Journal of Neurology最新文献

Background and objectives: The phenotype of p.A53T-α-synuclein (SNCA) mutation carriers with Parkinson's disease (A53T-PD) appears more severe compared to idiopathic PD (iPD), however, information is limited. Here we conducted a comprehensive longitudinal study to investigate the progression of motor and nonmotor features of Α53Τ-PD compared to iPD.

Methods: Detailed longitudinal 3-year data, concerning both motor and non-motor features, of 16 p.A53T-PD and 48 iPD, matched for age (51-53 years) and disease duration (approximately 4 years) at baseline, were downloaded from the Parkinson's Progression Markers Initiative (PPMI) database and compared between the two groups. Additionally, a cognitive composite score was generated by five cognitive tests, focused more on executive/visuospatial function.

Results: At baseline, global cognitive function, as assessed by the Montreal Cognitive Assessment (MOCA), was not significantly different between the two groups, in contrast to tests evaluating executive/visuospatial function, including the composite score, which were worse in A53T-PD. There was a significant decline over time in all neuropsychological tests in A53T-PD, while iPD remained stable. A similar pattern was revealed for motor status and function, as well as autonomic function, which were similar between the two groups at baseline, but deteriorated significantly only in A53T-PD over time.

Discussion: A53T-PD patients present an accelerated decline in both motor and non-motor parameters, with an impairment in executive-visuospatial function occurring early in the disease process. Such data may set the stage for targeted disease-modifying therapies in this particular subtype, while generated data may be widely applicable to iPD, which is largely a sporadic synucleinopathy.

Background: Cognitive impairment is a core feature of Huntington's disease (HD), yet no disease-modifying or symptomatic interventions have demonstrated efficacy in addressing these deficits. Non-pharmacological interventions, particularly cognitive training (CT), are promising options for maintaining neural plasticity, enhancing cognition, and improving emotional well-being.

Methods: This 24-week, single-center, randomized, single-blind study evaluated the safety and efficacy of two cognitive rehabilitation strategies in early-to-middle-stage HD patients. Participants were randomized into a computerized cognitive training (CT; n = 13) intervention or a music therapy (MT; n = 16) intervention. A standard of care (SoC; n = 15) group with no active intervention was also involved. Weekly 45-min sessions were conducted. Baseline and endpoint assessments included measures of global cognition, functional, motor, and neuropsychiatric assessments, along with structural and functional neuroimaging.

Results: Both CT and MT groups demonstrated significant improvements in primary and secondary cognitive endpoints, including global cognition an composite measures of disease severity. Regression analysis identified longitudinal cognitive score changes as independent predictors of the rate of atrophy in the caudate, putamen, and inferior frontal gyrus. Functional connectivity analysis showed distinct intervention-related effects: CT group exhibited increased connectivity between the central executive and sensorymotor networks, while MT group reduced aberrant connectivity between the central executive and the default-mode network.

Conclusion: This is the first randomized-controlled trial to evaluate two cognitive rehabilitation strategies in HD using multimodal neuroimaging. Both interventions were effective in improving cognition and modulating structural and functional brain changes in regions critical to HD. Trial Registration ClinicalTrials.gov (ID: NCT05769972).

Background: Up to 80% of intensive care unit (ICU) patients suffer from neuromuscular disorders like critical illness polyneuropathy/myopathy (CIP/CIM), requiring further rehabilitation.

Objective: This study investigates differences in the clinical course between Coronavirus Disease 2019 (COVID-19) and non-COVID-19 patients with CIP/CIM undergoing post-acute neurological rehabilitation (PANR) and the impact of COVID-19 on rehabilitation outcomes.

Methods: A multicenter observational study was conducted in nine German PANR facilities. The clinical course and outcome were compared between COVID-19 and non-COVID-19 patients at rehabilitation admission and discharge. Functional outcomes were measured with the modified Ranking Scale (mRS) and the Barthel Index (BI). Functional independence was defined as either mRS Score < 3 or BI > 75 at discharge, discharged home without nursing support with a BI > 65, or discharged to further rehabilitation (phase D). To analyze outcome predictors, Cox regression was used.

Results: A total of 323 patients (COVID-19 n = 166) after an ICU stay were enrolled, and outcome measures were available for 298. 56 of them achieved functional independence at discharge. COVID-19 patients had better functional scores at admission and discharge and a shorter length of stay as the non-COVID group. Pre-existing diabetes was significantly negatively associated with functioning at discharge.

Conclusions: This analysis provides the first evidence for differences and predictors of the clinical course and outcome for COVID-19 and non-COVID-19 patients with CIP/CIM in the phase of post-acute rehabilitation. Our results offer valuable impulses for rehabilitation strategies for these patients. https://drks.de/search/de , German Clinical Trials Register, ID DRKS00022845, registered on September 1, 2020.

Background: The underlying etiologies responsible for persistent geotropic nystagmus (PGN) and apogeotropic nystagmus (PAGN) remain elusive. In this study, we analyzed the symptoms of patients with PGN and PAGN and categorize them based on diagnostic criteria for established vestibular disorders.

Methods: Clinical signs, recurrences, and duration of vestibular symptoms in patients with PGN or PAGN were collated and included auditory, neurologic, and migrainous symptoms as well as migraine history. Patients were then reclassified into unique etiological groups according to the established diagnostic criteria for vestibular disorders.

