Neurology International最新文献

Background/objectives: Elderly patients with carpal tunnel syndrome (CTS) have more severe clinical, ultrasonic, and electrodiagnostic (EDX) findings compared to younger patients. Thenar weakness and atrophy are more common at initial presentation in the elderly population with CTS.

Methods: This is a retrospective review of 187 very elderly patients (aged 80 years and older) with EDX confirmation of CTS. We describe the clinical, EDX, and US features in these patients and compare the severity of the median nerve entrapment at the carpal tunnel (CT) by EDX findings to a middle-aged cohort (ages 40-50 years).

Results: The total number of very elderly hands with CTS was 289 (187 patients total, with bilateral symptoms in 102 patients). Of the 289 hands, thenar atrophy was observed in 75 (26.0%) hands, weakness of the abductor pollicis brevis (APB) muscle was detected in 178 (61.6%) hands, and pinprick decrease/loss was noted in 265 (91.7%) hands. Of the total 289 hands, 57 (66.3%) hands' median nerve stimulation did not evoke compound muscle action potentials over the APB and second lumbrical muscles. Sensory nerve action potentials were not detected in 211 (76.2%) hands. Comparing the sensitivities of various US measurements in diagnosing CTS, the cross-sectional area at the CT inlet had the highest sensitivity among the various measurements. As the CSA at the CT inlet increases, the odds of a greater CTS severity by EDX studies also increase (OR = 1.109, p-value = 0.001). The very elderly patients with CTS more frequently had more severe CTS compared to the middle-aged patients with CTS (chi-squared = 102.65₃, p-value < 0.001).

Conclusions: The very elderly patients appear to seek medical care only when the CTS has become severe. The primary care physicians should look for signs and symptoms of CTS in the very elderly and encourage prompt treatment. Surgeons should be cognizant of the differences in the clinical, EDX, and US studies in the very elderly patient cohort with CTS. US is highly useful in evaluating CTS when the EDX studies become non-localizing in severe CTS, as often seen in the very elderly patients.

Background: The pathophysiology of epilepsy is characterized by increased neuronal activity due to an excess of the excitatory neurotransmitter glutamate and a deficiency in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Epilepsy presents with seizures, neuronal loss, and hyperactivity in the subthalamic nucleus (STN). Astrocytes play a crucial role by absorbing extracellular glutamate through glutamate transporter-1 (GLT-1), thereby reducing neuronal excitation. Upregulating the expression of astrocytic GLT-1 is a promising therapeutic strategy for epilepsy. Sulbactam (SUL), a β-lactam antibiotic, has been demonstrated to exert neuroprotective effects by upregulating GLT-1 expression. Objectives: This study investigated the impact of SUL on neuronal and behavioral changes in epilepsy by using a pentylenetetrazol (PTZ)-induced rat model of epilepsy. Methods: Rats were treated with saline, SUL (50 and 150 mg/kg), or a combination of SUL and the GLT-1 blocker dihydrokainate (DHK) for 20 days. Subsequently, behavioral tasks were conducted to assess recognition, anxiety, and memory. Results: Histological analyses revealed that SUL ameliorated neuronal deficits, increased astrocytic GLT-1 expression, and reduced hyperactivity in the STN. Additionally, SUL promoted astrocyte proliferation, indicating a new dimension of its neuroprotective properties. However, the beneficial effects of SUL were prevented by DHK. Conclusions: This pioneering study highlights multiple benefits of SUL, including seizure suppression, increased GLT-1 expression, and astrocyte proliferation, underscoring its high potential as a treatment for epilepsy.

Background/objectives: Acute ischemic stroke is a leading cause of mortality and long-term disability globally, with limited reliable early predictors of functional outcomes and survival. This study aimed to assess the prognostic value of two novel predictors: the hypoperfusion intensity ratio calculated from mean transit time and time-to-drain maps (HIR-MTT-TTD), derived from computed tomography perfusion (CTP) imaging parameters, and the Inflammation-Coagulation Index (ICI), which integrates systemic inflammatory (C-reactive protein and white blood cell count) and hemostatic (D-dimer) markers.

