Journal of Neurology最新文献

Aim: As part of the development of a smartphone-based app for monitoring MS disease activity and progression (dreaMS, NCT05009160), we developed six gamified tests with multiple difficulty levels as a monitoring tool for cognition. This study quantified the relative difficulty between levels and investigated their reliability, ability to depict practice effects, and user acceptance.

Methods: Healthy volunteers played each game, covering five cognitive domains, twice per day for 11 consecutive days. Linear mixed models determined the relative difficulty of the levels. Spearman's correlation of the two daily repetitions measured test-retest reliability. Difficulty increased daily except for days 2, 6, and 11, when the easiest level ("Beginner") was repeated to estimate practice effects. Participants rated enjoyment and other components of acceptance on a 5-point scale.

Results: We included 82 participants from April to July 2023 in Basel, Switzerland, of which 76 (51 female, age: 40.3 ± 13.9 years, range 18-69) completed the study according to protocol. Generally, mean performances decreased with higher difficulty levels. Across all levels of all games, the median test-retest correlation was 0.825 (range of medians 0.55-0.9). Mean performance in level "Beginner" improved across all games. The mean enjoyment rating was 3.9 (range: 3.1-4.3).

Conclusion: Our study showed that the CoGames yield reliable measures across different cognitive domains and difficulty levels and were enjoyable to play. The observed practice effects must be considered, but also indicate sensitivity to change. These results support the hypothesis that adaptive gamified digital tests can serve as a reliable and well-accepted monitoring tool of cognition in PwMS.

Cerebral vasculitis is a rare but severe manifestation of neurosarcoidosis (NS) that has received little attention. The aim of the present study was to characterize clinical and diagnostic features as well as potential treatment strategies of cerebral vasculitis related to NS. We assessed 29 patients with cerebral vasculitis related to NS (15 female, mean age at time of diagnosis 45 years, SD = 11.85) among these were four new cases from our hospital records and 25 previously published cases from a systematic literature review. The demographic, clinical, and diagnostic features of those 29 patients with cerebral vasculitis related to NS were compared with a group of 73 NS patients without vasculitic involvement (37 female, mean age at time of diagnosis 47 years, SD = 14.79). Neurologic deficits and MRI abnormalities were significantly more frequent in cerebral vasculitis related to NS than in NS without vasculitic involvement. Patients with cerebral vasculitis related to NS significantly more often presented with headache, motor symptoms, and cognitive and/or behavioral changes. Non-neurologic manifestations of sarcoidosis did not significantly differ in character or frequency between both groups. Glucocorticoids in combination with methotrexate, cyclophosphamide, or infliximab were the most frequently used treatment strategies in cerebral vasculitis related to NS. Within the complex diagnostic work-up that is required in cerebral vasculitis related to NS sufficient angiographic imaging as digital subtraction angiography or MRI vessel wall imaging and tissue biopsy are of particular significance as they can detect vascular changes caused by inflammatory processes.

Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.

Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium. Haplotypes were studied to confirm a common ancestry for the two most common recurrent variants identified in this study. A trained machine learning model was used to compare muscle MRI scans in ACTN2 myopathy with other neuromuscular diseases to identify a specific pattern of muscle involvement.

Results: The clinical phenotype ranged from asymptomatic to limb-girdle weakness and facial involvement and was depending on genotype. Cardiac and respiratory involvement were not common. Belgian families carrying the p.Ile134Asn variant and Basque-Spanish families carrying the p.Cys487Arg variant each showed unique haplotypes supporting respective common ancestry. Available muscle biopsies showed non-specific changes. In muscle imaging, the most affected muscles were the glutei minor, glutei medius, hamstrings, tibialis anterior, and soleus. A machine learning model showed that the most differentiating features in dominant ACTN2 myopathy were the involvement of the tibialis anterior and gluteus medius muscles and preservation of the quadratus femoris, gastrocnemius lateralis, and tensor fasciae latae muscles.

Conclusion: We provide new insights into genetic, clinical, and muscle imaging characteristics of non-congenital dominant ACTN2 myopathy, broadening the phenotypic spectrum of muscle disorders caused by ACTN2 variants.

Background: Tourette syndrome (TS) is a prevalent neurodevelopmental disorder with an uncertain etiology. Numerous neuroimaging studies have investigated patients with TS, but their conclusions remain inconsistent. The current study attempted to provide an unbiased statistical meta-analysis of published neuroimaging studies of TS.

