Acta neurologica Belgica最新文献

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease identified by progressive motor neuron loss. NLRP3 inflammasomes induce inflammation and pyroptosis, which can lead to neurodegeneration, muscle atrophy, and respiratory decline. miR-223 targets NLRP3 and suppresses inflammasome formation. Here, miR-223, NLRP3 and IL-1β levels were evaluated as plasma biomarkers in the incidence and progression of ALS.

Methods: 32 ALS patients and 32 healthy subjects were assessed. In all patients, the functional disability was determined by Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the respiratory dysfunction was assessed by the percent predicted forced vital capacity (ppFVC) index in spirometry examination. Plasma levels of miR-223, NLRP3 and IL-1β were assessed in ALS and control groups.

Results: Compared to the healthy controls, ALS patients showed decreased miR-223 expression (P < 0.0001), increased NLRP3 expression (P = 0.0002) and increased IL-1β level (P = 0.0003). The areas under the ROC curves for miR-223, NLRP3 and IL-1β were 0.82, 0.76 and 0.75 respectively. The ALSFRS-R and ppFVC values were positively correlated with miR-223 and negatively correlated with NLRP3 and IL-1β levels.

Conclusion: Our results indicated that changes in miR-223, NLRP3 and IL-1β levels may correlate with the occurrence and functional progression of ALS. Additionally, therapeutic approaches based on miR-223 and inflammatory mediators can be proposed as effective strategies against disease progression.

Background: Hospitalized patients with dementia exhibit high mortality rates, underscoring the importance of investigating variables associated with reduced survival. This study aims to determine the incidence of dementia among hospitalized patients and survival rates at 1 and 3 years post-hospitalization.

Methods: A retrospective cohort study was conducted using administrative databases from the Ministry of Health of Colombia. One- and three-year survival rates, along with adjusted hazard ratios for survival accounting for comorbidities included in the Charlson Index, were assessed using a Cox proportional hazards model. This analysis was performed for patients with dementia versus a control group without dementia. Additionally, findings were compared with those from an inverse propensity score weighting model.

Results: 6.769 (1.04%) patients were diagnosed with dementia, and 5798 (85.65%) were over 65 years of age. The unadjusted HR, the HR adjusted using the proportional hazards Cox model, and the HR obtained through propensity score matching (PSM) were 10.32 (95% CI 9.82 to 10.84), 1.69 (95% CI 1.60 to 1.78), and 1.32 (95% CI 1.02 to 1.71), respectively. The 1-year adjusted mortality rates for patients with dementia and those without were 12.5% and 1.31%, respectively, while the corresponding 3-year adjusted mortality rates were 21.25% and 2.76%. Through PSM, we determined that the mean survival time for patients with dementia, in comparison to those without, was - 0.98 months (95% CI: -0.65 to -1.94; p < 0.001).

Conclusions: Dementia significantly reduces survival rates of hospitalized patients, regardless of other comorbidities. Specifically, our research revealed that dementia was associated with a decrease in 3-year survival by an average of 0.98 months.

Background: Copper deficiency peripheral neuropathy caused by excessive treatment in Wilson's disease has been reported. But its pathological characteristics are rarely reported. Here, we report a case of copper deficiency peripheral neuropathy in Wilson's disease and present the characteristics of its nerve biopsy.

Case description: A 44-year-old female patient diagnosed with Wilson's disease was on long-term oral administration of zinc gluconate and copper chelators. In June 2022, she developed symptoms of peripheral neuropathy, accompanied by anemia and neutropenia. The 24-hour urinary copper excretion was 53.85 µg. Serum copper was 66.6 µg/L, and ceruloplasmin was 0.01 g/L. Electromyography showed length-dependent axonal damage in peripheral nerves. Sural nerve biopsy showed mainly axonal damage and decreased density of nerve fibres of all classes (large and small myelinated and unmyelinated), accompanied by demyelination. Ultimately, the diagnosis of copper deficiency peripheral neuropathy caused by excessive treatment of Wilson's disease was established. After discontinuing copper chelation therapy, she experienced mild alleviation of symptoms.

Conclusion: The pathological features of copper deficiency peripheral neuropathy in Wilson's disease include the formation of axonal vacuoles, the presence of myelin ovoids, and a reduced number of large and small myelinated and unmyelinated nerve fibers. This case emphasizes the importance of monitoring copper metabolism during the stable phase of treatment for patients with Wilson's disease.

