Acta neurologica Belgica最新文献

Objective: To evaluate sleep architecture disruptions in amyotrophic lateral sclerosis (ALS) using polysomnography (PSG) and identify clinical/demographic correlates for targeted interventions.

Methods: Forty definite/probable ALS patients (revised El Escorial criteria) without primary sleep disorders and 40 age/sex/BMI-matched controls underwent full polysomnography (PSG). Sleep parameters (total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], N1-N3, rapid eye movement [REM] sleep), respiratory indices (AHI, minimum peripheral oxygen saturation (min SpO₂), SpO₂ range/coefficient of variation [CV]), and clinical metrics (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R], Hospital Anxiety and Depression Scale [HADS]) were compared. Multivariate regression identified independent sleep predictors, and mediation analysis quantified min SpO₂'s role in age-sleep fragmentation relationships.

Results: ALS patients showed significantly reduced TST (371.54 ± 67.62 vs. 495.13 ± 45.69 min, p = 0.004), SE (69.95 ± 13.79 vs. 85.10 ± 7.03%, p = 0.009), N2 sleep (127.33 ± 56.75 vs. 204.28 ± 67.16 min, p = 0.013), N3 sleep (61.70 ± 33.67 vs. 91.90 ± 44.06 min, p = 0.021), and REM sleep (66.09 ± 35.85 vs. 84.66 ± 37.65 min, p = 0.012) alongside elevated WASO (131.70 ± 78.82 vs. 64.26 ± 44.18 min, p = 0.015). Nocturnal oxygenation was impaired (min SpO₂: 89.3 ± 3.1% vs. 93.7 ± 2.4%, p < 0.001; SpO₂ CV: 3.7 ± 1.5% vs. 1.8 ± 0.9%, p < 0.001), though AHI and REM AHI were comparable (AHI: p = 0.087; REM AHI: p = 0.134). Age (β = -0.28, p = 0.02) and min SpO₂ (β = 0.31, p = 0.01) independently predicted TST. Mediation analysis confirmed min SpO₂ partially explains age-related TST reduction (indirect effect: -0.14, 95% CI: -0.28 to - 0.03; accounting for 43.8% of the total effect).

Conclusion: Our data confirm profound sleep architecture disruption and nocturnal hypoxemia in ALS independent of primary sleep disorders. Critically, we establish min SpO₂ as a partial mediator of age-related sleep fragmentation, suggesting that early management of hypoxemia may improve sleep quality. Larger prospective studies validating these mechanisms and their impact on disease progression are warranted.

Chimeric Antigen Receptor T-cell (CAR-T) therapy has significantly improved outcomes in hematologic malignancies but may lead to rare and severe neurological complications beyond immune effector cell-associated neurotoxicity syndrome (ICANS), such as acute myelopathy. We report the case of a 59-year-old woman treated with CD19-targeted CAR-T cells for relapsed lymphoma, who developed grade IV ICANS followed by a clinical presentation of myelitis attributed to CAR T-cell therapy after exclusion of alternative diagnoses. Aggressive immunosuppressive treatment and supportive care failed to achieve neurological recovery. The patient remained ventilator-dependent due to cervical spinal cord lesions and ultimately died following transition to palliative care. This case underscores the diagnostic challenges posed by this medical emergency in critically ill patients since numerous confounding factors may obscure early signs of spinal cord involvement in the ICU setting. Early neurologic evaluation and multidisciplinary management are critical. This case aims to raise awareness on this rare yet dramatic complication, in which prompt initiation of treatment may prevent long term sequelae.

Myoclonus-Dystonia (M-D) is a rare autosomal dominant disorder predominantly characterized by myoclonus and focal or segmental dystonia. Symptoms typically onset during childhood and are often triggered by specific postures or actions. SGCE gene mutations are the main cause of M-D. The SGCE gene is located on the chromosomal region 7q21 and encodes the ε-sarcoglycan protein. Inheritance follows a paternal transmission pattern with maternal imprinting. Although studies on M-D have expanded, the pathophysiological mechanisms remain to be fully elucidated. To better understand the comprehensive review of SGCE-related M-D (SGCE-M-D), this article focuses on its the clinical manifestations, molecular genetics, pathophysiological mechanisms, and therapeutic strategies in SGCE-M-D. Additionally, we present a schematic illustrating the distribution of SGCE gene variants at the amino acid level.

Purpose of review: The escalating global burden of neurodegenerative diseases, coupled with a lack of disease-modifying therapies, has intensified the search for modifiable risk factors. This review aims to synthesize the extensive recent literature to position the brain's waste clearance pathway, the glymphatic system, as a core physiological bridge connecting disordered sleep to the molecular pathogenesis of neurodegeneration, thereby providing a coherent mechanistic framework for clinicians and researchers.

Recent findings: Compelling evidence from the last decade solidifies the glymphatic system's dependence on deep, non-rapid eye movement (NREM) sleep for the efficient clearance of neurotoxic metabolic byproducts, including amyloid-beta (Aβ), tau, and α-synuclein. Common and highly prevalent clinical conditions, including obstructive sleep apnea (OSA), chronic insomnia, and circadian rhythm disorders, have been shown to fundamentally disrupt this vital clearance process. The pathogenic drivers are multifactorial, involving sleep fragmentation-induced sympathetic hyperactivity, intermittent hypoxia-driven vascular damage, and neuroinflammatory activation. Glymphatic impairment is a key, non-redundant pathophysiological mediator between sleep disorders and the initiation and propagation of neurodegenerative cascades. This understanding elevates the status of sleep from a passive correlate to an active, modifiable factor in brain health. Consequently, the systematic diagnosis and effective management of sleep disorders emerge as tangible, accessible, and powerful strategies for primary and secondary neuroprotection.