Methods: A comprehensive literature search was conducted to identify voxel-based whole-brain morphology (VBM) and functional magnetic resonance imaging (fMRI) studies related to TS. Two separate meta-analyses of neurofunctional activation and gray matter volume (GMV) were performed using a seed-point-based d-mapping software package, followed by joint and subgroup analyses.

Results: 11 VBM studies and 18 fMRI studies were included in this study. We found that grey matter volumes were significantly decreased in the right anterior cingulate/paracingulate gyri and the left postcentral gyrus; while the cerebellum, bilateral cortico-spinal projections, and striatum showed increased GMV in patients with TS. In fMRI studies, patients with TS showed overactivation in the right superior frontal gyrus and right superior temporal gyrus, and significant hypoactivation in left SMA. In the multimodal studies, TS patients showed that there was an overlap between decreased GMV and hypoactivation in the right median cingulate/paracingulate gyri.

Conclusion: Abnormal alterations in the structure and function of the brain regions may play a role in the pathogenesis of TS in patients, and may be used as an imaging indicator for patients with TS to be diagnosed.

Objectives: The ability to differentiate epileptic- and non-epileptic events is challenging due to a lack of reliable molecular seizure biomarker that provide a retrospective diagnosis. Here, we use next generation sequencing methods on whole blood samples to identify changes in RNA expression following seizures.

Methods: Blood samples were obtained from 32 patients undergoing video electroencephalogram (vEEG) monitoring. Blood samples were collected in PaxGene tubes at baseline (admission) and following a seizure event (4-6 h and 24 h later or discharge). EEG and video of clinical events were reviewed by the clinical team and study epileptologist and were classified as epileptic seizure, psychogenic nonepileptic spell (PNES), or other. RNA was extracted from blood and RNA expression was determined using RNA-sequencing.

Results: We show significant differences in RNA profiles between patients that did or did not experience an epileptic seizure. Compared to baseline patients with PNES show large increases in RNA expression 4-6 h and 24 h post seizure. Conversely, genes that changed following epileptic seizure showed more modest changes associated with a decrease in immune system function. Transcript usage was changed between patients with PNES and epileptic seizure at all three time points examined. Lists of genes differentially expressed following PNES or epileptic seizure vs. all baseline samples were used as classifiers for prediction. Models generated using random forest and radial support vector machine algorithms were 100% accurate at predicting both PNES and epileptic seizures.

Significance: These data suggest that blood gene expression changes may have utility to retrospectively identify patients who have suffered a seizure or seizure-like event as a cause of transient loss of consciousness.

Impulse Control Disorders (ICDs) are increasingly recognized as a significant non-motor complication in Parkinson's disease (PD), impacting patients and their caregivers. ICDs in PD are primarily associated with dopaminergic treatments, particularly dopamine agonists, though not all patients develop these disorders, indicating a role for genetic and other clinical factors. Studies over the past few years suggest that the mesocorticolimbic reward system, a core neural substrate for impulsivity, is a key contributor to ICDs in PD. Recent advances in neuroimaging have begun to unravel the neurobiological diversity of ICD subtypes. Moreover, recent studies provide valuable insights into the clinical and biologic risk factors for ICDs that could be used as indicators for the development of future preventive strategies or targeted interventions. Indeed, current treatment strategies, which often involve reducing or discontinuing dopamine agonists, are limited in efficacy. Emerging therapies, including behavioral interventions and continuous drug delivery methods, show promise, though further research is needed. This paper provides an updated review of ICD prevalence, mechanisms, assessment, and novel management approaches.

Background: BDNF has increasingly gained attention as a key molecule controlling remyelination with a prominent role in neuroplasticity and neuroprotection. Still, it remains unclear how BDNF relates to clinicoradiological characteristics particularly at the early stage of the disease where precise prognosis for the further MS course is crucial.

Methods: BDNF, NfL and GFAP concentrations in serum and CSF were assessed in 106 treatment naïve patients with MS (pwMS) as well as 73 patients with other inflammatory/non-inflammatory neurological or somatoform disorders using a single molecule array HD-1 analyser. PwMS were evaluated for highly active profiles by applying the aggressive disease course criteria proposed by ECTRIMS. Serum/CSF values were logarithmically transformed and compared across groups using one-way ANOVA, while correlations were calculated using Pearson's correlations. ROC analysis and AUC comparisons for diagnostic performance of the three biomarkers were computed in an explorative analysis.

