Allgrove syndrome, also known as Triple-A syndrome, is a rare autosomal recessive disorder characterized by the triad of alacrima, achalasia, and adrenal insufficiency, alongside a broad spectrum of neurological and autonomic dysfunctions. We present a compound heterozygosity for the pathogenic NM_015665.6:c.787T > C, p.(Ser263Pro) and the not previously described in the literature NM_015665.6:c.1442 A > G, p.(His481Arg), as a possible cause for Allgrove syndrome. Exome sequencing was performed in a female patient with achalasia, alacrima, optic atrophy, asymmetrical axonal sensorimotor polyneuropathy, segmental demyelination, and chronic denervation, revealing the above-mentioned compound heterozygosity. Segregation analysis was performed in three siblings of the proband and in the mother. The affected brother of the proband (presenting with achalasia, alacrimia, motor neuropathy, autonomic dysfunction, optic atrophy and osteoporosis), was found to be compound heterozygotes for the same variants. Although the paternal genotype was not available, the absence of the p.(His481Arg) variant in the mother indicates paternal inheritance of this variant, providing indirect evidence that the two AAAS variants are located on different alleles (in trans). The proband and her affected sibling were found to carry compound heterozygosity for the known pathogenic AAAS variant p.(Ser263Pro) and the novel p.(His481Arg) variant. Segregation analysis in available family members supports a contributory role of p.(His481Arg) in the context of autosomal recessive inheritance, however, phase could not be directly confirmed due to the unavailability of the paternal sample. Functional validation and/or identification of the variant in unrelated affected individuals would be required to further clarify its pathogenic significance. We also provide a comprehensive review of reported Allgrove syndrome cases in the literature carrying compound heterozygosity for the NM_015665.6:c.787T > C, p.(Ser263Pro) variant and the respective wide spectrum of this syndrome.

Giant cell arteritis is relatively rare in Indian subjects. A retrospective chart review of cases of giant cell arteritis (GCA) in patients with anterior ischemic optic neuropathy (AION) for last five years (2015 to 2020) in a tertiary care Institution was done. GCA cases were diagnosed on the basis of clinical criteria of new onset of headache along with marked sudden visual loss supplemented by raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and confirmed on temporal artery biopsy. Occult GCA was defined as patients presenting with predominantly ophthalmic symptoms without systemic involvement. All the clinical details of GCA cases have been described in detail. Out of 30 cases of AION, GCA was the diagnosis in 4 cases (13.33%). Among the 4 cases of GCA, 3 cases (75%) were of occult in nature. Three cases underwent superficial temporal artery biopsy which was confirmatory for GCA. GCA was rare in Indian scenario. Earlier age of presentation, male preponderance, and higher number of occult GCA with predominantly ophthalmic involvement were the findings in our study.

Craniometaphyseal dysplasia (CMD) is characterized by metaphyseal dysplasia, sclerosis of the skull base, and craniofacial bone overgrowth. The autosomal dominant form of CMD (OMIM: 123000) is associated with features such as mandibular prognathism, dental misalignment, and bony paranasal bossing. In contrast, the autosomal recessive form (OMIM: 218400) can result in severe distortion of the craniofacial structure, accompanied by complications such as cranial nerve compression, facial palsy, deafness, and visual impairment. Mutations causing CMD have been linked to the ANKH gene sequence variants. This case report describes a 11-year-old male diagnosed with CMD based on clinical and genetic findings. The patient presented with facial asymmetry, mandibular prognathism, delayed intellectual response, and gradual visual impairment, culminating in optic nerve compression and partial blindness. Radiographic evaluation revealed mixed dentition, thickened skull bones, cranial suture fusion, and Chiari I malformation. Biochemical analysis indicated hyperdense bone with normal serum calcium and phosphorus levels. Genetic testing confirmed an autosomal dominant pathogenic variant of a heterozygous nonframeshift deletion mutation of the ANKH gene (c.1124_1126del, p.Ser375del).

Sagittal split ramus osteotomy (SSRO) is the most commonly performed mandibular procedure in orthognathic surgery. Although generally safe, neurosensory disturbance (NSD) of the inferior alveolar nerve (IAN) remains a frequent complication that can impair oral function and quality of life. This retrospective study included 463 patients who underwent SSRO, comprising 873 rami, at our department between 2014 and 2024. Patient- and ramus-level variables were extracted from electronic medical records, with postoperative NSD of the IAN defined as the primary outcome. We investigated the presence or absence of mandibular canal (MC)-lateral cortical bone (LCB) contact on preoperative computed tomography, as well as the three types of lateral osteotomy line on postoperative panoramic radiographs. Descriptive statistics were used to summarize clinical characteristics, and the incidence of NSD was evaluated. Trends in annual NSD proportions were analyzed using a Cochran-Armitage trend test, and univariable and multivariable logistic regression analyses were performed to assess associated factors. The incidence of NSD was 5.6% at the patient-level and 4.0% at the ramus-level. A decreasing trend in annual NSD incidence was observed (p < 0.001). In multivariable analysis, the presence of MC-LCB contact was strongly associated with NSD (odds ratio, 4.96; 95% confidence interval, 2.41-10.06; p < 0.001). The incidence of NSD after SSRO was approximately 5% and showed a declining annual trend over time, possibly reflecting increasing surgical experience and improved instrumentation. MC-LCB contact was associated with an approximately fivefold higher risk of NSD, highlighting the importance of careful and gentle osteotomy.

