Neurological Sciences最新文献

Background: The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production.

Method: Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aβ production in COS cells transfected with wild-type or mutant PSEN1.

Results: The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aβ42 in PSEN1 G266S-transfected cells significantly increased.

Conclusion: Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

Introduction: Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system. Fatigue represents one of the most prevalent and limiting symptoms of MS, and is associated with vascular dysfunction, notably increased arterial stiffness.

Objective: This study examined the relationship between arterial stiffness and perceived fatigue in persons with MS.

Methods: The sample of 52 persons with MS (71.2% Female; Age: 46.7 ± 12.3 yrs.) completed arterial stiffness and fatigue assessments as baseline for an exercise training intervention. Applanation tonometry measured arterial stiffness, pulsatility and waveform characteristics, and yielded the following outcomes: carotid-femoral pulse wave velocity (cfPWV), carotid pulse-pressure (cPP), and aortic augmentation pressure (AP). Perceived fatigue was measured using the Fatigue Severity Scale (FSS).

Results: The mean (SD) scores for cfPWV, cPP, and AP were 7.0 ± 1.8 m/s, 35.7 ± 8.8 mmHg, 8.2 ± 6.2 mmHg, respectively. The mean (SD) FSS score was 4.6 ± 1.4 and indicated elevated fatigue. There were statistically significant (p < .05) inverse correlations between cfPWV (r = -.32), cPP (r = -.37) and AP (r = -.32) with FSS scores, and the correlations remained significant even after controlling for disability, body mass index, age, and sex.

Conclusion: Our results indicate a consistent pattern of inverse relationships between arterial stiffness, pulsatility, and waveforms with fatigue independent of disability, body mass index, age, and sex in MS. This could be explained by lower sympathetic activation linking higher arterial stiffness, pulsatility and augmentation pressure with lower fatigue in persons with MS.

Background: Rett syndrome (RTT) is an uncommon inherited neurodevelopmental disorder that affects brain development, mostly in females. It results from mutation in MECP2 gene in the long arm (q) of the X chromosome.

Objective: Trofinetide is a recently developed drug that has a neuroprotective effect on neurons, and it is our aim in this meta-analysis to evaluate its efficacy and safety in treating Rett syndrome patients.

Methods: We searched 5 databases (PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases) to identify randomized controlled trials (RCTs) comparing Trofinetide and placebo in patients with Rett syndrome until August 13, 2023.Our primary outcomes were the Clinical Global Impression-Improvement (CGI) and the Rett syndrome Behavior Questionnaire (RSBQ). We used Risk of Bias Assessment tool-2 (ROB2) to assess the methodological quality of the included randomized controlled trials.

Results: Three RCTs with a total of 325 patients were included with a follow-up duration ranging from one month to three months. 186 patients received the intervention drug (Trofinetide) and 138 received the placebo. Trofinetide was found to reduce CGI and RSBQ significantly more than placebo (MD = -0.35, 95% CI [-0.52 to -0.18], P 0.0001), (MD = -3.40, 95% CI [-3.69 to -3.12], P 0.00001) respectively. Most adverse events did not show any statistical difference between Trofinetide and the placebo.

Conclusion: Trofinetide offers promise as a potential effective and safe therapeutic opportunity for a population without many available treatments, with improvements seen on both CGI and RSBQ assessments and no severe adverse effects reported.

The present work investigates whether financial abilities can be associated with numerical abilities and with general cognitive abilities. We compared performance on numerical and financial tests, and on tests routinely used to measure general cognitive performance, in healthy controls and in a group of people with heterogeneous pathological conditions including mild cognitive impairment, amyotrophic lateral sclerosis, traumatic brain injury, and schizophrenia. Patients showed lower performances in both numerical and financial abilities compared to controls. Numerical and financial skills were positively correlated in both groups, but they correlated poorly with measures of general cognitive functioning. Crucially, only basic financial tasks -such as counting currencies- but not advanced ones -like financial judgments- were associated with numerical or general cognitive functioning in logistic regression analyses. Conversely, advanced financial abilities, but not basic ones, were associated with abstract reasoning. At a qualitative analysis, we found that deficits in numerical and financial abilities might double dissociate. Similarly, we observed double dissociations between difficulties in financial abilities and cognitive deficits. In conclusion, financial abilities may be independent of numerical skills, and financial deficits are not always related to the presence of cognitive difficulties. These findings are important for both clinical and legal practice.

Parkinson's disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer's disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients' quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD.

Background: Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an ASPECTs ≥ 6. Recent randomized controlled trials (RCTs) have become available on effect of EVT in patients with LVO-related large core infarct stroke (ASPECTS 0-5). We conducted a systematic review and meta-analysis of trials on patients with large core infarct treated with thrombectomy compared to best medical therapy (BMT).

Methods: The study followed PRISMA guidelines. Primary endpoint was functional independence at 90 days (modified Rankin Scale mRS < 3). Secondary endpoints were 3-month moderate disability (mRS < 4), excellent outcome (mRS < 2) and change in mRS (shift analysis). Safety outcomes were: symptomatic intracranial hemorrhage (sICH) and 3-month mortality.

