BMC Neurology最新文献

{"title":"Exploring the phenotypic and genotypic spectrum of spinal muscular atrophy in Bangladeshi children.","authors":"Jobaida Parvin, Husnea Ara Khan, Narayan Chandra Saha, Seikh Azimul Hoque, Mohammad Monir Hossain, Dipa Saha, Nusrat Shams","doi":"10.1186/s12883-026-04946-x","DOIUrl":"https://doi.org/10.1186/s12883-026-04946-x","url":null,"abstract":"<p><p>Spinal muscular atrophy (SMA) is a monogenic neuromuscular disorder caused by SMN1 gene deletion and classified by clinical severity. The objective of this study was to evaluate the genotypic and phenotypic spectrum in SMA in Bangladeshi children.This cross-sectional prospective study was conducted in Pediatric Neurology Department, National Institute of Neurosciences and Hospital of Bangladesh from January 2019 and December 2022. A total of sixty four cases with clinically suspected SMA were enrolled. Genetic confirmation was done using MLPA.Genetic confirmation was achieved in 48 (75%) patients. Homozygous deletion of SMN1 exons 7 and 8 was detected in 44 (68.75%) cases, while isolated exon 7 deletion was found in 4 (6.25%) cases. No deletion was identified in 16 (25%) cases. Among genetically confirmed patients, SMA type I was most common (54%), followed by type II (40%) and type III (6%). The mean age of onset was significantly earlier in SMA type I compared with types II and III (p < 0.05). A significant inverse correlation was observed between SMN2 copy number and disease severity (Spearman's rho = 0.825, p < 0.001). Most type I patients had two SMN2 copies, whereas type II and III patients predominantly had three or more copies. Respiratory complications and mortality were predominantly in type I patients. Two patients received risdiplam and two underwent gene replacement therapy (onasemnogene abeparvovec).In conclusion, A significant genotype-phenotype correlation exists between SMN2 copy number and clinical severity among Bangladeshi children with SMA. Limited access to disease-modifying therapy highlights the need for early diagnosis and improved treatment accessibility in resource-limited settings.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between homocysteine and post-stroke depression in patients with spontaneous intracerebral hemorrhage.","authors":"Chao Zhang, Guojuan Chen, Peng Ding, Lei Xiang, Wei Yue","doi":"10.1186/s12883-026-04951-0","DOIUrl":"https://doi.org/10.1186/s12883-026-04951-0","url":null,"abstract":"<p><strong>Introduction: </strong>Depression after a stroke is the most frequent and burdensome neuropsychiatric post-stroke complication. This study aimed to determine the relationship between post-stroke depression (PSD) and the levels of homocysteine (HCY) in patients with spontaneous intracerebral hemorrhage (SICH).</p><p><strong>Method: </strong>We collected data from patients with hemorrhagic stroke (HS) admitted to the hospital and recorded their demographic and clinical characteristics. We also searched for information regarding HAM-D₁₇ (Hamilton Depression) scores and HCY levels at 3 m, the use of antidepressant medications and folic acid during the follow-up period in the group of patients diagnosed with PSD and hyperhomocysteinemia (HHcy) in the acute phase.</p><p><strong>Result: </strong>A total of 1,852 patients were included. 642 (34.7%) patients with PSD and 598 (32.3%) patients with HHcy, 364 (19.7%) patients with both conditions. A link between depression and low HCY level has similarly been found in patients with HS (OR, 1.549; 95% CI, 1.358-1.768). Additionally, left-sided stroke, anterior circulatory stroke, intraventricular hemorrhage, symptoms of paralysis or dysarthria, and higher NIHSS scores occurred more often in the PSD group. Compared to the antidepressant medications (ADM) group, HAM-D₁₇ scores decreased significantly in the ADM plus folic acid group at the end of 3 m (P = 0.036).</p><p><strong>Conclusion: </strong>On the basis of our data, PSD was significantly more frequent in patients with HHcy in patients with SICH at the acute phase. The location of hemorrhage and the severity of the disease are significantly correlated with the incidence of PSD. Oral doses of folic acid and ADM showed significant improvements in the HAM-D₁₇ scores for the patients with comorbid PSD and HHcy.