. Moreover, targeted Sanger sequencing analysis showed c.1212A>G p.Val404Ile in SCN1A gene in 10 unrelated patients and a mutation in Calcium Voltage-Gated Channel Auxiliary Subunit Beta 4 gene where one base pair insertion of "G" c.78_79insG, p.Asp27Glyfs*26 in the exon 3 in three different patients were observed from the cohort of 25 epileptic sporadic cases. The insertion changes the amino acid sequence leading to a frameshift mutation. Here, we have described, for the first time, three novel mutations that may be associated with epilepsy in the Saudi population. The study not only help us to identify the exact cause of genetic variations causing epilepsy whereas but it would also eventually enable us to establish a database to provide a foundation for understanding the critical genomic regions to control epilepsy in Saudi patients.

Novel Heterozygous Variants in the HLA-DRB1 Gene in a Saudi Family With Early-Onset Familial Multiple Sclerosis: Therapeutic Failure and Success.

Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system. Familial MS is arbitrarily defined as a type of MS that runs in families with 1 or more first- to third-degree relatives in addition to the index case affected by MS. The aim of this article is to report a unique case of familial MS from Saudi Arabia with 2 novel variants in the HLA-DRB1 gene that may contribute to the pathogenesis. We observed an unfavorable response to interferon therapy and successful treatment using fingolimod therapy. This observation needs further study, including whether this lack of response is specific to interferon treatment or possibly a chance occurrence. This family work-up illustrates the importance of genetic testing in identifying variants associated with familial MS, especially if more than 2 members of the same family are affected. Although this genetic tool is used mainly for research purposes, it had clinical implications for our patient, including the appropriate selection of disease-modifying therapy and prognostic counseling. Further large-scale studies are needed to expand the genetic spectrum of familial MS with clinical and pharmacologic correlation.

Clinical whole exome sequencing revealed de novo heterozygous stop-gain and missense variants in the STXBP1 gene associated with epilepsy in Saudi families.

Intellectual disability and developmental encephalopathies are mostly linked with infant epilepsy. Epileptic encephalopathy is a term that is used to define association between developmental delay and epilepsy. Mutations in the STXBP1 (Syntaxin-binding protein 1) gene have been previously reported in association with multiple severe early epileptic encephalopathies along with many neurodevelopmental disorders. Among the disorders produced due to any mutations in the STXBP1 gene is developmental and epileptic encephalopathy 4 (OMIM: 612164), is an autosomal dominant neurologic disorder categorized by the onset of tonic seizures in early infancy (usually in the first months of life). In this article, we report two Saudi families one with de novo heterozygous stop-gain mutation c.364C > T and a novel missense c. 305C > A p.Ala102Glu in exon 5 of the STXBP1 gene (OMIM: 602926) lead to development of epileptic encephalopathy 4. The variants identified in the current study broadened the genetic spectrum of STXBP1 gene related with diseases, which will help to add in the literature and benefit to the studies addressing this disease in the future.

Acute cervical dystonia following the BNT162b2 mRNA COVID-19 vaccine.

The coronavirus disease of 2019 (COVID-19) pandemic is caused by a novel coronavirus SARS-Cov-2. Four major vaccine types are being used to fight against this deadly pandemic and save precious human lives. All types of vaccines have been associated with a risk of neurological complications ranging from mild to severe. Cervical dystonia occurring after a COVID-19 vaccine was not previously reported in the literature. In this article, we describe a case of acute cervical dystonia occurring after the first dose of the BNT162b2 COVID-19 vaccine. We attribute the occurrence of cervical dystonia to the vaccine due to the temporal relationship. This report adds to the literature a possible rare side effect of a COVID-19 vaccine and contributes to the limited literature on potential neurological side effects of mRNA-based vaccines. The likely mechanism is autoimmune. Further research is needed to probe and study the exact mechanism.