Neurological Sciences最新文献

Background: To date, neuromyotonia in the context of an inherited axonal neuropathy has been linked to autosomal recessive mutations in the histidine triad nucleotide binding protein 1 (HINT1) gene. In this study we describe two unrelated male patients with late-onset, predominantly motor, axonal neuropathy with neuromyotonia, who carried an autosomal dominant c.103G > A mutation in the myelin protein zero (MPZ) gene (NM_000530.8:c.103G > A, p.Asp35Asn), identified by whole-exome sequence analysis (WES).  CASE DESCRIPTIONS: The first patient presented progressive leg muscle weakness and stiffness with difficulty in walking, pain and increased creatine kinase levels,during his fifth decade of life. Electrophysiological examination revealed findings of an axonal, length-dependent polyneuropathy with spontaneous activity, mainly neuromyotonia. Over the 20-year disease course since the first reported symptoms, muscle weakness gradually worsened and he is currently unable to walk without assistance. A second male patient, unrelated to the first one, showed similar clinical and electrophysiological features of a length-dependent axonal neuropathy with neuromyotonia. WES detected the same MPZ missensevariant.  CONCLUSION: This study suggests a novel entity in the spectrum of Charcot-Marie-Tooth hereditary neuropathies, characterized by autosomal dominant axonal neuropathy with neuromyotonia (AD-NMAN).

The progress of biomedical technologies has expanded the boundaries of care, offering new treatment options and prolonging patients' survival even in conditions of great suffering and dependence. End-of-life decisions are an important topic in contemporay bioethics and physician-assisted suicide (PAS) is a still controversial topic, with Neurology at the forefront.This glossary provides a set of definitions to improve clarity and use of a consistent language in the bioethical debate on patients' autonomy, treatment limitations, palliative care, PAS, euthanasia, and related issues. The objective of the glossary, which is aligned with most recent international consensus documents and with the italian regulatory frameworks, is to clarify and harmonize the practical use of terms.The glossary, together with the companion paper outlining the position of the Italian Society of Neurology (SIN) regarding PAS, are living documents subject to revision. They can serve as a foundation for a pluralistic discussion in the debate on the ethical issues related to the care of individuals with neurological diseases characterized by poor prognosis in terms of severe disability or limited biological and biographical life expectancies, as well as their families and caregivers. An even more ambitious goal of these documents is to enhance research and inform the development of national regulation in these areas.

Background: One of the most social consequences of Multiple Sclerosis (MS) is a reduction in employability that occurs early in the disease. The aim of the study is to explore the factors contributing to specific work-related difficulties, including main functions affected by MS.

Methods: The study involved two Italian centers and included subjects with MS diagnosis of working age (18-65 years) and currently employed. Subjects underwent an evaluation to investigate work-related difficulties, socio-occupational data and the main clinical domain affected by MS with an impact on work-related difficulties, such as walking, balance, upper limb and cognitive functions, mood and fatigue. Linear regression analysis was used to examine the direction and size of the relationships between specific work-related difficulty and the variables examined.

Results: A total of 82 subjects with MS were recruited (59.8% of females, mean age 44.0 (SD: 10.7) years, a mean EDSS score of 3.7 (SD: 2.4); mean education of 15.2 (SD: 4.2) years). The 36.6% of the sample resulted having work-related difficulties with a possible consequent risk of job lost. Our results highlighted that objective assessment of walking and balance, upper limb and cognitive functions were not significant determinants of any specific work-related difficulties. However, the key factors most strongly associated with work challenges are the presence of depressive symptoms, followed by physical and cognitive fatigue.

Conclusion: Identifying the main factors related to work difficulties is a fundamental step to prevent the manifestation of these difficulties and develop tailored intervention for job retention.

Background and objective: Tuberous sclerosis complex (TSC) is a hereditary disorder that leads to tumor growth in various organs. Manifestations from mutations in the TSC1 or TSC2 genes comprise seizures, developmental delay, and skin abnormalities. This literature search has been dedicated to emphasizing the critical role of early diagnosis and the formulation of individualized plans for this target population with co-occurring TSC and Autism Spectrum Disorder (ASD).

Experimental procedure: Behavioral and developmental tests can evaluate ASD symptoms; neuroimaging methods like functional MRI and PET scans can identify brain abnormalities, and molecular genetic analysis can detect TSC1/TSC2 mutations. Differential Diagnostic Approach These include medical histories and physical examinations to consider that ASD and TSC present the same symptoms.