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified Berlin Score for predicting sleep apnea in patients with acute ischemic stroke.","authors":"Augustus Ck Wong, Yi-Sin Wong, Sheng-Feng Sung, Chi-Shun Wu, Yu-Hsiang Su, Mao-Hsun Lin, Chien-Yu Su, Cheung-Ter Ong","doi":"10.1186/s12883-026-04873-x","DOIUrl":"https://doi.org/10.1186/s12883-026-04873-x","url":null,"abstract":"<p><strong>Background: </strong>Sleep-disorder breathing is common among ischemic stroke patients. It associated with increasing risk of stroke and poor functional outcome after stroke. Polysomnography (PSG) is the diagnostic standard but the application for acute stroke patients is limited. The Berlin Questionnaire (BQ) is a tool used for screen obstructive sleep apnea in general population, however, the diagnostic accuracy in acute ischemic stroke patients is inconsistent.</p><p><strong>Objects: </strong>The study aims to explore the accuracy of Berlin Questionnaire (BQ) for detecting the sleep apnea for acute ischemic stroke patients, using home-based sleep apnea testing as a reference. We compare the accuracy between BQ and a modified BQ.</p><p><strong>Methods: </strong>We conducted a prospective observational study between March 2023 and February 2025 at a teaching hospital in central Taiwan. Patients aged 20-85 years with MRI-confirmed acute ischemic stroke admitted within 48 h of onset were included. Each participant completed the Berlin Questionnaire and underwent home-based sleep apnea testing (Alice NightOne, Philips Respironics). Sleep apnea severity was defined by the respiratory event index (REI). The accuracy of BQ and mBQ in predicting moderate-to-severe sleep apnea (REI ≥ 15) was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).</p><p><strong>Results: </strong>Forty-six patients completed both assessments. Twenty-one patients (45.7%) had no or mild sleep apnea (REI < 15), and 25 (54.3%) had moderate-to-severe sleep apnea (REI ≥ 15). Alcohol use and higher body mass index (BMI) were significantly associated with moderate-to-severe apnea (p = 0.01 for both). The BQ demonstrated a sensitivity of 45.8%, specificity of 72.7%, PPV of 64.7%, and NPV of 55.2% for predicting moderate-to-severe sleep apnea. The mBQ improved performance to a sensitivity of 54.1%, specificity of 72.7%, PPV of 68.4%, and NPV of 59.3%. Patients with moderate-to-severe apnea exhibited significantly lower minimum oxygen saturation compared with those with no or mild apnea (p = 0.03).</p><p><strong>Conclusions: </strong>The accuracy of the Berlin Questionnaire for detecting sleep apnea in acute ischemic stroke is moderate but improves with modification of BMI weighting. Moderate-to-severe apnea is associated with lower oxygen saturation, highlighting the importance of early screening and targeted management in stroke units. Larger, multicenter studies are warranted to validate these findings and explore the prognostic implications of nocturnal hypoxemia in stroke recovery.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Varicella-zoster virus infection triggering GD3 antibody-positive variant Guillain-Barré syndrome: a case report and literature review.","authors":"Yujun Wu, Liyan Gu, Jieyi Liu, Weihua Yan, Jie Wei","doi":"10.1186/s12883-026-04938-x","DOIUrl":"https://doi.org/10.1186/s12883-026-04938-x","url":null,"abstract":"<p><strong>Background: </strong>Bilateral facial palsy variant Guillain-Barré syndrome (GBS) is a distinct clinical subtype. As an acute immune-mediated polyradiculoneuropathy often triggered by infections, varicella-zoster virus (VZV) is a rare yet significant precipitating factor for this variant. Anti-ganglioside antibodies, particularly anti-GD3, are involved in the pathogenesis of GBS, but their significance in VZV-associated bilateral facial palsy subtype remains incompletely elucidated.</p><p><strong>Case presentation: </strong>We report a 46-year-old female who developed acute bilateral facial palsy and limb sensory deficits following VZV infection. Serum anti-ganglioside testing confirmed GD3 IgG positivity, and cerebrospinal fluid analysis revealed albuminocytological dissociation. Nerve conduction studies supported a demyelinating polyneuropathy, and the patient showed significant improvement after intravenous immunoglobulin therapy.</p><p><strong>Conclusions: </strong>This case suggests that VZV may act as a potential trigger for GD3 antibody-positive variant GBS. Early immunotherapy may improve outcomes, emphasizing the need for systematic antibody testing in atypical presentations of this variant GBS. Further studies are required to clarify the pathophysiological role of GD3 antibodies in VZV-associated variant GBS.