Background: Cognitive impairment (CI) frequently occurs in relapsing-remitting multiple sclerosis (RRMS) and is assumed to be irreversible. Recent longitudinal studies highlighted the heterogeneity of CI in RRMS, challenging the traditional view of inevitable progression. Longitudinal studies exploring the baseline determinants of future cognitive decline are limited, and none yet explored the predictive value of patient-reported outcome measures (PROMs).

Objective: To explore the evolutionary patterns of cognitive status in a cohort of RRMS patients initiating a new disease modifying treatment, and to determine whether PROMs may have a predictive value for future cognitive decline.

Methods: This prospective study is a 36-month follow-up of 59 RRMS patients who underwent yearly a comprehensive, multiparametric assessment combining clinical, neuropsychological, MRI-derived metrics and a set of self-reported questionnaires. Lesion load and brain volumes were analyzed and processed by the automated MSmetrix^® software (Icometrix^®, Leuven, Belgium). A longitudinal logistic regression analysis was performed to investigate baseline predictors of future cognitive decline.

Results: A total of 33 (56%) and 17 (35%) patients were defined as cognitively impaired at baseline and at the end of the study, respectively. Of these 33 patients, 20 showed either improvement and/or impairment in fewer cognitive domains at 36-month follow-up. Baseline physical disability as measured by EDSS was the best predictor for future cognitive decline (OR: 2.17; p = 0.03, 95% confidence interval = 1.07-4.38). None of the PROMs variables contributed to predict further cognitive decline.

Conclusions: Our findings highlight the importance of considering the evolution of CI in MS as a dynamic phenomenon with a substantial heterogeneity.

Objectives: To evaluate clinical and radiological features, risk factors, etiology, treatment approaches, and outcomes of pediatric arterial ischemic stroke (AIS) and cerebral sinovenous thrombosis (CSVT).

Methods: Children beyond the neonatal period diagnosed with AIS or CSVT between 2002 and 2017 were retrospectively analyzed. Demographics, clinical presentations, radiological findings, risk factors, etiologies, treatments, and outcomes were reviewed.

Results: A total of 94 patients with AIS and 27 with CSVT were included. The median age for AIS patients was 4.1 years (IQR:1.6-9.8). Focal neurological deficits were present in 81.7%, hemiparesis being the most common symptom. Seizures were noted in 30.4%. Cardiac abnormalities (39%) and arteriopathies (38%) were the most common etiologies, with prothrombotic conditions and rare genetic disorders also remarkable underlying risk groups. Antithrombotic therapy was administered without major complications to 89.3%. At a median three-year follow-up, 33.8% had no neurological deficits, 33.8% had moderate to severe deficits or died, 16.2% had epilepsy. For CSVT, the median age was 9.6 years (IQR:3.2-12.6). Diffuse neurological symptoms were present in 77.7%, primarily headaches and vomiting. Seizures occurred in 22.2%. All CSVT patients had at least one risk factor. Chronic systemic conditions (63%) and infections (44%) were the most common risk factors. During follow-up of a median of 43 months, 63.6% had no neurological deficits.

Conclusions: Pediatric stroke has a broad spectrum of risk factors. Our study contributes to the existing knowledge on pediatric AIS and CSVT, providing a detailed overview of pediatric AIS and CSVT at a tertiary center, reflecting the growing awareness of physicians in childhood cerebrovascular diseases.

PHARC syndrome is an autosomal recessive neurodegenerative disease caused by mutations in the ABHD12 gene and is characterized by five main clinical features: polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts. This systematic review aimed to characterize the neurological features of PHARC syndrome and identify potential new clinical features. A systematic search of studies reporting cases of PHARC syndrome was conducted using PubMed/MEDLINE and NLM databases, identifying 57 unique cases. The results showed that hearing loss was the most common initial symptom, with a complete syndrome observed in only 31.6% of reported cases. The mean diagnostic delay from the appearance of the first PHARC-related symptom to diagnosis was 20.5 years. Although pyramidal signs are not classically associated with PHARC syndrome, they were a prevalent feature when assessed. Patients with pyramidal signs were more likely to exhibit an ataxic phenotype (p-value 0.018), a complete syndrome (p-value 0.092), and cerebellar atrophy on MRI (p-value 0.001), compared to those without pyramidal signs. This review further supports the highly variable phenotype of PHARC syndrome and the lack of a clear genotype-phenotype correlation. Further research is needed to clarify the relevance of these findings within the clinical spectrum of PHARC syndrome.

Background: Despite the close association of Alzheimer's disease (AD) with muscle decline, the biomarkers of age-related muscle loss, termed sarcopenia, in AD remain elusive.

