Journal of Clinical Neurology最新文献

Background and purpose: Anti-agrin antibodies (agrin Abs) have recently been identified in patients with myasthenia gravis (MG), sometimes in conjunction with antibodies (Abs) to the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), or low-density lipoprotein receptor-related protein 4. This study aimed to develop an in-house cell-based assay (CBA) for detecting agrin Abs, and to test its application to serum samples collected from individuals diagnosed with MG.

Methods: Agrin complementary DNA as cloned into a pCMV6-AC-GFP vector, which was subsequently transfected into human embryonic kidney 293T (HEK293T) cells. Transfected HEK293T cells were incubated with patient serum and antihuman immunoglobulin G Ab conjugated with a red fluorescent dye. Agrin Ab levels were measured using the CBA in 389 serum samples: 340 from patients with MG, 36 from patients with other neuromuscular diseases, and 13 from healthy controls. The presence of agrin Ab was determined based on the fluorescence intensity and colocalization using fluorescence microscopy.

Results: The expression levels of agrin mRNA and protein in transfected HEK293T cells were confirmed using the reverse-transcription polymerase chain reaction and Western blotting, respectively. Agrin expression in cells was further confirmed by immunocytochemistry. Two (0.6%) of the 340 patients with MG tested positive for agrin Ab: 1 of 191 AChR-positive patients and 1 of 54 MuSK-positive patients.

Conclusions: We have developed and validated a novel CBA for detecting agrin Abs. This CBA was successfully applied to detect agrin Abs in serum samples obtained from individuals with MG.

Background and purpose: There is a current need to understand the efficacy and quality of life (QoL) outcomes of vagus nerve stimulation (VNS). Identifying patients most likely to benefit from VNS could aid in their selection, reduce side effects, and improve outcomes. Here we studied clinical and QoL outcomes after VNS in patients with drug-resistant epilepsy and attempted to identify response predictors.

Methods: This was a retrospective study of 55 patients with drug-resistant epilepsy treated surgically during 2004-2018, 40 of whom were eligible for inclusion in the analysis. All surgeries were performed using a standard protocol by a neurosurgeon experienced in epilepsy treatment after referral by an attending neurologist. Data were collected from medical records and through a 28-item questionnaire on seizure frequency, duration, and strength before and after VNS, as were the number and type of postoperative complications and their significance to the patient, and QoL based on the 31-item Quality of Life in Epilepsy questionnaire.

Results: Improvements in seizure frequency, duration, and strength were observed in 65% of the patients with drug-resistant epilepsy treated using VNS. The most common complication was hoarseness (70%), and complications were poorly tolerated by 12% of the patients. Repeated surgery to replace batteries or electrodes was required in 20% of the patients. Health status was the only QoL parameter significantly impacted by VNS. No significant efficacy predictors were identified.

Conclusions: Efficacy across the first month of treatment is a strong indicator of long-term outcomes of VNS. The stimulator can be removed if it does not provide any benefit.

Background and purpose: Essential tremor with a midline distribution (Mid-ET) may represent a distinct subtype of essential tremor (ET) that primarily affects midline structures, often indicating advanced disease stage and increased severity. Recent studies have highlighted the complexity of Mid-ET, but research on neurological soft signs (NSS) in Mid-ET remains insufficient.

Methods: The patients with ET included in this cross-sectional study were divided into two subgroups based on whether or not the ET had a midline distribution: Mid-ET and No-Mid-ET. Comparative analyses were performed to assess clinical features and NSS prevalence in these subgroups.

Results: Among 1,160 patients, 567 (48.9%) were Mid-ET and 593 (51.1%) were No-Mid-ET. The prevalence rates of head, face (including the jaw), and voice tremors were 31.9%, 23.0%, and 25.8%, respectively. In Mid-ET, tremor often affects multiple midline structures simultaneously. In the entire cohort, 24.7%, 16.6%, and 7.6% of patients exhibited tremors in one, two, and three midline structures, respectively. The prevalence of common NSS, including mild cognitive impairment, impaired tandem gait, and questionable dystonic posturing, was significantly higher in the Mid-ET than the No-Mid-ET subgroup (all p<0.001). Furthermore, we found that female sex (p<0.001), olfactory dysfunction (p=0.003), and questionable dystonic posturing (p=0.004) were associated with Mid-ET.

Conclusions: Mid-ET and No-Mid-ET presented significant clinical differences. The presence of questionable dystonic posturing may contribute to the distinct characteristics of Mid-ET, suggesting the presence of pathophysiological differences between the subgroups. Further investigations are warranted to determine the potential pathophysiological link between NSS and Mid-ET.

Background and purpose: Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation.

Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months.

Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15-87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse. Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections.

Conclusions: This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background and purpose: The risk factors for developing epilepsy following febrile convulsion (FC) have been studied extensively, but the underlying genetic components remain largely unexplored. Our objective here was to identify the risk loci related to FC through a genome-wide association study of Korean epilepsy patients.

Methods: We examined associations between a history of FC and single-nucleotide polymorphisms (SNPs) in data obtained from 125 patients with focal epilepsy: 28 with an FC history and 97 without an FC history.

Results: Among 288,394 SNPs, 5 candidate SNPs showed p<1×10⁻⁴. Regional association plots of these SNPs identified a novel locus adjacent to PROX1 that is implicated in hippocampal neurogenesis and epileptogenesis. The allele frequencies of the SNPs upstream of PROX1 including two candidate SNPs (rs1159179 and rs7554295 on chromosome 1) differed significantly between the groups with and without an FC history. In contrast, the allele frequencies of the SNPs inside PROX1 showed no differences, indicating dysregulated expression of PROX1 rather than a functional alteration in the PROX1 protein.

Conclusions: This novel discovery of SNPs upstream of PROX1 suggests that the dysregulated expression of PROX1 contributes to the development of focal epilepsy following FC. We propose that these SNPs are potential genetic markers for focal epilepsy following FC, and that PROX1 represents a potential therapeutic target of antiseizure medications.

Background and purpose: Neurocysticercosis is a parasitic infection caused by Taenia solium larvae that leads to various neurological symptoms, including vision loss. This systematic review analyzed cases of vision loss associated with neurocysticercosis to assess its etiology and vision outcomes.

Methods: Following PRISMA guidelines, the review included reports on human subjects with vision loss due to neurocysticercosis and is registered with PROSPERO (CRD42024556278). The PubMed, Scopus, Embase, and Google Scholar databases were searched.

Results: This review included 149 records from 176 patients with a mean age of 27.5 years, comprising 40.3% females, 59.1% males, and 0.6% subjects of unknown sex. Most cases were from Asia, predominantly India. The illness duration varied, but was mostly between 1 and 6 months. In addition to vision loss, common symptoms were headache or orbital pain (30.7%), seizures (12.5%), and altered consciousness (5.7%). Vision loss was mainly unilateral (72.7%). Imaging abnormalities included multiple cystic brain lesions (16.5%), enhanced lesions (4.0%), and calcified lesions (2.3%). Intravitreal and retinal regions were most affected (52.3%), followed by the anterior chamber (6.2%), orbital apex (5.1%), and optic nerve (6.2%). Anticysticercal drugs were the primary treatment, with 57.4% of cases showing improvement. Surgical excision was performed in 40.9% of cases with intravitreal or retinal cysts.

Conclusions: Vision loss in neurocysticercosis is mainly due to intravitreal and retinal involvement, and is frequently associated with multiple cystic brain lesions. Anticysticercal drugs can produce improvements, though surgical intervention is often needed for intravitreal or retinal cysts. Most of the patients in this review improved, though severe outcomes such as eye loss were reported.