Methods: This prospective, single-center observational study included 60 patients with acute ischemic stroke treated with intravenous thrombolysis and underwent pre-treatment CTP imaging. HIR-MTT-TTD evaluated collateral status and perfusion deficit severity, while ICI integrated C-reactive protein (CRP), white blood cell (WBC) count, and D-dimer levels. Functional outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Barthel Index, and modified Rankin Scale (mRS) at 24 h, 3 months, and 1 year.

Results: Of 60 patients, 53.3% achieved functional independence (mRS 0-2) at 1 year. Unadjusted Cox models showed HIR-MTT-TTD (HR = 6.25, 95% CI: 1.48-26.30, p = 0.013) and ICI (HR = 1.08, 95% CI: 1.00-1.17, p = 0.052) were associated with higher 12-month mortality, worse mRS, and lower Barthel scores. After adjustment for age, BMI, smoking status, and sex, these associations became non-significant (HIR-MTT-TTD: HR = 2.83, 95% CI: 0.37-21.37, p = 0.314; ICI: HR = 1.07, 95% CI: 0.96-1.19, p = 0.211). Receiver operating characteristic (ROC) analysis indicated moderate predictive value, with ICI (AUC = 0.756, 95% CI: 0.600-0.867) outperforming HIR-MTT-TTD (AUC = 0.67, 95% CI: 0.48-0.83) for mortality prediction.

Conclusions: The study introduces promising prognostic tools for functional outcomes. Elevated HIR-MTT-TTD and ICI values were independently associated with greater initial stroke severity, poorer functional recovery, and increased 1-year mortality. These findings underscore the prognostic significance of hypoperfusion intensity and systemic thrombo-inflammation in acute ischemic stroke. Combining the use of the presented indices may enhance early risk stratification and guide individualized treatment strategies.

Background: Accurate differentiation of Parkinson's disease (PD) from healthy aging is crucial for timely intervention and effective management. Postural sway abnormalities are prominent motor features of PD. Quantitative stabilometry and machine learning (ML) offer a promising avenue for developing objective markers to support the diagnostic process. This study aimed to develop and validate high-performance ML models to classify individuals with PD and age-matched healthy older adults (HOAs) using a comprehensive set of stabilometric parameters. Methods: Thirty-seven HOAs (mean age 70 ± 6.8 years) and 26 individuals with idiopathic PD (Hoehn and Yahr stages 2-3, on medication; mean age 66 years ± 2.9 years), all aged 60-80 years, participated. Stabilometric data were collected using a force platform during quiet stance under eyes-open (EO) and eyes-closed (EC) conditions, from which 34 parameters reflecting the time- and frequency-domain characteristics of center-of-pressure (COP) sway were extracted. After data preprocessing, including mean imputation for missing values and feature scaling, three ML classifiers (Random Forest, Gradient Boosting, and Support Vector Machine) were hyperparameter-tuned using GridSearchCV with three-fold cross-validation. An ensemble voting classifier (soft voting) was constructed from these tuned models. Model performance was rigorously evaluated using 15 iterations of stratified train-test splits (70% train and 30% test) and an additional bootstrap procedure of 1000 iterations to derive reliable 95% confidence intervals (CIs). Results: Our optimized ensemble voting classifier achieved excellent discriminative power, distinguishing PD from HOAs with a mean accuracy of 0.91 (95% CI: 0.81-1.00) and a mean Area Under the ROC Curve (AUC ROC) of 0.97 (95% CI: 0.92-1.00). Importantly, feature analysis revealed that anteroposterior sway velocity with eyes open (V-AP) and total sway path with eyes closed (TOD_EC, calculated using COP displacement vectors from its mean position) are the most robust and non-invasive biomarkers for differentiating the groups. Conclusions: An ensemble ML approach leveraging stabilometric features provides a highly accurate, non-invasive method to distinguish PD from healthy aging and may augment clinical assessment and monitoring.