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term cerebral atrophy and cognitive function in patients recovering from progressive multifocal leukoencephalopathy: two case reports.","authors":"Sunao Takahashi, Daisuke Ono, Takanori Yokota, Nobuo Sanjo","doi":"10.1186/s12883-026-04949-8","DOIUrl":"https://doi.org/10.1186/s12883-026-04949-8","url":null,"abstract":"<p><strong>Background: </strong>Long-term brain atrophy and cognitive function have rarely been reported in patients without pre-existing brain disorders who survived progressive multifocal leukoencephalopathy (PML).</p><p><strong>Case presentation: </strong>Patient 1 was a 38-year-old woman with late-onset combined immunodeficiency, who presented with progressive cognitive decline and right hemiparesis. Brain MRI revealed a hyperintense lesion in the left frontal lobe. Patient 2 was a 53-year-old man in remission from follicular lymphoma, who experienced cognitive deterioration and displayed hyperintense signals in the left frontal and bilateral posterior lobes on MRI. Brain biopsy confirmed PML in both patients. After recovering from acute neurological decline, the cognitive and physical function of the patients was followed and we retrospectively analyzed sequential alterations in the MRI over eight years. Hyperintense lesion areas, cerebral hemisphere size, and intracranial volume were measured to calculate the monthly change ratios of the brain (MCRB), along with assessment of the third ventricle width. Both patients experienced no relapse. Wechsler Memory Scale-Revised scores improved in Patient 1 but slightly declined in Patient 2 despite stable Mini-Mental State Examination scores in both patients. MRI results were classified as lesion expansion, lesion reduction, and chronic atrophy. During the chronic atrophic stage, MCRB decreased by 0.06% and 0.09% in Patients 1 and 2, respectively. The third ventricle widened by 3 and 25 μm/month in Patients 1 and 2, respectively.</p><p><strong>Conclusion: </strong>Progressive cerebral atrophy occurs during PML's chronic stage, even without relapse. In these two cases, the patient with extensive bilateral lesions in the acute phase showed greater third ventricle enlargement and cognitive decline.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of early ACTH levels on neurological recovery in patients with aneurysmal subarachnoid hemorrhage: a prospective cohort study.","authors":"Ghaith Saleh R Aljboor, Aoun Tulemat, Grace H E Tan, Nina Carlos- De Clercq, Mugurel Petrinel Rădoi, Toader Corneliu, Toma Marius Papacocea","doi":"10.1186/s12883-026-04952-z","DOIUrl":"https://doi.org/10.1186/s12883-026-04952-z","url":null,"abstract":"<p><strong>Background/objectives: </strong>Aneurysmal subarachnoid hemorrhage (aSAH) triggers a marked systemic stress response and may be accompanied by hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Adrenocorticotropic hormone (ACTH) may reflect the acute neuroendocrine response to injury and could be associated with early functional status. This study aimed to describe the frequency of acute-phase ACTH abnormalities and evaluate the association between early ACTH levels and functional outcomes at hospital discharge in patients with aSAH.</p><p><strong>Methods: </strong>In this prospective cohort study, 20 consecutive aSAH patients admitted within 48 hours of symptom onset were enrolled. Plasma ACTH levels were obtained at random time points within the first 48 hours of admission (predefined cutoff ≤7 days; no patient exceeded 48 hours), prior to definitive aneurysm treatment. Blood samples were obtained within 24 hours of admission and prior to surgical intervention. Sampling was targeted between 08:00 and 10:00 to minimize circadian variation; however, minor deviations were unavoidable in the acute neurocritical care setting. Functional outcomes were assessed at discharge using the Glasgow Outcome Score (GOS) and Modified Rankin Scale (MRS). Associations were evaluated using Spearman correlation, non-parametric group comparisons, and exploratory multivariable regression analyses adjusting for key severity variables.</p><p><strong>Results: </strong>Using institutional laboratory reference ranges, 12/20 patients (60%) had ACTH values below the reference range, 7/20 (35%) were within range, and 1/20 (5%) had elevated ACTH. ACTH levels were significantly associated with discharge outcomes (mRS: ρ = +0.67, p = 0.0014; GOS: ρ = -0.59, p = 0.0063). ACTH distributions differed between favourable (mRS ≤ 2) and unfavourable (mRS > 2) outcome groups (p = 0.014). In exploratory multivariable analysis, ACTH showed a consistent association with outcome but did not remain statistically significant after adjustment.