Results: Serum BDNF (sBDNF) concentrations were higher in treatment naïve pwMS with disease onset after the age of 40 years (p = 0.029), in pwMS with ≥2 gadolinium-enhancing lesions (p = 0.009) and with motor, cerebellar, cognitive or sphincter symptoms at onset (p = 0.036). BDNF correlated positively with NfL (r = 0.198, p = 0.014) and GFAP (r = 0.253, p = 0.002) in serum, but not in CSF. Neurological patients with an acute inflammatory relapse showed significantly higher sBDNF levels (p = 0.03) compared to somatoform controls, while patients without acute relapse did not differ from somatoform controls (p = 0.4). Better diagnostic performance was found for sBDNF than sNfL and sGFAP in differentiating between patients with vs. without 2 or more gadolinium-enhancing lesions (p < 0.05) and for sBDNF as compared to sNfL for separating patients with disease onset after vs. before age of 40 years.

Conclusion: In pwMS, BDNF serum levels differ depending on disease-related characteristics, suggesting that not only inflammatory activity but also remyelination capacities may vary with disease severity. BDNF is increased when other biomarkers of neuroaxonal damage and neurodegeneration, such as NfL and GFAP, are elevated, possibly as a compensatory mechanism, and reflect possibly further pathophysiological aspects in MS beyond NfL and GFAP, probably including an apoptotic role for BDNF in neuroinflammation.

Background: Drooling, defined as the unintentional loss of saliva from the anterior oral cavity, remains poorly understood in terms of the underlying clinical factors in people with Parkinson's disease (PwP). This study aims to clarify these factors by analyzing predictors and secondarily the correlates with the severity of drooling in PwP.

Methods: We conducted a cross-sectional study involving 42 PwP with drooling and 59 without drooling. Clinical assessments were performed, and the primary outcome was the item 2.2 Saliva and drooling of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. The Mann-Whitney test was used to compare the distribution differences in clinical variables between PwP with and without drooling. The Spearman test was used to examine correlations with drooling, and ordinal logistic regression was used to examine predictors of drooling.

Results: PwP with drooling showed significantly greater impairments in axial signs, posture, facial expression, speech, swallowing, oromotor, motor and non-motor domains than PwP without drooling. Longer disease duration, higher disease severity, levodopa equivalent daily dose, axial signs, unstimulated salivary flow rate, and impairments in speech, posture, facial expression, swallowing, oromotor, motor and non-motor domains were significantly correlated with a higher score on the item 2.2. Male sex, poorer swallowing, oromotor and speech functions were strong predictors of higher scores on the item 2.2 Saliva and drooling.

Conclusions: Male PwP with swallowing disorders, oromotor and speech impairments are significantly more likely to have severe drooling. Targeted interventions aimed at these swallowing, oromotor, and speech impairments may offer promising approaches to reducing drooling severity in PwP.

Background: Patients with Parkinson's disease (PD) and atypical parkinsonian syndromes are at increased risk of falls and should be actively screened and treated for osteoporosis. In 2024, the Royal Australian College of General Practitioners (RACGP) revised their practice guidelines for diagnosing and managing osteoporosis in postmenopausal women and men aged over 50 years.

Objective: We conducted the first Australian study to audit these guidelines in patients with PD and atypical parkinsonian syndromes.

Method: We audited all PD, Dementia with Lewy Bodies, Progressive Supranuclear Palsy and Multiple System Atrophy cases attending our neurology service between January and March 2024 against the RACGP osteoporosis guidelines. We identified patients at risk of osteoporosis or minimal trauma fractures and assessed if they had been referred to their general practitioner (GP) for appropriate management or were already receiving appropriate osteoporosis treatment.

Results: This audit evaluated 230 patients, 199 of which had PD. We identified 78 patients over the age of 50 years with risk factors that should trigger a GP bone health assessment as per the guidelines. Twenty-six of these patients were already being managed appropriately. However, only 12 of the remaining 52 'at risk' patients (23%) were directed to seek screening for osteoporosis by their GP, leaving 77% (40/52) without appropriate guidance.

Conclusion: Our major recommendations include following the guidelines and referring patients for a bone health screen with their GP if they have risk factors for osteoporosis. This audit highlighted that assessment of osteoporosis and fracture risk by Specialists needs to be improved.