Neurological Sciences最新文献

Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare inherited white matter disorder. Initially, a "classic" phenotype has been characterized, presenting early-onset macrocephaly, cerebellar ataxia, mild spasticity, and a distinctive neuroimaging pattern of diffuse white matter abnormalities with subcortical cysts. An "improving" phenotype has also been described, featuring milder or absent neurological signs and a remitting pattern on neuroimaging. Mutations in four genes, MLC1, HEPACAM, GPRC5B and AQP4 have been associated with MLC. We describe clinical and genetic features of a cohort of genetically confirmed Italian MLC patients, representing the largest Italian cohort reported to date.

Materials and methods: We conducted a retrospective, multicenter, observational study. Patients were included based on clinical and neuroimaging features consistent with MLC, along with a confirmed genetic diagnosis. Data were collected using a standardized database and included demographic, clinical, neuroimaging, neurophysiological, and genetic information.

Results: Thirty-three patients from eight Italian centers were enrolled. Twenty-seven harbored biallelic MLC1 variants (23 distinct mutations, including three novel variants), while six had three distinct heterozygous HEPACAM variants. All MLC1-mutated patients exhibited the "classic" phenotype, frequently accompanied by orthopedic, gastrointestinal, and respiratory comorbidities. HEPACAM-mutated patients were consistent with the "improving" phenotype. No patients harbored mutations in GPRC5B or AQP4.

Conclusions: Our findings expand the mutational spectrum of MLC1, further characterize the disease phenotype, and provide valuable insights into its presence in Italy. They also underscore management needs of individuals with MLC, highlighting the importance of multidisciplinary care.

Background: Idiopathic cervical dystonia (ICD) is a chronic movement disorder characterized by involuntary neck muscles contractions, leading to pain, disability, and poor quality of life. While botulinum toxin (BTX) type A is the first-line treatment, its efficacy on non-motor symptoms is limited. Physical therapy (PT) may act synergistically and improve functional outcomes.

Objective: To evaluate whether BTX with tailored PT yields superior clinical outcomes compared to BTX alone in ICD patients, focusing on motor severity, disability, pain,mood, and quality of life.

Methods: This is a monocentric crossover trial on adults with ICD receiving stable BTX. They were randomized to two treatment sequences (BTX → BTX+PT or BTX+PT → BTX), with a 4-week washout. PT consisted of a six-week individualized program including daily home exercises and weekly supervised sessions. Outcomes were assessed using TWSTRS, BDI-II, SAS, and CDIP-58.

Results: Among 20 enrolled patients, 18 completed the trial. Both treatments improved TWSTRS total scores (p = 0.0001), with greater improvement in the BTX+PT group (p = 0.0024). PT addition significantly reduced disability (p = 0.0024), pain (p = 0.0024), and depression (p = 0.0089). Anxiety improved, without significant between-group differences. CDIP-58 scores showed greater quality-of-life gains with BTX+PT (p < 0.0001).

Conclusions: BTX with PT shows greater effectiveness than BTX alone in managing ICD, improving motor and non-motor symptoms. These findings support the integration of individualized PT into standard care to optimize clinical benefits.

Background: The incidence of acute ischemic stroke (AIS) is increasing among young to middle-aged adults (18-64 years), posing substantial socioeconomic and healthcare challenges. This study aimed to evaluate the diagnostic and predictive value AHR, Klotho, and sdLDL-C in AIS and across different TOAST etiological subtypes in this age group.

Methods: We retrospectively enrolled young to middle-aged patients with first-ever AIS and age- and sex-matched stroke-free controls. All participants underwent DWI and additional vascular assessments, including MRA, CTA, and/or DSA. Clinical characteristics, imaging findings, and laboratory parameters were statistically analyzed. Patients were classified into TOAST subtypes for etiological analysis.

