Neurology International

Background/Objectives: Atrophy of the thenar muscles (abductor pollicis brevis [APB], opponens pollicis [OP], and flexor pollicis brevis [FPB]) is most commonly caused by carpal tunnel syndrome (CTS). It may also occur following injury to the recurrent motor branch of the median nerve, proximal median nerve neuropathy, medial cord/lower trunk plexopathy, T1 radiculopathy, ventral horn cell disorder at C8 or T1, disuse atrophy, or congenital aplasia. Clinical observation of flattening of the thenar eminence coupled with electrodiagnostic (EDX) and ultrasound (US) studies is valuable in determining the etiology of thenar atrophy. This study describes clinical, EDX, and US findings in a large cohort of patients with thenar muscle atrophy. Methods: This is a review of 197 patients (226 hands) with thenar atrophy who underwent EDX and US studies. Patients were divided into those with total thenar atrophy (all three thenar muscles were atrophic) or partial thenar atrophy (atrophy of one or two thenar muscles) based on clinical and US findings. Results: Of the 226 hands, 174 (77.0%) had partial thenar atrophy, 217 (96.0%) had sensory loss, and all hands demonstrated weakness of the APB and OP muscles on examination. A total of 220 (97.3%) hands had EDX evidence of severe median nerve entrapment at the carpal tunnel. The compound muscle action potentials (CMAPs) of the APB muscle and sensory nerve action potentials (SNAPs) were absent in 186 (82.3%) and 212 (93.8%) hands, respectively. US study showed hyperechoic APB and OP muscles in 225 (99.6%) hands. The Heckmatt grade, determined by US, was 3 in 152 (67.3%) hands, showing increased muscle echogenicity with loss of architecture and reduced bone reflection. Conclusions: In patients with thenar muscle atrophy, EDX studies were not always conclusive for confirming CTS due to an absence of SNAP and CMAP over the APB and second lumbrical muscles. In these cases, US is important to confirm the cause of thenar atrophy.

Background: Neuromyelitis optica spectrum disorder (NMOSD) involves demyelinating astrocytopathy. Most cases have autoantibodies against aquaporin-4 (AQP4 ab), but AQP4 ab-negative patients may also meet NMOSD criteria. Overlapping clinical phenotypes of CNS inflammatory demyelinating diseases (IDDs) complicate understanding NMOSD mechanisms. Objectives: Investigate molecules related to neuroinflammation and astrocyte function as potential biomarkers of NMOSD and other IDDs by using clinical data and in vitro assays. Methods: Subjects (176) with different IDDs (NMOSD (37), MS (125), MOGAD (3), ADEM (3) and eight radiologic isolated syndromes (RIS)) were studied. Plasma concentrations of TGF-β and other cytokines were measured by single molecule array (SIMOA), Luminex and ELISA assays. Functional assays used in vitro cultured human astrocytes exposed to NMOSD subjects’ serum, followed by immunolabeling. Results: TGF-β levels were higher in NMOSD patients during attacks compared to inactive phases. AQP4+ groups in inactive phases had lower TGF-β levels than AQP4− groups. No significant difference was found for IL-1β, IL-8, IL-10, IL-17A and Thrombospondin plasma concentrations, with a minor difference for VEGF in the AQP4+ group. Astrocytes exposed to NMOSD AQP4+ and AQP4− subjects serum, with or without TGF-β1, showed no changes in C3, NFkB and HMGB1. However, the content of GLT-1 decreased in AQP4+ serum-treated astrocytes, reversed by TGF-β1. Conclusions: TGF-β may be a potential NMOSD activity biomarker, indicating different disease mechanisms based on AQP4 ab presence.

Introduction: Autoimmune encephalitis (AE) is a neurological disorder caused by immune responses targeting neuron-surface or synaptic proteins. While its immunological mechanisms have been studied, the genetic underpinnings remain unclear. This study investigates whether rare deleterious variants (RDVs) in immunological genes contribute to AE susceptibility. Method: We enrolled 36 patients with AE and 407 healthy controls without autoimmune diseases. Whole-exome sequencing was performed to identify RDVs, including start-loss, stop-gain, frameshift, splice-site variants, and deleterious missense mutations. We analyzed the distribution of RDVs in an immunological gene set and its subsets. A burden test was used to identify genes significantly associated with AE. Results: Overall, RDVs in the full immunological gene set did not differ between AE patients and controls. However, the T cell receptor signaling pathway subset showed a significantly higher RDV burden in AE patients. Within this pathway, PDK1 was significantly associated with AE. Two additional genes, CAT and MIA, also showed strong associations, although their broader gene subset, cytokines, did not display differential RDV distribution. Discussion: Our findings suggest that RDVs in specific immunological pathways, particularly the T cell receptor signaling pathway, may play a role in AE pathogenesis. The significant associations of PDK1, CAT, and MIA with AE highlight potential genetic contributors to the disease. Further functional studies are necessary to validate these associations and explore their biological relevance, potentially paving the way for improved understanding and future therapeutic targets in AE.