</p><p><strong>Conclusions: </strong>Early ACTH levels obtained during the acute hospitalization were associated with short-term functional outcomes at discharge after aSAH. Given the random sampling design, the stress-sensitive nature of ACTH, and the absence of paired cortisol measurements, these findings should be interpreted as reflecting ACTH dysregulation rather than definitive endocrine deficiency. Larger studies with standardized sampling and longer-term follow-up are warranted.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic recovery of piriform cortex function and its impact on cognitive processing speed following mild COVID-19.","authors":"Hyeonseok Jeong, Youngeun Shim, Yoonji Joo, Yejin Kim, Chaewon Suh, Yunjung Jin, Harin Song, In Kyoon Lyoo, Sujung Yoon","doi":"10.1186/s12883-026-04943-0","DOIUrl":"https://doi.org/10.1186/s12883-026-04943-0","url":null,"abstract":"<p><strong>Background: </strong>Although the neurological sequelae of severe COVID-19 are increasingly recognized, the long-term neural impact of uncomplicated mild SARS-CoV-2 infection remains insufficiently characterized. This study investigated post-infection alterations in piriform cortex activity, a region central to olfactory processing and integrative cognitive-emotional networks, and their associations with cognitive outcomes in adults.</p><p><strong>Methods: </strong>Fifty adults with pre- and post-SARS-CoV-2 magnetic resonance imaging (MRI) and clinical/neuropsychological data were analyzed. A demographically matched control group of 50 individuals without prior COVID-19 or vaccination was included. Resting-state functional MRI assessed amplitude of low-frequency fluctuations (ALFF) within the piriform cortex as an index of regional neural activity.</p><p><strong>Results: </strong>Baseline piriform ALFF did not differ between the two groups (p = 0.421). Following infection, piriform ALFF exhibited a significant quadratic trajectory (p = 0.003), characterized by early elevation relative to baseline, a decline to a nadir at approximately three months, and subsequent recovery toward baseline levels by six months. Greater acute COVID-19 symptom burden correlated with higher piriform ALFF (β = 0.34, p = 0.017). Elevated ALFF was associated with reduced processing speed (β = -0.52, p = 0.001). Mediation analysis demonstrated that piriform ALFF significantly mediated the relationship between symptom burden and processing speed (indirect effect b = -0.081, p = 0.037).</p><p><strong>Conclusions: </strong>Piriform cortex function demonstrated a dynamic, nonlinear pattern within six months after mild COVID-19, marked by early hyperactivity, later downregulation, and gradual normalization. Altered piriform activity mediated the association between symptom burden and processing speed deficits, suggesting transient post-infection neurophysiological disruption with potential relevance to cognitive symptoms. Longitudinal follow-up is warranted to clarify underlying mechanisms and long-term implications.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galeal scoring for salvage scalp closure following cranioplasty failure: a case report.","authors":"Musawer Khan, Waseem Sajjad, Sajid Khan, Naeem Ul Haq, Shehzad Sadbar","doi":"10.1186/s12883-026-04905-6","DOIUrl":"https://doi.org/10.1186/s12883-026-04905-6","url":null,"abstract":"<p><strong>Introduction: </strong>Achieving tension-free scalp closure after decompressive craniectomy or cranioplasty can be quite demanding, especially in patients who have developed fibrosis or infection from previous procedures. In such situations, galeal scoring (galeotomies) can improve scalp mobility. Although this technique is well known in plastic surgery, it is not commonly reported in neurosurgical work.</p><p><strong>Case presentation: </strong>A 30-year-old man sustained a high-velocity head injury that produced a large right fronto-parietal acute subdural hematoma with marked midline shift. He underwent an emergency decompressive craniectomy, leaving the bone flap off. After recovery, a delayed cranioplasty was performed using a custom implant, but the wound later became infected, requiring removal of the prosthesis and repeated debridement. As a result, the scalp contracted, and primary closure became difficult. During the final reconstruction, several small galeal-relaxing cuts were made to relieve tension and allow a comfortable closure.</p><p><strong>Outcome: </strong>The wound healed completely without further infection. At six months, the patient remained neurologically stable with a satisfactory cosmetic appearance.