Unilateral vocal fold paralysis secondary to peripheral nerve injury presents limited treatment options and inconsistent outcomes. This protocol describes an electroacupuncture-based cerebral electric field therapy designed to target neuroanatomically relevant pathways through combined scalp, posterior cervical, and anterior neck electroacupuncture. The procedure includes standardized point selection, stimulation parameters, and treatment sequencing, followed by objective functional assessment using laryngoscopy and videofluoroscopic swallowing study. In a representative case, the application of this protocol was associated with observable improvements in voice quality and swallowing function. Patients with unilateral vocal fold paralysis frequently experience hoarseness, dysphagia, aspiration, and reduced laryngeal sensation, leading to substantial functional limitations and decreased quality of life. This protocol demonstrates the feasibility of electroacupuncture-based cerebral electric field therapy as a structured intervention for unilateral vocal fold paralysis and provides a reproducible framework for future clinical exploration. Additional investigation may help clarify its potential role as a supportive therapeutic option. Future controlled studies may further evaluate its clinical effectiveness and applicability.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune CNS disease that frequently causes severe optic neuritis, yet the molecular mechanisms driving retinal damage remain incompletely understood, especially across different NMOSD subgroups. Müller glial cells, which maintain retinal water-ion homeostasis through AQP4 and Kir4.1 channels, may represent a primary retinal target of circulating NMOSD-related autoantibodies and serum factors. We investigated how sera from AQP4-IgG+, MOG-IgG+, and double-seronegative (DSN) NMOSD patients affect the expression and localization of key Müller cell biomarkers. Human MIO-M1 Müller cells were stimulated with complement-inactivated patient or healthy control sera, and protein/mRNA levels of AQP4, Kir4.1, CRALBP, VEGF, and IL-6 were evaluated using immunofluorescence, Western blotting, and RT-qPCR. AQP4 membrane localization and internalization were assessed using WGA and EEA1 colocalization analyses. AQP4-IgG+ sera uniquely induced a marked reduction in AQP4 and Kir4.1 protein expression, together with mild AQP4 internalization and reduced membrane association. Despite protein loss, AQP4 and Kir4.1 transcripts were significantly upregulated, indicating a compensatory transcriptional response to antibody-mediated depletion. MOG-IgG + sera produced no major changes in the examined markers. In contrast, DSN sera selectively increased VEGF expression at both protein and mRNA levels, suggesting an alternative, antibody-independent mechanism of Müller cell activation. IL-6 expression showed non-significant changes across groups. These findings demonstrate subgroup-specific retinal glial responses to patient sera, with AQP4-IgG mediating early complement-independent loss of the AQP4-Kir4.1 water-ion channel complex, and DSN sera engaging distinct VEGF-related pathways. Our study establishes Müller cells as active contributors to NMOSD-associated retinal pathology and provides a foundation for exploring subgroup-tailored changes.

Neuromyelitis optica spectrum disorder (NMOSD) constitutes a demyelinating condition of the central nervous system driven by autoimmune inflammation. A hallmark of its pathogenesis is the antibody-mediated injury of astrocytes, primarily targeting the water channel aquaporin-4 (AQP4). Animal models are indispensable for dissecting disease mechanisms and accelerating the development of new therapies. However, creating models that closely mirror NMOSD remains difficult, in part because immune tolerance limits the induction of the autoreactive responses central to the disease. This review follows NMOSD over time and surveys experimental systems across four interconnected mechanistic themes: breakdown of immune tolerance, T-B cell collaboration, antibody-mediated effector injury, and the formation of pro-inflammatory tissue milieus that sustain pathology. For each theme, we outline the rationale for model design, evaluate how well key pathological features are produced, and discuss the limitations that shape interpretation. Rather than offering a single continuous reconstruction of human NMOSD, these platforms capture complementary and only partially overlapping aspects of pathogenesis. Taken together, they provide a mechanism-oriented framework for understanding how upstream immune dysregulation, humoral immunity, and tissue-level permissive factors shape disease expression. At the same time, they also highlight the distance between experimental systems and the heterogeneous, dynamic course seen in patients. We further discuss how findings from animal studies are informing therapeutic target discovery and outline priorities for the development of next-generation models with greater translational relevance.

Background and Objectives: Visual evoked potentials (VEPs) are a simple, noninvasive method for detecting subclinical visual pathway involvement in multiple sclerosis. This study investigated the frequency of VEP abnormalities and their associations with baseline clinical, radiological, and cerebrospinal fluid (CSF) features in treatment-naïve patients with clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) without prior optic neuritis. Materials and Methods: We retrospectively reviewed newly diagnosed, treatment-naïve CIS/early RRMS patients evaluated between January 2022 and July 2024 who underwent CSF analysis. Pattern-reversal VEPs were recorded under standardized conditions. VEP abnormalities were analyzed as any or bilateral, and associations were assessed using group comparisons and multivariable logistic regression. Results: In 101 patients (mean age 31.8 ± 9.7 years; 72% female; median EDSS 1.0), latency prolongation occurred in 69 (42 any,27 bilateral) and amplitude reduction in 33 (22 any, 11 bilateral). Among patients with latency prolongation, both the number of OCB bands and the IgG index were higher (bilateral p = 0.032; any p = 0.007). In multivariable analysis, male sex (p = 0.032) and pyramidal/brainstem-onset presentation (p = 0.006) were independently associated with any amplitude reduction; neither was associated with latency abnormalities. Conclusions: VEP abnormalities are common early in the disease, even without a history of optic neuritis. Male sex and pyramidal/brainstem-onset presentation were associated with reduced amplitude, suggesting that amplitude decrease may reflect early tissue dysfunction and may be related to adverse baseline clinical features. Associations between intrathecal immune activation and prolonged latency may indicate subclinical demyelination of the visual pathways related to inflammatory activity. Larger longitudinal studies are needed to clarify the clinical significance of VEP abnormalities in early RRMS.