In Alzheimer's disease, accumulation of Aβ and tau aggregates in the limbic and cortical regions of the brain forms the pathological basis for the onset of memory loss and cognitive abnormalities. The neuronal desecration inflicted by these toxic pile-ups will rouse the onset of innate immune defense mechanisms including astrogliosis within the neuronal milieu. A potential ramification of astrogliosis is the overproduction and spillage of GFAP into the brain circulation. Execution of GFAP vital physiological functions rests upon the preservation of its filamentous structure as well as its cytoskeletal interactions. Any anomaly that hampers the structural integrity of GFAP will engender filament disassembly, cytoplasmic aggregation, and decreased solubility with the resultant deleterious consequences. The potency of GFAP as a reliable biomarker in the blood also rests on its ability to navigate the glymphatic excretory pathways and spill into the systemic circulation. Recent reports have suggested GFAP is a dependable marker for auguring subtle disease changes in traumatic brain injury (TBI) and AD. However, pathological anomalies such abnormal structural integrity, cleavage, impaired drainage pathways, and alternative isoforms will lessen its potency and thwarts its ability from becoming a full-fledged and stable biomarker for neurological diseases. Understanding the GFAP biology, including factors that influence its structural integrity and excretory pathways, will be crucial and this review underscores these sections in a succinct manner. Thorough comprehension of GFAP biology is the principal step in unearthing its potential as a powerful marker for auguring disease initiation, and progression in TBI and AD.

Background/Objectives: Peripheral nerve tumours are commonly encountered in clinical practice. Although most are benign, a subset can exhibit aggressive and invasive behaviour, evolving into malignant peripheral nerve sheath tumours (MPNSTs). Due to their rarity and overlapping features with benign lesions, MPNSTs are frequently misdiagnosed during the initial evaluation. Preoperative biopsy may aid in distinguishing malignant from benign lesions. This single-center study aimed to develop and validate a diagnostic algorithm-based on a systematic literature review and institutional case series-to assess the role of preoperative biopsy in the diagnostic workflow. Methods: A systematic review of the literature was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, covering the period from 1998 to 2024. Additionally, a retrospective case series of patients with peripheral nerve lesions treated at the authors' institution between January 2018 and June 2024 was analysed. Results: Forty-eight articles met the inclusion criteria and were categorized into five key domains: radiological features of MPNSTs, associated risk factors and genetic conditions, the role of preoperative biopsy, use of radiotherapy, and general clinical management strategies. The proposed diagnostic algorithm was applied to a series of 36 patients, four of whom met the criteria for preoperative biopsy. In three of these cases, early diagnosis of MPNSTs was achieved. Conclusions: Preoperative biopsy appears to be a safe and cost-effective tool for the early identification of MPNSTs. Early diagnosis may facilitate the use of neoadjuvant therapies-such as radiotherapy or chemotherapy-potentially enabling more radical surgical resection and improving overall patient outcomes.

Background/Objectives: Essential tremor (ET) is the most common movement disorder worldwide. It negatively affects patients' activities of daily living (ADL) and quality of life. Unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy has been proven as a highly effective and safe treatment option for patients with refractory ET. The aims of this study are to explore the effectiveness and safety of tcMRgFUS thalamotomy in patients with ET in a real-world setting. Methods: Patients who underwent tcMRgFUS thalamotomy at the University Hospital of Palermo were prospectively enrolled. Scores obtained by Quality of Life in Essential Tremor Questionnaire (QUEST) and The Essential Tremor Rating Assessment Scale (TETRAS) were compared before and after tcMRgFUS thalamotomy. Predictors of tcMRgFUS thalamotomy effectiveness were explored by multivariable Cox regression analyses. All the adverse events (AEs) during and after the procedure were collected. Results: Fifty patients were included (80% male; median age at tcMRgFUS 67.4 years). After procedure, the QUEST score decreased by 46.2%, while TETRAS-ADL and TETRAS Performance (TETRAS-PE) decreased by 52.2% and 51.8%, respectively. Temperature peak and longitudinal lesion diameter positively correlated with the magnitude of QUEST and TETRAS-PE reduction. A higher baseline TETRAS-PE score predicted a good prognosis (HR = HR 6.6 [95% CI: 2.1-21.3]; p = 0.001). AEs were mild to moderate and transient, while permanent AE was observed only in one case. Conclusions: This real-world study confirms the higher effectiveness and the favorable safety profile of tcMRgFUS thalamotomy in patients with ET by reducing the tremor-related interference in quality of life, disability in ADL, and tremor severity.

Background/objectives: The Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS) predicts neurological outcomes after endovascular thrombectomy (EVT). Given recent expanded indications for EVT, we evaluated CLEOS in a modern cohort of thrombectomy patients.