Results: Seven RCTs were included with a total of 1964 patients. Functional independence was significantly more frequent in EVT vs BMT group (19.4% vs 8%; OR = 2.72, 95%CI = 2.06-3.61, p_{heterogeneity} = 0.08; I2: 47%). Moderate outcome was also more prevalent in EVT group (OR = 2.00; 95%CI = 1.61 - 2.48, p_{heterogeneity} = 0.17; I2: 46%) as well as excellent outcome (OR: 1.54, 95%CI = 1.07 - 2.22, p_{heterogeneity} = 0.13; I2: 40%). Shift analysis was also significant with OR 1.59 (CI = 1.33-1.82 and p < 0.001). Finally sICH, that occurred in 68 patients, was more frequent in EVT (OR = 1.63, 95%CI = 0.99 - 2.69, p_{heterogeneity} = 0.68; I2: 0%) while 3 m mortality was reduced in EVT (31% vs 37,1%, OR 0.76 CI = 0.62-0.92).

Conclusions: This updated pooled data show that, in LVO-stroke patients with a large core infarct, EVT plus BMT (as compared to BMT alone) increases significantly the chances of achieving a good functional outcome at 90 days and reduces the 3- month mortality despite a marginal increase in acute sICH.

Objective: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive loss of motor neurons. It is a growing and underestimated disease, prompting this epidemiological study to describe the characteristics of ALS in Egyptian patients.

Methods: This is a prospective hospital based study. ALS patients were recruited consecutively from Neuromuscular Unit in Ain Shams university Hospital from December 2018 to June 2023. Demographic data and disease related parameters were recorded.

Results: 203 ALS patients had a mean age of onset equal 39 years and an inter quartile range IQR of (28.00-51.00). 76% of the cases were spinal onset ALS. Median disease duration was 2 years with IQR of (1-4 years); male to female ratio was 2.5:1; 18% of patients were familial ALS (FALS), while 19% were Juvenile ALS (JALS). Median diagnostic delay was 12 ± (6-36) months. Median Amyotrophic Lateral Sclerosis Functional Rating Scale Revised scores (ALSFRS-R) at presentation was 34.5 IQR of (26.00-40.00). Also, the mean rate of disease progression ALSFRS-R decline [points/month] was 0.76 ± 0.51.

Conclusion: Our cohort was characterized by a younger age of onset, male predominance, more familial cases, within average Initial ALSFRS-R scores as well as diagnostic delay. Juvenile ALS patients were much more common in our population. These findings suggest an influential presence of genetic and epigenetic factors affecting the clinical phenotype of Egyptian ALS patients.

Background: Excessive daytime sleepiness (EDS) and freezing of gait (FOG) are prevalent non-motor and motor symptoms in patients with Parkinson's disease (PD), significantly impacting their quality of life. However, the correlation between EDS and FOG progression in de novo PD patients remains controversial.

Methods: A total of 328 participants from the Parkinson's Progression Markers Initiative (PPMI) were divided into two groups: 43 with EDS (EDS group) and 285 without EDS (nEDS group). The cumulative incidence of FOG was assessed at the 5-year follow-up using Kaplan-Meier and log-rank tests. Multivariate Cox proportional hazards models were used to assess the impact of EDS on FOG progression in PD patients, with validation for robustness through sensitivity and subgroup analyses.

Results: The EDS group experienced a higher incidence of FOG throughout the 5-year follow-up than did the nEDS group. Multivariate Cox proportional hazards models showed significantly association between EDS severity and enhanced risk of developing FOG (HR = 1.076, 95% CI:1.007 ~ 1.149, P = 0.031). For sensitivity analysis, parallel analyses were performed by substituting the independent variable with categorical variables, which yielded analogous outcomes (HR = 1.837, 95% CI:1.063 ~ 3.174, P = 0.029). Furthermore, subgroup analyses based on sex, age, TD/PIGD classification, depressive symptoms, cognitive impairment, mean caudate nucleus uptake level, mean putamen nucleus uptake level and CSF Aβ-42 level revealed no significant interactions between subgroups (all P values for interaction were > 0.05).

Conclusion: EDS is a potential prognosis factor for the progression of FOG in patients with PD.

Background: Cognitive deficits are common nonmotor symptoms in Parkinson's disease (PD). Non-Invasive Brain Stimulation (NIBS) could be a potential aid to prevent or delay dementia progression in this clinical population. However, previous studies reported controversial results concerning their efficacy on cognitive symptoms of PD. Hence, the present meta-analysis aims to systematically examine the effects of NIBS as possible treatments for PD cognitive impairments. Understanding NIBS' impact on these symptoms may be of outstanding importance to implement new therapeutic strategies and improve the patients' quality of life.

Methods: EMBASE, Scopus, and PubMed databases were systematically searched for consecutive studies published from 2000 to March 2023 describing Randomized Controlled Trials studies evaluating the effect of NIBS on PD cognitive symptoms. From the included studies, data concerning neuropsychological tests were extracted and grouped into six cognitive domains, separately analyzed. Hedge's method was computed as the effect size measure of the extracted data; heterogeneity among studies and publication bias were also assessed. The Cochrane's RoB2 tool was used to evaluate the risk of bias for each of the included studies.

Results: After database searching and screening of texts, sixteen studies met the inclusion criteria. No significant results emerged from any investigated cognitive domain when comparing NIBS and sham treatments.

Conclusion: Several factors may have contributed to the lack of effects; among these, methodological choices, the small sample of studies, the high heterogeneity of data and stimulation protocols pose the need for more controlled studies to highlight the potentiality of NIBS as a future treatment for PD cognitive impairments.