OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation. METHODS: A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-12). RESULTS: A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic. CONCLUSION The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.
Humans ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Male ; Female ; Asian People/genetics* ; Adult ; Haplotypes ; Membrane Proteins/genetics* ; Exome Sequencing ; GTP-Binding Proteins/genetics* ; Mutation ; Middle Aged ; China ; Genetic Association Studies ; East Asian People

Intraoperative hemorrhage is a life-threatening complication during neurosurgery, especially in posterior fossa surgery, where critical vasculature and brain structures are present. Adenosine has been used in neurovascular surgery, particularly in the management of intraoperative aneurysm rupture and hemorrhage for its ability to produce transient flow arrest. This case report describes a novel application for adenosine, in which adenosine-induced flow arrest was used to facilitate control of a vascular injury sustained during meningioma surgery.

A 46-year-old female diagnosed with a petroclival meningioma after presenting with a several-month history of headache, dizziness, and loss of balance underwent craniotomy and excision of the meningioma. The patient received general endotracheal anesthesia, and was maintained on remifentanil, propofol, and low-dose sevoflurane. During posterior excision of the meningioma, the basilar artery was inadvertently lacerated, resulting in significant blood loss. Adenosine was given through a subclavian catheter, and produced severe bradycardia, hypotension, then asystole for approximately 50 seconds. Adenosine-induced flow arrest allowed for initial control of the vascular injury through coagulation, while further hemostasis was achieved through hemostatic agents and muscle tamponade.

This case report demonstrates the usefulness of adenosine-induced flow arrest in the management of intraoperative hemorrhage from an intracranial vascular injury. Adenosine-induced flow arrest has documented safety and efficacy in other neurosurgical applications. As the management of intraoperative hemorrhage is an essential component of neuroanesthesia, this technique may be considered in similar circumstances of major vascular injury to facilitate hemostasis.

BACKGROUND

Spinocerebellar Ataxia (SCA) represents a rare and heterogeneous group of neurodegenerative disorders, typically characterized by the progressive loss of coordination of movement, resulting primarily from cerebellar dysfunction. This case report discusses the history, clinical presentation, and diagnostic findings of a patient who exhibited symptoms suggestive of SCA. Given the notable familial pattern, further evaluation was undertaken using genetic testing. The objective of this paper is to present the clinical, genetic findings, and inheritance pattern of a patient and her family with SCA.

Our case is a 36-year-old Filipino female with progressive cerebellar dysfunction for over a decade. Cranial Magnetic Resonance Imaging (MRI) revealed bilateral cerebellar atrophy. Genetic testing identified a Variant of Uncertain Significance (VUS) in the inositol 1,4,5- triphosphate receptor type 1 (ITPR1) gene, a finding consistent with Spinocerebellar Ataxia type 15 (SCA 15). This represents the first reported case of SCA 15 in the Philippines and in Asia.

A detailed pedigree assessment revealed that 18 immediate and extended family members had similar symptoms suggestive of hereditary ataxia. Ten relatives had already passed away, and four could not be contacted for further evaluation. Three available family members were examined and likewise demonstrated comparable cerebellar findings, supporting a familial pattern of the disease.

The findings from this case series suggest that SCA 15 may be present in Filipino families, with an autosomal dominant (AD) inheritance pattern. While no data on the prevalence or incidence of SCA15 in the Philippines currently exists, this report calls attention to the need for further research and genetic studies within the Filipino population.