Results: Multivariate logistic regression identified male sex, DBP, FPG, LDL-C, and DWM as independent risk factors for AIS. The most common TOAST subtype was SAO, followed by SUE and LAA. Compared to controls, AIS patients exhibited significantly higher AHR and sdLDL-C levels and lower Klotho levels (all P < 0.001). ROC analysis demonstrated that the combined use of AHR, Klotho, and sdLDL-C had high diagnostic accuracy for AIS (AUC = 0.971), with the highest predictive value observed for LAA subtype (AUC > 0.9).

Conclusion: In young to middle-aged adults, male sex, elevated DBP, FPG, LDL-C, and DWM are independent risk factors for AIS. AHR and sdLDL-C are positively associated with AIS risk, while Klotho is inversely associated. The combined biomarker panel (AHR, Klotho, and sdLDL-C) demonstrates strong diagnostic utility, particularly for identifying the LAA subtype. These findings provide valuable insight into early risk stratification and classification of AIS in younger populations.

Introduction: Insomnia is a common sleep disorder characterized by difficulty initiating or maintaining sleep, significantly impacting daytime functioning and quality of life. Its chronic nature, high prevalence among older adults, and association with multiple comorbidities make it a pressing health concern. Here, we provide an overview of insomnia in the elderly, highlighting the gap between scientific guidelines and real-world clinical practice and the common pitfalls in managing this fragile patient population.

Methods: We performed a comprehensive literature review to synthesize recent findings on insomnia pathophysiology, diagnosis, and treatment in the aging population.

Results: Insomnia in the elderly is frequently intertwined with comorbidities, which both contribute to and are exacerbated by sleep disturbances. The diagnostic process is complex, requiring differentiation between primary insomnia and conditions influenced by comorbidities, medications, and age-related sleep changes. A comprehensive clinical assessment remains the cornerstone of diagnosis. Treatment prioritizes non-pharmacological strategies, with cognitive-behavioral therapy for insomnia as the first-line approach, though accessibility remains a challenge. Pharmacotherapy should be reserved for short-term use, with careful consideration of adverse effects. However, pharmacological treatment often becomes chronic and deviates from clinical recommendations, relying on off-label medications. Insomnia management is further complicated by polypharmacy, which disrupts sleep and increases the risk of drug interactions and side effects, including falls and cognitive decline.

Conclusions: A multidimensional, patient-centered approach is essential for managing insomnia in older adults. Addressing comorbidities, optimizing pharmacological strategies, and improving access to non-pharmacological treatments are crucial steps towards enhancing outcomes and quality of life in this vulnerable population.

Background: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder typically presenting with subacute, painless, bilateral vision loss in young individuals. While often recognizable, atypical presentations can complicate diagnosis. Notably, optic nerve lesions on MRI are uncommon in LHON and are typically associated with inflammatory optic neuropathies, increasing the risk of misdiagnosis.

Methods: We retrospectively analyzed four patients who initially presented with suspected optic neuritis but were later diagnosed with LHON. Demographic, genetic, clinical, and multimodal data were retrieved from medical records.

Results: The series included two adolescent males, a 51-year-old man, and a 52-year-old woman. All experienced subacute, bilateral vision loss and were later found to carry pathogenic LHON mutations. However, their initial presentations were misleading. The two adult patients presented beyond the typical age of onset; one was initially diagnosed with glaucoma due to increased intraocular pressure, while the other had a history of Fahr's syndrome. One adolescent reported ocular pain with eye movements and showed a relative afferent pupillary defect, mimicking optic neuritis. Two patients lacked typical fundoscopic findings suggestive of LHON. MRI findings further complicated the diagnosis: all patients showed T2-FLAIR hyperintensities of the optic nerves with contrast enhancement, and in three cases abnormalities extended posteriorly to the chiasm and optic tracts on follow-up MRI.

Conclusion: MRI abnormalities involving the optic pathway do not exclude LHON and may be present in atypical cases. LHON should be considered in all patients presenting with bilateral subacute visual loss, even when clinical or imaging features suggest alternative diagnoses.