Results: Although 90% of TSC patients are reported to have TSC-associated neuropsychiatric disorders, 30-50% of patients fulfil the clinical criteria of ASD. In comparison, the estimate for the rate of ASD prevalence in TSC patients ranges from 17 to 63%, with the characteristics of infantile spasms and early-onset epilepsy. The diagnosis is further challenged by the fact that there are shared symptoms between both, namely seizures and intellectual impairment.

Conclusion: The shared symptoms between TSC and ASD suggest the need for multidisciplinary approaches in both diagnosis and treatment. A personalized therapeutic plan should include behavioral therapy, medication with Everolimus, mammalian target of rapamycin (mTOR) inhibitors, and advanced neuroimaging. The future of research in biomarkers, molecular medicines, and improving diagnostic protocols holds great promise for optimizing patient care and treatment options.

Background: Intravenous thrombolysis (IVT), utilizing the clot-dissolving medications alteplase (rt-PA) or tenecteplase (TNK), is the cornerstone in acute ischemic stroke (AIS) emergency intervention. However, the impact of prior antiplatelet therapy (APT) on post-IVT outcomes when utilizing alteplase remains controversial. We conducted a systematic review and meta-analysis to evaluate the effect of prior APT on the outcomes after using alteplase in AIS patients.

Methods: We conducted a systematic review and meta-analysis synthesizing studies, which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through June 30, 2024. We used the R language V. 4.3. to pool dichotomous data using odds ratio (OR) with a 95% confidence interval (CI).

Prospero id: CRD42024495393.

Results: Thirty studies were included in our analysis, with 436,232 patients. Prior APT was significantly associated with increased odds of symptomatic intracranial hemorrhage (sICH) (OR, 1.78; 95%CI [1.48, 2.13]; P < 0.01), any ICH (OR, 1.44; 95%CI [1.16, 1.78]; P < 0.01), mortality (OR, 1.39; 95%CI [1.23, 1.58]; P < 0.01), and poor functional outcomes (modified Rankin Scale score of 3-6 [mRS 3-6]) (OR, 1.81; 95%CI [1.03, 3.19]; P = 0.04). Additionally, prior APT significantly reduced the odds of good functional outcome [mRS 0-2] (OR, 0.85; 95%CI [0.74, 0.97]; P = 0.02).

Conclusion: Prior APT increased hemorrhagic complications, mortality, and poor functional outcome, while reducing the odds of good functional outcome after IV alteplase. Future research should focus on identifying adjunctive agents that may decrease hemorrhagic complications and investigate the impact of various APT regimens and alternative thrombolytics beyond alteplase in this specific population.

The COL12A1 gene encodes Collagen XII α 1 chain, forming a biologically functional Collagen XII through a trimeric structure. Collagen XII dysfunction can lead to hereditary neuromuscular diseases with phenotypic profiles ranging from rare Ullrich congenital muscular dystrophy 2 (biallelic variant) to Bethlem myopathy 2 (uniallelic variant). Currently, only 29 COL12A1 deficiency cases have been reported, mainly featuring hypotonia, progressive muscular dystrophy, and skeletal deformities. Newborns cases were relatively rare. Here, we describe a neonate with hypotonia, weak spontaneous movement, convulsions, and respiratory failure at birth. Identification of a novel variant of COL12A1 by whole exome sequencing and Sanger sequencing, NM_004370.6: c.7622 C > T, p.Ser2541Phe. Molecular dynamics simulation revealed its location in the thrombospondin N-terminal domain, potentially destabilizing the Collagen XII trimer's structure. Our case report expands the COL12A1 genotype and phenotype spectrum, suggesting the presence of neonatal hypotonia and highlighting the importance of vigilance for respiratory clinical manifestations.

Background: Although fibromyalgia is a disabling disease, there is no targeted therapy for specific neurotransmitters or inflammatory mediators. Our aim was to provide neurologists with practical guidance for the management of these difficult patients based on a critical, narrative and non-systematic review of randomized controlled trials (RCTs) from the last 10 years.

Methods: The members of the Special Interest Group Neuropathic Pain of the Italian Neurological Society evaluated the randomized controlled trials (RCTs) of the last 10 years and answered questions that allow a consensus on the main pharmacological and non-pharmacological approaches.

