Association of serum Spp1 levels with disease progression in ALS and SBMA.

OBJECTIVE: In comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1). METHODS: This study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon-γ, interleukin [IL]-1ß, IL-6, IL-8, IL-10, tumor necrosis factor-α, and IL-17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels. RESULTS: In the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale-Revised (ALSFRS-R) scores (r = -0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57-72.53, p < 0.01). INTERPRETATION: Neuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.

Superior oblique palsy as the initial manifestation of anti-contactin-1 IgG4 autoimmune nodopathy: A case report.

Autoimmune nodopathy (AN) is a group of peripheral neuropathies caused by antibodies targeting the nodes of Ranvier or paranodes. It typically presents with sensory ataxia, distal limb weakness, and tremor, and often has a subacute onset, with limited response to immunoglobulin or corticosteroids. We report a case of anti-contactin-1 neuropathy initially manifesting as isolated superior oblique palsy, aiming to broaden the clinical spectrum of the disease. A 68-year-old male with well-controlled diabetes, hypertension, and hyperlipidemia developed acute binocular vertical diplopia, progressing over two months to include distal paresthesia, sensory ataxia, ageusia, and dysarthria. Concurrent nephrotic syndrome was identified. Nerve conduction studies supported demyelination. Despite treatment with intravenous methylprednisolone followed by long-term immunosuppression, some disability persisted. Serum archived during his admission tested positive for anti-contactin-1 IgG, with IgG4 as the predominant subclass, in the flow cytometry assay for AN. This case extends the clinical spectrum of AN. Some cases of isolated cranial nerve palsies, especially in the relevant context like nephrotic syndrome, may be attributed to AN. Prompt initiation of more effective therapies, such as rituximab, could significantly improve outcomes.

Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barré syndrome.

OBJECTIVE: Biomarkers are needed to predict prognosis and disease activity in patients with Guillain-Barré syndrome (GBS). The complement system is a key player in the pathogenesis of GBS. This study aimed to assess the potential utility of serum complement proteins as novel biomarkers in GBS. METHODS: We reviewed the medical records of 76 GBS patients with C3 and C4 measurements during hospitalization between 2010 and 2021. Clinical outcomes were correlated with baseline serum C3, C4, and seven additional predictors: four existing biomarkers (GM1, albumin, immunoglobulin G, neutrophil-lymphocyte ratio) and three clinical factors from the modified Erasmus GBS outcome score model. Five complement activation products (C3a, C4a, C5a, soluble C5b-9, factor Bb) were measured in 35 patients and were compared with C3 and C4 levels. Longitudinal changes in C3 and C4 levels were compared with the disease course in 12 patients. RESULTS: Higher C3, but not C4, was associated with poorer outcomes: lower Medical Research Council sum scores (MRCSS), higher GBS disability score (GBSDS), longer hospitalization, and more frequent treatment-related fluctuations. Age, MRCSS at admission, and baseline serum C3 were significant independent indicators of 1- and 3-month GBSDS. We found that C3 was positively correlated with C3a (r = 0.32) and C5a (r = 0.37), which indicates an activated complement cascade with high C3. Longitudinal change of C3 coincided with clinical severity of the disease course. INTERPRETATION: This study highlights the use of serum C3 as a novel mechanistic biomarker in GBS. Larger prospective studies are needed to validate our findings.

Skin Biopsy as a Novel Diagnostic Aid in Immune-Mediated Neuropathies.

Immune-mediated neuropathies are a heterogenous group of inflammatory peripheral nerve disorders. They can be classified according to the domain where the autoimmune process begins: the internode, paranode, or node. However, conventional diagnostic tools, electrodiagnosis (EDX), and autoantibody testing do not fully address this issue. In this institutional cohort study, we investigated the value of dermal myelinated fiber analysis for target domain-based classification. Twenty-seven consecutive patients with immune-mediated neuropathies underwent skin biopsies. The sections were stained with antibodies representative of myelinated fiber domains and were scanned using a confocal microscope. Clinical and pathological features of each patient were reviewed comprehensively. Quantitative morphometric parameters were subjected to clustering analysis, which stratified patients into 3 groups. Cluster 1 ("internodopathy") was characterized by prominent internodal disruption, intact nodes and paranodes, demyelinating EDX pattern, and absence of nodal-paranodal antibodies. Cluster 2 ("paranodopathy") was characterized by paranodal disruption and corresponding antibodies. Morphological changes were restricted to the nodes in cluster 3; we designated this cluster as "nodopathy." This report highlights the utility of skin biopsy as a diagnostic aid to gain pathogenic insight and classify patients with immune-mediated neuropathies.

Ictal Swearing as a Lateralizing Value for the Dominant Hemisphere in Temporal Lobe Epilepsy.

Ictal swearing, as an epileptic manifestation, has rarely been reported. Despite its poor localization value and unclear mechanism, several previous studies have reported that it frequently originates from the temporal lobe and more often from the non-dominant hemisphere. Herein, we report a case of a 41-year-old right-handed man with a history of stereotypical manifestation of ictal swearing with a left (dominant) hemisphere origin, confirmed by video electroencephalography monitoring. Reasonable suspicion that repetitive swearing could be a manifestation of seizures is important for clinicians not to misdiagnose the disease.

Sensory Guillain-Barre syndrome following the ChAdOx1 nCov-19 vaccine: Report of two cases and review of literature.

Massive vaccination against COVID-19 has become a global priority. Simultaneously, concerns regarding the safety of vaccines are growing. We describe two patients who developed sensory Guillain-Barre syndrome (GBS) shortly after the first dose of the ChAdOx1 vaccine. We also summarize 12 published cases of GBS after ChAdOx1 vaccination, highlighting their unique clinical and paraclinical features. We propose a possible association between the risk of GBS and the ChAdOx1 vaccine and recommend surveillance for GBS following vaccination. Population-based studies are needed to determine causality and whether specific subpopulations are susceptible.