Results: Among 428 patients with nystagmus, 57 (13.3%) presented with PGN or PAGN. Of the 56 patients included in the study, 50 (89.3%) experienced a recurrence of vertigo or dizziness, and 28 (50%) had more than five episodes. Regarding the duration of symptoms, 32 patients (57.1%) experienced vestibular episodes lasting ≤ 1 day, and 46 patients (82.1%) had episodes lasting ≤ 1 week. Based on the available and accepted diagnostic categorization, 17 patients (30.4%) were diagnosed with vestibular migraine, 15 (26.8%) with probable vestibular migraine, 15 (26.8%) with benign recurrent vertigo, 3 (5.4%) with cerebellar lesions, 1 (1.8%) with sudden sensorineural hearing loss, and 5 (8.9%) with undetermined diagnoses.

Conclusions: While PGN and PAGN can be caused by various vestibular disorders, our data support the majority of cases are episodic and linked to the pathophysiology of vestibular migraine.

Discrepancies in results between cerebrospinal fluid (CSF) 14-3-3 protein and prion protein detection using real-time quaking-induced conversion (RT-QuIC) might limit the confidence in ante-mortem clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). We aimed to evaluate the concordance and diagnostic performance of 14-3-3 protein and RT-QuIC in a real clinical practice cohort, and to analyze neuronal/glial damage biomarkers in sCJD patients based on their diagnostic assay results. A retrospective multicentre study was conducted on 157 suspected sCJD patients from 38 Spanish hospitals in a 4-year period. CSF 14-3-3 protein and RT-QuIC were simultaneously evaluated in a single laboratory. A diagnosis of probable sCJD was established in 63 patients (40.1%), of which 12 (19.0%) were ultimately diagnosed with definite sCJD. Forty-one sCJD patients (65.1%) were positive for both 14-3-3 protein and RT-QuIC, 17 (27.0%) isolated positive for RT-QuIC, and 5 (7.9%) isolated positive for 14-3-3 protein. RT-QuIC demonstrated higher sensitivity (92.1%) and specificity (98.9%) compared to 14-3-3 (73.0% and 62.8%) for the diagnosis of sCJD. Isolated RT-QuIC positivity was associated with longer disease duration (median: 10.5 months, IQR: 8.8-15.7), higher frequency of Met/Val cases (75.0%), lower prevalence of periodic sharp-wave complexes (5.9%), and lower levels of GFAP (3967.4 pg/mL), UCH-L1 (2218.1 pg/mL), and t-Tau (228.8 pg/mL) compared to double-positive and isolated 14-3-3-positive patients. In conclusion, CSF RT-QuIC is a highly specific and sensitive biomarker for ante-mortem sCJD diagnosis and should be considered as the preferred CSF ancillary test. Isolated RT-QuIC positivity indicates a less aggressive biological disease in sCJD patients.

Rituximab (RTX) is a monoclonal antibody targeting the B-cell CD20 surface antigen used as a prophylactic treatment for Aquaporin 4-immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD). However, a consensus regarding dosage and maintenance intervals is lacking, and the effects of regular/irregular use on disease recurrence and prognosis, and the risk factors associated with clinical relapse, remain unclear. Therefore, we investigated the efficacy/safety of regular RTX use in patients with NMOSD, and explored risk factors associated with clinical relapses. Data from 106 patients with NMOSD were retrospectively collected from January 5, 2016, and March 1, 2023. Patients were categorized as regular/irregular RTX use, with the latter defined by two intervals of > 9 months, or a single interval of > 12 months, without B-cell monitoring. Compared to the regular treatment group, irregular treatment group showed significant higher annual recurrence rate (ARR) (p = 0.033), Expanded Disability Status Scale (EDSS) score (p = 0.041), and proportions of severe relapse (p = 0.006). In regular RTX use group, the cumulative relapse risk after RTX treatment was significantly lower (p < 0.001). When only considering relapses occurring more than 1 month after starting RTX treatment, 82.3% (51/62) of AQP4-IgG + NMOSD were relapse-free. Independent risk factors of relapse included serum AQP4-IgG titer ≥ 320 at initial disease onset, and severe demyelinating episodes in the first attack. There were no severe side effects. Regular RTX treatment significantly reduces the ARR, incidence of severe relapse, and disability risk in patients with NMOSD.

Visual hallucinations in individuals following sight loss (Charles Bonnet syndrome; CBS) have been posited to arise because of spontaneous, compensatory, neural activity in the visual cortex following sensory input loss from the eyes-known as deafferentation. However, neurophysiological investigations of CBS remain limited. We performed a multi-modal investigation comparing visual cortical activity in 19 people with eye disease who experience visual hallucinations (CBS) with 18 people with eye disease without hallucinations (ED-Controls; matched for age and visual acuity) utilising functional MRI, EEG, and transcranial magnetic stimulation (TMS). A pattern of altered visual cortical activity in people with CBS was noted across investigations. Reduced BOLD activation in ventral extrastriate and primary visual cortex, and reduced EEG alpha-reactivity in response to visual stimulation was observed in CBS compared to ED-Controls. The CBS group also demonstrated a shift towards lower frequency band oscillations in the EEG, indicative of cortical slowing, with significantly greater occipital theta power compared to ED-controls. Furthermore, a significant association between reduced activation in response to visual stimulation and increased excitability (in the form of reduced TMS phosphene thresholds) was observed in CBS, indicating persistent visual cortical activation consistent with hyperexcitability, which was found to be significantly associated with increased hallucination severity. These results provide converging lines of evidence to support the role of increased visual cortical excitability in the formation of visual hallucinations in some people following sight loss, consistent with the deafferentation hypothesis.