Introduction: Electrolyte imbalance is common in central nervous system infections. Arginine vasopressin deficiency (AVP-D), Cerebral Salt Wasting (CSW), and Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) are important etiologies that can cause opposing extremes of serum sodium, posing diagnostic and therapeutic challenges. We report a rare case of transient central AVP-D followed by CSW secondary to tuberculous meningitis (TBM). Case: An 18-year-old female presented with a 1-month history of fever, reduced responsiveness, and visual hallucinations. Her Glasgow Coma Scale was E4V1M4 with neck stiffness and upper motor neuron signs. Initial investigations revealed severe hyponatremia (119 mmol/L) and communicating hydrocephalus with third ventricle ballooning on brain imaging. Coupled with a positive tuberculosis contact, anti-tuberculous therapy was initiated for probable TBM alongside 3% saline correction prior to insertion of external ventricular drain (EVD). Her condition deteriorated on day 5, requiring intubation for aspiration pneumonia. Repeated imaging showed worsening hydrocephalus, necessitating EVD revision. She subsequently developed polyuria (urine output [UO] 150–300 mLs/hour), with biochemical findings consistent with AVP-D (serum sodium 154 mmol/L; urine osmolality 96 mOsm/kg; urine sodium <20 mmol/L). Intravenous desmopressin 1 mcg was administered, and UO reduced to 30 mLs/hour. However, polyuria recurred on Day 9, accompanied by tachycardia, hypotension, and a rapid decline in serum sodium to 120 mmol/L. Diagnosis of CSW was established (urine sodium 204 mmol/L; urine osmolality 470 mOsm/kg). Oral fludrocortisone was initiated and titrated to 0.4 mg daily to maintain serum sodium >130 mmol/L. Due to persistent hydrocephalus, right ventriculoperitoneal shunt was inserted on Day 22, after which her UO gradually decreased, allowing tapering of fludrocortisone. She remains on fludrocortisone 0.1 mg daily with ongoing rehabilitation. Conclusion TBM can be complicated by SIADH, AVP-D, or CSW. Concurrent AVP-D and CSW have not been reported. This case highlights the dynamic electrolyte disturbances in TBM which may lead to diagnostic confusion and therapeutic error. Early recognition and tailored therapy, alongside definitive management to reduce intracranial pressure, are essential for optimal outcomes.
Hypernatremia ; Hyponatremia ; Tuberculosis, Meningeal

BACKGROUND : The prevalence of autonomic nervous system disorders is increasing due to the complications of chronic illnesses that become more severe with age. The Composite Autonomic Symptom Score-31 (COMPASS-31) is a questionnaire that assesses autonomic function and has been utilized globally. This study aimed to conduct cultural adaptation and validation of the COMPASS-31 in Indonesia, particularly for the elderly. METHODS : This cross-sectional study involved elderly individuals aged 60 years and older. The process included translation, cultural adaptation, back-translation, and reliability tests. The COMPASS-31 questionnaire was translated from English to Indonesian by a certified translator, a native Indonesian speaker without medical background. A panel of experts comprising a neurologist, a gerontologist, and a physiologist discussed the translated questionnaire and made cultural adaptations. Facial and content validity tests were conducted on 11 elderly individuals. The inputs for revision are discussed by the expert panel. The questionnaire was then back-translated into English by a native English speaker, professional translator, without a medical background. The questionnaire was checked for reliability in 52 elderly subjects. Reliability testing was conducted separately for the binomial and polynomial questions of the COMPASS-31 questionnaire. RESULTS : The reliability test yielded a Cronbach’s alpha of 0.729 for the binomial questions and 0.722 for the polynomial questions, indicating high reliability. CONCLUSIONS The Indonesian version of COMPASS-31 questionnaire is a valid and reliable symptom assessment tool for use in the elderly.
aging ; autonomic disorders ; autonomic nervous system diseases ; surveys and questionnaires

BACKGROUND AND OBJECTIVE

Meningiomas represent the most prevalent benign intracranial tumors, comprising 13- 26% of primary intracranial neoplasms. These tumors derive their blood supply from both extracranial and intracranial circulation. Over recent decades, pre-operative embolization (POE) has emerged as a potential adjunctive therapy to surgery, aiming to reduce tumor vascularity. Our study seeks to explore the potential correlation between the extent of devascularization following POE of meningiomas and intraoperative blood loss.

