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.

Whole exome sequencing of a novel homozygous missense variant in PALB2 gene leading to Fanconi anaemia complementation group.

Partner and localiser of BRCA2 (PALB2), also known as FANCN, is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of PALB2 are associated with breast and overian cancers, while bi-allelic mutations cause Fanconi anaemia (FA). In the present study, whole exome sequencing (WES) identified a novel homozygous missense variant, NM_024675.3: c.3296C>G (p.Thr1099Arg) in PALB2 gene (OMIM: 610355) that caused FA with mild pulmonary valve stenosis and dysmorphic and atypical features, including lymphangiectasia, non-immune hydrops fetalis and right-sided pleural effusion in a preterm female baby. WES results were further validated by Sanger sequencing. WES improves the screening and detection of novel and causative genetic variants to improve management of disease. To the best of our knowledge, the present study is the first reported FA case in a Saudi family with phenotypic atypical FA features. The results support the role of PALB2 gene and pathogenic variants that may cause clinical presentation of FA. Furthermore, the present results may establish a disease database, providing a groundwork for understanding the key genomic regions to control diseases resulting from consanguinity.

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.

Adalimumab-induced central nervous system demyelination in a patient with rheumatoid arthritis.

Adalimumab (Humira) is a human monoclonal antibody that belongs to the tumor necrosis factor (TNF) alpha antagonist class of medications. Central Nervous System (CNS) demyelination is a rare side effect of adalimumab, and only a few cases have been reported in the literature of patients who developed multiple sclerosis or other demyelinating patterns after using adalimumab. In this report, we present a case of CNS demyelination in a patient with rheumatoid arthritis that developed a few months after using adalimumab. Performing brain MRI for asymptomatic individuals prior to initiating anti-TNF alpha agents to exclude a pre-existing demyelinating disease may be worthwhile. Routine brain MRI for monitoring and surveillance may facilitate detecting cases early and avoid the development of permanent neurological disability. Further studies are needed to clarify the neurological safety of anti-TNF alpha agents.

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).

Perception of the Accreditation of the National Commission for Academic Accreditation and Assessment at Different Health Colleges in Jeddah, Saudi Arabia.

Introduction Following the guidelines for maintaining quality set forth by the National Commission for Academic Accreditation and Assessment (NCAAA) accreditation procedure, Saudi higher education institutions, including health sciences colleges, must adhere to these guidelines. This study aims to assess the perception of personnel involved in NCAAA accreditation processes about the purpose, process, motivation, and level of involvement in the NCAAA accreditation at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS). Methods The study was conducted at KSAU-HS, Jeddah. The participants included 15 administrators and 32 faculties from the College of Medicine, College of Applied Medical Sciences, and College of Nursing with experience in the NCAAA process. A questionnaire was used to determine how motivated and involved people feel about the accreditation process. Data were examined statistically with SPSS (Version 23; IBM Corp., Armonk, NY, USA), and descriptive statistics were used. Results Forty-seven participants (23 men, 24 women, ages 36 to 55) took part in the study, of which 68% were faculty members and 32% were administrators with a variety of skill sets from the three colleges. Most participants displayed a positive attitude toward the NCAAA accreditation's motive and level of commitment. Conclusions Most of the participants in the current study contended with the NCAAA process and deemed it substantial long-term improvements.

Cerebral Radiation-Induced Vasculopathy Mimicking Primary Central Nervous System Vasculitis.

Cranial irradiation is one of the main treatment modalities for tumors of the CNS. However, it can lead to significant damage to the treated region. Among the late complications of radiation therapy to the brain is vasculopathy of the small and/or large arteries. In this article, we report a case of CNS radiation-induced vasculopathy presenting 30 years after cranial irradiation and mimicking primary CNS vasculitis. The present case illustrates the importance of monitoring and carefully evaluating delayed side effects of radiotherapy as well as emphasizes the importance of obtaining a detailed history of any patient presenting with sudden unexplained symptoms. If a complete proper history of the patient's past medical diagnoses and procedures was taken, medical professionals would not have needed to conduct extensive investigations and implement treatment plans for a less likely diagnosis, in this case, aggressive treatment of a possible primary CNS vasculitis with high-dose steroids. Therefore, it is imperative to raise the possibility of radiation-induced vasculopathy after excluding all possible causes of deterioration in patients with a history of cranial radiation therapy.

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.

Benefits of Space Medicine Research for Healthcare on Earth.

Space research has brought various discoveries and benefits in the fields of health, transportation, safety measures, industry, and many more. Additionally, space research has provided a large number of discoveries and inventions in the field of medicine. Many of these inventions benefit humanity in multiple ways, especially with regard to well-being. Research objectives range from the early detection of illnesses to statistical studies that help in epidemiology. Furthermore, there are potential future opportunities that might help in the development of mankind in general and Earth medicine in particular. This review presents some of the significant inventions that were made through the journey to space and elaborate on how those inventions helped develop Earth medicine and other fields.