Methods: We retrospectively analyzed consecutive, anterior circulation EVT patients from January to December 2024 at multiple centers. The primary outcome was a 90-day modified Rankin Scale (mRS) score of 4-6. We compared primary outcome rates between the original CLEOS derivation cohort and the validation cohort. The area under the curve (AUC) was calculated for CLEOS and compared to other prognostic scales.

Results: In the 347 included patients, the mean age was 67.6 (14.9) years, the median National Institutes of Health Stroke Scale (NIHSS) was 15 (10-20), and 137 (42.2%) had a 90-day mRS score of 4-6. A similar proportion of patients in the validation cohort and the derivation cohort achieved the primary outcome (39% each, p = 0.957). The AUC for CLEOS (0.7416, 95% confidence interval [CI] 0.688-0.795) was superior to that of the Pittsburgh Response to Endovascular therapy (AUC 0.681, 95% CI 0.624-0.738, p < 0.01) and Stroke Prognostication using Age and NIHSS (AUC 0.5982, 95% CI 0.556-0.640, p < 0.01), while a trend was observed compared to Houston Intra-Arterial Therapy-2 (AUC 0.6999, 95% CI 0.644-0.756, p = 0.0657) and Totaled Health Risk in Vascular Events (AUC 0.7046, 95% CI 0.560-0.759, p = 0.07). CLEOS ≥ 700 predicted the primary outcome in 16/19 (84.2%) patients.

Conclusions: CLEOS performed well in our modern cohort of thrombectomy patients. Prognostic scales such as CLEOS may be useful in guiding conversations and setting expectations with family members pre- and post-thrombectomy.

Background/Objectives: The onset of autism spectrum disorder (ASD) is thought to be related to fetal testosterone (TSTN) levels or the binding of neurexin (Nrxn) to neuroligin (Nlgn), as per some studies. However, the underlying molecular mechanisms remain unclear. We found that high concentrations of TSTN interrupt Nrxn-Nlgn binding in the neonatal brain, causing impaired social behavior. Methods: We reproduced high concentrations of TSTN in the womb by injecting TSTN into pregnant mice, followed by the quantification of Nrxn-Nlgn binding in the neonatal brain. We also explored the sociability and social novelty preferences of male and female offspring. Results: Nrxn-Nlgn binding in the neonatal brain decreased after TSTN injection. Furthermore, male mice showed impairment in social novelty, whereas female mice showed impairments in both social novelty and sociability following TSTN injection. Conclusions: This study revealed that high concentrations of TSTN during brain development interrupted Nrxn-Nlgn binding and led to impairments in social behavior.

Background/Objectives: Psychotic disorders with childhood or adolescent onset pose major therapeutic challenges due to their complex etiology and variable treatment response. While pharmacogenetics and neuroimaging biomarkers have independently shown potential for guiding therapy, their combined utility remains underexplored. This study aimed to investigate whether integrating CYP2D6 pharmacogenetic profiles with structural neuroimaging findings can enhance personalized treatment and predict clinical outcomes in pediatric psychotic disorders. Methods: This prospective observational study included 63 children and adolescents (10-18 years) with DSM-5 diagnosed psychotic disorders. All patients underwent baseline MRI and standardized clinical assessments (PANSS, CGI, GAF). CYP2D6 genotyping was performed in 31 patients (49.2%), categorizing them as extensive (EMs) or intermediate metabolizers (IMs). Patients were treated with atypical antipsychotics and followed for 18 months. Outcomes included symptom severity, global functioning, and side-effect profiles. Results: EM patients demonstrated superior clinical improvement, as evidenced by a reduction in PANSS scores (from 118 to 40) and a corresponding increase in GAF scores (from 39 to 76), compared to the IM and non-tested groups. IM patients exhibited a higher prevalence of MRI abnormalities and slower response. Significant correlations emerged between CYP2D6 genotype, MRI findings, and treatment outcomes (p < 0.001). Combined biomarker profiles enhanced the prediction of therapeutic response and tolerability. Conclusions: Integrating CYP2D6 pharmacogenetic data with neuroimaging biomarkers provides valuable guidance for personalizing antipsychotic treatment in pediatric psychosis. This approach improves clinical outcomes and reduces adverse effects. Future research should further explore the integration of multimodal biomarkers in larger, longitudinal cohorts to optimize individualized psychiatric care for this vulnerable population.