アレキサンダー病

BACKGROUND: The relative value of nigrostriatal volumetry, quantitative T1 relaxation, and multicompartment diffusion MRI in neurodegenerative Parkinson syndromes is unclear. OBJECTIVES: To compare quantitative T1 relaxation and diffusion microstructure imaging-derived free fluid fraction (V-CSF) in the putamen and substantia nigra, together with putaminal volume, across Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and healthy controls. METHODS: We retrospectively studied 178 participants, including 59 individuals with Parkinson's disease, 30 with MSA, 60 with PSP, and 29 healthy controls assessed between 2018 and 2023. Linear models adjusted for age and sex tested group differences and associations with Hoehn and Yahr stage. RESULTS: Putaminal volume and V-CSF differed across groups (both p < 0.001), whereas putaminal quantitative T1 did not (p = 0.10). Nigral V-CSF showed broader separation than nigral quantitative T1. In multiple system atrophy, lower putaminal quantitative T1 was associated with higher Hoehn and Yahr stage (p = 0.028). CONCLUSIONS: Diffusion-derived free fluid and volumetry captured neurodegeneration more consistently than quantitative T1.

BACKGROUND: Myeloperoxidase (MPO), a heme-containing enzyme released by activated polymorphonuclear neutrophils (PMNs) represents a key mediator of inflammation-driven cardiovascular disease, positioning MPO as a promising therapeutic target. However, substantial interspecies differences between murine and human neutrophil biology challenge the translation of preclinical findings from rodent studies into patients. METHODS: 11,608 patients were screened for MPO deficiency using the ADVIA 2120i system. 282 individuals exhibited a reduced MPO activity. 56 patients were eligible, consented to be enrolled and were compared to 20 control patients. MPO levels and activity were measured by enzyme-linked immunosorbent assay (ELISA), immunoblotting, a tetramethylbenzidin (TMB)-based peroxidase and nitric oxide (NO)-consumption assay. For cross-species analysis, shotgun proteomics, Gene Ontology (GO) and REACTOME pathway enrichment analyses were conducted on bone marrow derived PMNs from Mpo-/- mice and human MPO-deficient PMNs. RESULTS: Patients with persistent (MPOlow, n = 12) and transient (MPOrec, n = 44) MPO deficiency were identified. MPOlow individuals showed significantly decreased neutrophil MPO concentrations, enzymatic activity, and plasma MPO levels. Proteomic profiling revealed substantial overlap in altered biological processes across both species. Species-specific enrichments included humoral immunity, complement activation, and coagulation in humans, phagocytosis, chemotaxis, and transcriptional regulation in mice. These differences have been reported alongside distinct signaling patterns, with predominance of Mitogen-activated protein (MAP)-kinase and cytokine activity in humans, and Ras homolog family (Rho)-GTPase pathways in mice. CONCLUSION: MPO deficiency leads to broadly conserved alterations in neutrophil immune and stress responses across humans and mice. However, similar functional outcomes may involve different signaling pathways in each species contributing to divergent phenotypes in disease models. These findings underscore species-specific mechanisms in MPO-related neutrophil biology and highlight critical considerations for translating MPO-targeted therapies from animal models to human disease.

Primary hyperhidrosis is termed as excessive sweating exceeding the physiological needs of thermoregulation. This review provides an updated overview focusing on epidemiology, quality of life, pathophysiology, economic impacts, diagnostic approaches and current management strategies. A literature search was conducted in June 2026 across PubMed and the Cochrane Central Register of Controlled Trials. Additional references were identified through manual searches of relevant bibliographies. Reported prevalence of hyperhidrosis varied widely, likely reflecting differences in methodology and disease recognition. Primary hyperhidrosis is associated with autonomic dys-regulation involving sympathetic pathways. Emerging evidence suggests that molecular alterations in eccrine glands may represent secondary adap-tations to sustained cholinergic stimulation, while genetic variability in receptor expression may contribute to interindividual differences in disease severity. Hyperhidrosis has a strong negative impact on the economy and quality of life, adversely affecting both mental and physical health. Multiple treatment options are available, including topical therapies, systemic agents, device-based interventions, botulinum toxin injections, and surgery. Despite increasing recognition of the clinical burden, comprehensive economic evaluations remain limited, with indirect costs and long-term societal impact insufficiently characterized. In conclusion, primary hyperhidrosis imposes a substantial burden on affected individuals, requiring improved re-cognition, standardized diagnostic frameworks, and individualized management strategies supported by high-quality and longitudinal research.

PURPOSE: Hidradenitis suppurativa (HS) is a benign, chronic inflammatory condition involving painful lesions that can progress to abscesses, skin tunnels, and fibrotic scars. Treatment of recalcitrant disease often involves immunomodulatory agents or surgery, but these often result in modest improvement. This study's objective was to determine the effectiveness of external beam low-dose radiation therapy (LD-RT) as an adjunct treatment for recalcitrant HS. METHODS AND MATERIALS: HS patients receiving LD-RT at a single institution from 2017 to 2024 were retrospectively identified. LD-RT dose included 750 cGy in 3 fractions or 800 cGy in 4 fractions. Patient demographics and comorbidities were recorded. Treatment response was categorized as excellent, partial, or no response, and site-specific symptoms were recorded based on available records. RESULTS: Thirteen patients with HS underwent LD-RT to 38 sites were identified with a median follow-up period of 1.45 years from completion of LD-RT (range, 0.4-7 years). The majority of sites were Hurley stage III (34/38). At the patient level, all had been previously treated with antibiotics, 9 with prednisone, 12 with biologic agents, and 7 with a surgical procedure. Clinical response per site included 4 of 38 (10.5%) excellent, 26 of 38 (68.4%) partial, and 8 of 38 (21.1%) nonresponders. Four patients reported a reduction in pain score at first radiation oncology follow-up. For those with a response, median time from LD-RT to next rescue intervention was 2.2 months (range, 0.6-23.1 months). Three sites underwent surgery at a median time of 9.3 months from LD-RT completion. Two patients with 5 sites were retreated without response 1 year after LD-RT. CONCLUSION: LD-RT for HS demonstrates high rates of response, with the majority of treated areas having some subjective improvement in disease burden, although most only have partial improvement. Need for rescue intervention shortly after this treatment is common.

Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus (JCPyV). PD-1 checkpoint immunotherapy has benefited some PML patients, but reasons for its variable outcomes are unclear. Using mouse polyomavirus (MuPyV), we show that PD-1 loss acts in a brain-autonomous manner to increase the magnitude of brain-infiltrating CD4+ and CD8+ T cells and the function of virus-specific CD8+ T cells; in concert, brain virus levels decline and neuroinflammation increases. Deletion of PD-1 in CD4+ T cells, but not CD8+ T cells, recapitulates effects of global PD-1 loss. Single-cell RNA sequencing shows that PD-1-deficient CD8+ T cells cluster as effectors while transcripts associated with proliferation and function are upregulated with loss of PD-1. Thus, CD4+ T cell-intrinsic PD-1 signaling balances antiviral defense against neural injury during polyomavirus infection of the brain.