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.

Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan.

The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the Malakand Division. METHODS: Eye colour digital photographs and buccal swab samples of 893 individuals of different age groups were collected. Multiplexed SNaPshot single base extension chemistry was used, and the genotypic results were analysed. Snapshot data were used for eye colour prediction through the IrisPlex and FROG-kb tool. RESULTS: The results of the present study found brown eye colour to be the most prevalent eye colour in comparison to intermediate and blue coloured. Overall, individuals with brown-coloured eyes possess CT (46.84%) and TT (53.16%) genotypes. Blue eye-coloured individuals are solely of the CC genotype, while individuals of intermediate eye colour carry CT (45.15%) and CC (53.85%) genotypes in rs12913832 SNP in the HERC2 gene. It was also revealed that brown-coloured eyes individuals were dominant among all age groups followed by intermediate and blue. Statistical analysis between particular variables and eye colour showed a significant p-value (<0.05) for rs16891982 SNP in SLC45A2 gene, rs12913832 SNP in HERC2 gene, rs1393350 SNP in SLC45A2, districts and gender. The rest of the SNPs were non-significant with eye colour, respectively. The rs12896399 SNP and SNP rs1800407 were found significant with rs16891982 SNP. The result also demonstrated that the study group differs from the world population based on eye colour. The two eye colour prediction results were compared, and it was discovered that IrisPlex and FROG-Kb had similar higher prediction ratios for Brown and Blue eye colour. CONCLUSIONS: The results of the current study revealed brown eye colour to be the most prevalent amongst members of the local population of Pakhtoon ethnicity in the Malakand Division of northern Pakistan. A set of contemporary human DNA samples with known phenotypes are used in this research to evaluate the custom panel's prediction accuracy. With the aid of this forensic test, DNA typing can be supplemented with details about the appearance of the person from whom the sample was taken in cases involving missing persons, ancient human remains, and trace samples. This study may be helpful for future population genetics and forensics studies.

Collection of Biospecimens from the Inspiration4 Mission Establishes the Standards for the Space Omics and Medical Atlas (SOMA).

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from the crew at different stages of the mission, including before (L-92, L-44, L-3 days), during (FD1, FD2, FD3), and after (R+1, R+45, R+82, R+194 days) spaceflight, creating a longitudinal sample set. The collection process included samples such as venous blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies, which were processed to obtain aliquots of serum, plasma, extracellular vesicles, and peripheral blood mononuclear cells. All samples were then processed in clinical and research laboratories for optimal isolation and testing of DNA, RNA, proteins, metabolites, and other biomolecules. This paper describes the complete set of collected biospecimens, their processing steps, and long-term biobanking methods, which enable future molecular assays and testing. As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can also aid future experiments in human spaceflight and space biology.

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.

Automated pupillometry in space neuroscience.

Modern pupillometers are automated, thereby providing an objective, accurate, and reliable evaluation of various aspects of the pupillary light reflex at precision levels that were previously unobtainable. There are many gaps in knowledge regarding pupil size and pupillary light reflex in nervous system changes related to space travel given the previous lack of a precise method to quantitatively measure it. Automated pupillometry has not been used previously in space. This novel tool has promising uses in altered gravity environments as a sensitive non-invasive tool to determine alterations due to headward fluid shifts and elevated intracranial pressure. This article discusses the potential use of automated pupillometry in space for monitoring of astronaut health and neurological pathology.

Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme, ST3GAL5 Gene in a Saudi Family Causing Salt and Pepper Syndrome.

Salt and pepper developmental regression syndrome (SPDRS) is an autosomal recessive disorder characterized by epilepsy, profound intellectual disability, choreoathetosis, scoliosis, and dermal pigmentation along with dysmorphic facial features. GM3 synthase deficiency is due to any pathogenic mutation in the ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5 (ST3GAL5) gene, which encodes the sialyltransferase enzyme that synthesizes ganglioside GM3. In this study, the Whole Exome Sequencing (WES) results presented a novel homozygous pathogenic variant, NM_003896.3:c.221T>A (p.Val74Glu), in the exon 3 of the ST3GAL5 gene. causing SPDRS with epilepsy, short stature, speech delay, and developmental delay in all three affected members of the same Saudi family. The results of the WES sequencing were further validated using Sanger sequencing analysis. For the first time, we are reporting SPDRS in a Saudi family showing phenotypic features similar to other reported cases. This study further adds to the literature and explains the role of the ST3GAL5 gene, which plays an important role, and any pathogenic variants that may cause the GM3 synthase deficiency that leads to the disease. This study would finally enable the creation of a database of the disease that provides a base for understanding the important and critical genomic regions that will help control intellectual disability and epilepsy in Saudi patients.

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.