Results: The neuropathic pain working group agreed on prescribing antiepileptic drugs or antidepressants in the case of comorbidities with anxiety and depression. As a second choice, experts have agreed on the association of antiepileptics and antidepressants, while they disagree with the use of opioids. Medical cannabis and nutraceuticals are promising new treatment options, although more data is needed to prove their efficacy. The neurologists agreed in suggesting physical activity at the first visit, particularly aerobic and strength training. As a second choice, they considered a cognitive behavioral therapy approach to be useful.

Conclusions: Pharmacologic treatment with antiepileptic drugs and antidepressants in patients with co-occurring anxiety and depression, as well as an early nonpharmacologic approach based primarily on physical activity, may be a useful indication in contemporary neurology clinical practice. Non-pharmacological options, such as cognitive behavioral therapy and non-invasive brain stimulation NIBS, could improve evidence of efficacy and lead to relevant improvement in FM-related disability.

Background: Premorbid sarcopenia in acute stroke indicates poor prognosis. Since formal sarcopenia tests cannot be performed, the muscle features imaged in diagnostic studies are opportunistically used as surrogates for sarcopenia in the acute period.

Methods: In 110 consecutive acute ischemic anterior circulation stroke patients treated with intravenous tissue plasminogen activator alone (mean age: 73±13 years, 55% women), the cross-sectional area (CSA) and attenuation of pectoralis major and minor muscles and mediastinal adipose tissue were measured at admission computed tomography (CT) angiography source images.

Results: Pectoralis major and minor muscle CSA (mm²) and indices (CSA/height(m)²) were significantly higher in patients with 3-month modified Rankin's scores of 0-1 (excellent outcome, 41%), 0-2 (good outcome, 54%), and in surviving patients (87%). In regression models adjusted for age and NIHSS, pectoralis major muscle CSA (partial r: -0.281, p = 0.027) and pectoralis major index (partial r: -0.332, p = 0.008) were independent predictors of mortality. The discriminatory value of the pectoralis major index for mortality was good (ROC-AUC 0.794, 95%CI: 0.676-0.885). The optimal threshold for survival of pectoralis major index was > 3316 mm²/m² with 0.607 Youden J index. No difference was found in muscle CT attenuation values, mediastinal adipose tissue area and radiodensity in deceased patients.

Conclusions: Our retrospective analysis documents that the pectoralis major index, a readily available CT anthropometry surrogate for sarcopenia, is an independent predictor of survival in patients with acute ischemic stroke undergoing systemic thrombolysis. It may suggest that the pectoralis major index could be included in the prognostic toolkit of acute ischemic stroke.

Objective: We investigated the effects of Subthalamic Deep Brain Stimulation (STN-DBS) at high (180hz) and low frequency (60hz) and L-dopa on variability of spatiotemporal gait measures in an advanced PD cohort.

Materials and methods: This study consisted of PD subjects with chronic bilateral STN-DBS. Each combination of medication state (OFF/ON) and stimulation frequency (60 Hz/180Hz) were assessed and randomized across electrode contacts. Instrumented stand and walk tests were performed for each stimulation-medication condition and coefficient of variance (CV) was computed for each lower limb gait parameter. LM-ANOVA was employed for analysis.

Results: Twenty-two PD subjects with chronic DBS were recruited with an average age of 63.9(SD 9) years. L-dopa reduced variability in both spatial and temporal gait parameters: cadence (L/R, p < 0.0001), gait speed (L/R, p < 0.0001), toe off angle (L/R, p < 0.0001), SLS (L, p = 0.0002; R, p = 0.001), stance (L, p = 0.01, R, p < 0.0001;), step duration (L, p < 0.0001; R, p = 0.004), stride length (L/R, p < 0.0001), and foot swing (L, p = 0.0003; R, p < 0.0001). Low and high frequency DBS reduced variability in cadence, foot elevation midswing, speed, right foot strike angle, SLS, stand, step duration, stride length, and foot swing. 60 Hz STN-DBS synergistically reduced left foot mid-swing elevation variability (p = 0.02) when combined with medication.

Conclusion: This study demonstrates significant reduction in variability of spatial and temporal gait measures from L-dopa and STN-DBS. It further reveals a synergistic effect of 60Hz STN-DBS with L-dopa in reducing foot elevation midswing variability.