This cross-sectional study involved nine meningioma patients at a tertiary hospital, involving chart review of patients across four years. These patients were referred for POE due to angiographic evidence of a hypervascular mass between January 2018 and January 2022. We collected demographic data, tumor characteristics (including location, size, and vascular supply), and intraoperative variables such as total operative time and blood loss. Statistical analyses aimed to uncover correlations between vascularization degree and various factors.

Our population consists predominantly of females (53.68%), with a mean age of 45.85 ± 13.65 years. Only one mortality was recorded (7.7%). Pre-operative embolization achieved devascularization in the majority (69.2%) of cases, with approximately two-thirds (66.7%) experiencing complete devascularization. Mean total operative time stood at 336.11 ± 301.88 minutes, with a mean post-operative blood loss of 985.56 ± 1013.72 milliliters. Additionally, for those with recorded recovery times, the mean recovery time was 14.32 ± 13.51 hours.

Mortality rates showed no association with sex, devascularization status, or number of feeding vessel zones. Furthermore, the extent of devascularization did not correlate with age, sex, number of feeding vessel zones, postoperative blood loss, total operative time, or recovery time (p >0.05).

In summary, this study represents a significant endeavor to elucidate factors influencing meningioma outcomes following pre-operative embolization. Despite limitations regarding patient numbers, our study offers valuable insights into operative parameters and embolization considerations for future analyses in our tertiary center.

INTRODUCTION

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited condition seen in one of 4000 live births, predisposing to peripheral and central neurofibromas. Spinal tumors are seen in 40% of cases with NF1 and only 2% will develop symptoms, and among those who develop symptoms where 33% showed intradural extramedullary location. Thoracic spinal dumbbell neurofibroma is even rarer, and cases that extend to obliterate the posterior mediastinum even more so, with the case presented being the largest in size documented to date.

A 34-year-old female presented since childhood clinical findings consistent with Neurofibromatosis Type I: generalized cafe-au-lait macules, axillary freckling, cutaneous neurofibromas, two iris Lisch nodules identified via slit lamp examination, and anterolateral bowing of the right tibia, and no known parental history of Neurofibromatosis Type I. Prior to admission, the patient presented with progressive loss of motor strength of the lower extremities, and progressive dyspnea. Work-up revealed a Thoracic Intradural Extramedullary Neurofibroma extending to the Right Posterior Mediastinum measuring 15.3 cm x 12.9 cm x 9.7 cm in the thoracic cavity compressing the right lung and bronchus. An extensive two stage surgery was contemplated involving an initial resection of the Intradural mass, with spine instrumentation for support, and subsequent resection of the mediastinal extension. However, complications from the compressing tumor: complete cord transection syndrome causing spinal autonomic dysfunction, lung and airway compromise causing prolonged intubation and difficulty in weaning from mechanical ventilatory support, extensive thrombus formation in the right jugular vein, and nosocomial infections all created compounding difficulties for the surgical technique and anesthetic plan.

Cornerstone management for dumbbell spinal neurofibromas involves their total removal. The best results are obtained in patients showing minimal neurological deficits during the preoperative period. However, little improvement may be expected from patients who develop complete transection syndrome during the postoperative period. Concurrent medical management to prepare the patients are equally important. The multi-subspecialty approach required in managing these cases entails a good balance between the disability before the surgery, anticipated outcomes, and quality of life of the patients.

Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans ; Biomarkers/cerebrospinal fluid* ; Nervous System Diseases/diagnosis* ; Brain Injuries/metabolism* ; Phosphopyruvate Hydratase/cerebrospinal fluid* ; Glial Fibrillary Acidic Protein/blood* ; S100 Calcium Binding Protein beta Subunit/blood* ; tau Proteins/cerebrospinal fluid* ; Ubiquitin Thiolesterase/blood* ; Myelin Basic Protein/cerebrospinal fluid* ; Neurofilament Proteins/blood* ; MicroRNAs/blood* ; Brain Injuries, Traumatic/metabolism*

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*