</p><p><strong>Conclusion: </strong>Galeal scoring offers a simple, inexpensive, and safe way to gain additional scalp mobility when closure is tight. It can often prevent the need for complex flap or graft procedures and is worth considering in similar neurosurgical cases.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of CD36 deficiency with multiple white matter lesions.","authors":"Yuta Kizuka, Hiroyuki Yamakawa, Yu Iwabuchi, Jun Sakai, Chika Terayama, Yoko Yatabe, Tomoko Arai, Hiromichi Matsushita, Masaki Ieda, Jin Nakahara, Yoshikane Izawa","doi":"10.1186/s12883-026-04945-y","DOIUrl":"https://doi.org/10.1186/s12883-026-04945-y","url":null,"abstract":"<p><strong>Background: </strong>CD36 deficiency is associated with abnormal fatty acid metabolism, which may increase the risk of developing atherosclerosis. However, there are few reports on a possible link between CD36 deficiency and cerebral white matter lesions.</p><p><strong>Case report: </strong>We present the case of a 44-year-old woman with heart failure due to CD36 deficiency and multiple white matter lesions. Her comprehensive examination for heart failure, including a single-photon emission computed tomography (SPECT) with ²⁰¹thallium and ¹²³I-β-methyl-p-iodophenyl pentadecanoic acid, revealed a fatty acid metabolism disorder in the myocardium. Flow cytometry confirmed CD36 deficiency, and a subsequent head magnetic resonance imaging (MRI) demonstrated multiple T2-hyperintense lesions in the cerebral white matter. Although the patient had hypertriglyceridemia and a history of smoking, the contribution of CD36 deficiency to the formation of white matter lesions remains unclear.</p><p><strong>Conclusion: </strong>This case suggests a potential association between CD36 deficiency and cerebral small-vessel disease. Further studies in patient cohorts with CD36 deficiency are warranted to clarify the impact of this condition on cerebral microcirculation.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare coding variation and stroke heterogeneity in Saudi Arabia: an exome‑wide association study across severity, etiology, vascular territory, and early‑onset disease.","authors":"Fahad Alkhamis, Majed M Alabdali, Abdullah S Alamri, Rudaynah Alali, Alawi H Habara, Mohammed S Akhtar, Shahad F Alkhamis, Mercy Rophina, Abdullah M Alkhudair, Chittibabu Vatte, Brendan Keating, Amein K Al-Ali","doi":"10.1186/s12883-026-04935-0","DOIUrl":"https://doi.org/10.1186/s12883-026-04935-0","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke in Saudi Arabia arises in a highly consanguineous population with a distinctive genetic architecture, likely enriching rare coding variants that influence stroke risk. Yet the contribution of these variants to stroke susceptibility, age at onset, and subtype patterns in this setting remains incompletely defined.</p><p><strong>Methods: </strong>We analyzed whole-exome sequencing data from 514 stroke patients in a case only study design. Gene-based rare variant burden analyses was performed using SAIGE-GENE+ burden and SKAT-O tests across predefined phenotype contrasts within the cohort, stroke severity (modified Rankin Scale, mild < 3 vs. severe ≥ 3 ,), age at onset (early-onset < 25 years vs. late-onset > 45 years; mid-life onset < 45 vs. > 45), etiological subtypes (TOAST classification), and vascular imaging patterns (intracranial vs. extracranial).Post-association functional annotations included GTEx expression, gnomAD constraint metrics, and draggability insights.</p><p><strong>Results: </strong>Gene-level associations at a suggestive threshold (p < 0.005) identified several candidates including HSP90AB1, PRR23A, and LRRC42 (severity and age-at-onset); POGZ and SMIM34 (age-at-onset); and COL9A3, DCP1B, and ADGRV1 (imaging and etiology subtypes). The highlighted genes showed varying expression across brain and vascular tissues and intolerance to loss-of-function variation. Notably, HSP90AB1, a molecular chaperone highly expressed in the brain and vasculature, has small-molecule inhibitors, supporting its potential relevance to stroke biology.</p><p><strong>Conclusions: </strong>Our findings identify exploratory candidate gene-level signals across clinically defined ischemic stroke phenotypes based on case-only within-cohort comparisons, in underrepresented population. These results should be considered hypothesis-generating and require replication and functional validation before biological or clinical inferences can be made.</p>","PeriodicalId":9170,"journal":{"name":"BMC Neurology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}