Objectives: We investigated the plasma neurofilament light (NfL) chain levels as potential biomarkers of sarcopenia in AD patients. DESIGN SETTING, PARTICIPANTS, MEASUREMENTS: We conducted a cross-sectional, observational study on older adults, including controls and patients with AD (n = 38-44/group). We measured the frequency of sarcopenia, body composition, handgrip strength (HGS), gait speed, and short physical performance battery (SPPB) in the study participants. We also measured the plasma NfL levels as marker of neurodegeneration.

Results: AD was associated with a higher frequency of sarcopenia and reduced HGS, gait speed, and SPPB scores (all p < 0.05). The higher plasma NfL levels in AD patients were correlated with lower HGS, gait speed, and SPPB scores (all p < 0.05). Plasma NfL exhibited moderate accuracy in diagnosing sarcopenia (area under the curve; AUC = 0.701, p < 0.001) and functional dependency (AUC = 0.772, p < 0.001). Among different subgroups of AD, moderate AD was associated with more advanced sarcopenia and functional dependency than early and mild AD. Patients with AD also exhibited heightened inflammation and oxidative stress.

Conclusion: Altogether, plasma NfL may be a preliminary tool in diagnosing advanced sarcopenia and functional dependency in AD. The study is relevant to non-ambulant and/or comatose AD patients with sarcopenia.

Objectives: Traumatic brain injury (TBI) is a critical public health issue with high mortality and disability rates. Current diagnostic tools lack sensitivity and specificity, under-scoring the need for novel biomarkers. This study aimed to evaluate the clinical utility of NLRP3, ASC, and Caspase-1 as biomarkers for assessing TBI severity and prognosis.

Methods: A prospective cohort of 89 patients with moderate-to-severe TBI was studied. Blood and cerebrospinal fluid (CSF) samples were collected for four consecutive days post-injury. Levels of NLRP3, ASC, and Caspase-1 were measured using enzyme-linked immunosorbent as-say (ELISA). Statistical analyses, including ROC curve analysis, were conducted to assess their predictive performance.

Results: NLRP3, ASC, and Caspase-1 levels in both serum and CSF were significantly elevated in TBI patients, with higher levels correlating with greater injury severity. ROC analysis revealed that CSF biomarkers, particularly NLRP3, demonstrated superior predictive value. CSF NLRP3 levels on days 1, 2, and 4 had AUC values of 0.9871, 0.9466, and 0.8967, respectively. Dynamic changes in these biomarkers over time provided insights into disease progression and prognosis. Serum markers, while less predictive than CSF, were also effective for assessing injury severity.

Conclusions: NLRP3, ASC, and Caspase-1 are promising biomarkers for evaluating TBI severity and predicting outcomes. Their dynamic monitoring may improve clinical management and in-form therapeutic strategies. Future research should validate these findings in larger cohorts and explore interventions targeting these inflammatory pathways.

Background: Essential tremor (ET) is a common neurological disorder that significantly impacts daily activities. This meta-analysis aims to evaluate the safety and efficacy of cerebellar repetitive Transcranial Magnetic Stimulation (rTMS) and cerebellar Theta Burst Stimulation (TBS) in treating ET.

Methods: We searched through June 14, 2024, four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL) to identify clinical trials investigating cerebellar rTMS or TBS in ET patients. Eligibility criteria included clinical trials reporting on safety and efficacy outcomes. Six reviewers screened and extracted data independently, resolving conflicts through consensus. Risk of bias was assessed. Statistical analyses involved pooling continuous outcomes using the mean difference (MD) and 95% confidence intervals (CI) with RevMan 5.3.

Results: Out of 201 screened studies, nine studies were included, with a total of 261 participants (149 received rTMS, 112 were in control groups). The meta-analysis revealed no statistically significant difference between rTMS and sham groups for Fahn-Tolosa-Marin (FTM) subscores A (MD: -3.03, 95% CI: [-7.66, 1.60], P = 0.20), B (MD: -2.74, 95% CI: [-8.09, 2.61], P = 0.32), C (MD: -1.57, 95% CI: [-5.12, 1.97], P = 0.38), and FTM-Total (MD: -8.12, 95% CI: [-20.47, 4.23], P = 0.20). Sensitivity analysis confirmed these results. Adverse events were minimal: headaches (1/44 rTMS, 2/19 sham), dizziness (1/44 rTMS, 0/19 sham), and no reported seizures or syncope.

Conclusion: While individual studies noted significant FTM score improvements post-rTMS treatment, the pooled analysis found no significant differences versus sham. Further research with standardized protocols and larger samples is required to optimize rTMS use for ET.