Altered cortical functional networks in Wilson's disease: A resting-state electroencephalogram study.

The neuropsychiatric symptoms are common in Wilson's disease (WD) patients. However, it remains unclear about the associated functional brain networks. In this study, source localization-based functional connectivity analysis of close-eye resting-state electroencephalography (EEG) were implemented to assess the characteristics of functional networks in 17 WD patients with neurological involvements and 17 healthy controls (HCs). The weighted phase-lag index (wPLI) was subsequently calculated in source space across five different frequency bands and the resulting connectivity matrix was transformed into a weighted graph whose structure was measured by five graphical analysis indicators, which were finally correlated with clinical scores. Compared to HCs, WD patients revealed disconnected sub-networks in delta, theta and alpha bands. Moreover, WD patients exhibited significantly reduced global clustering coefficients and small-worldness in all five frequency bands. In WD group, the severity of neurological symptoms and structural brain abnormalities were significantly correlated with disrupted functional networks. In conclusion, our study demonstrated that functional network deficits in WD can reflect the severity of their neurological symptoms and structural brain abnormalities. Resting-state EEG may be used as a marker of brain injury in WD.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Transcranial Alternating Current Stimulation in a Patient with Ataxia-Ocular Apraxia 2: a Case Report.

Ataxia-ocular apraxia 2 (AOA2) is a rare neurodegenerative autosomal recessive disorder with no effective treatment. In this study, we present the case of a patient diagnosed with AOA2, who experienced walking instability and uncoordinated movement. The patient underwent transcranial alternating current stimulation (tACS) treatment for 4 weeks with follow-up after 1 month. The effectiveness of the treatment was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), the Scale for the Assessment and Rating of Ataxia (SARA), the 9-Hole Peg Test (9HPT), and functional near-infrared spectroscopy (fNIRS). Following treatment, the patient's ataxia symptoms showed significant improvement and continued to be alleviated during the follow-up period, suggesting a lasting effect of tACS treatment. Our findings from this case study provide compelling evidence for the potential of tACS as a treatment option for AOA2.

Analysis of Exon Dosage Using Multiplex Ligation-Dependent Probe Amplification in Chinese Patients with Early-Onset Parkinson's Disease.

INTRODUCTION: Several studies have identified a number of genes associated with Parkinson's disease (PD). Genomic rearrangements (exon dosage variations) in these genes have emerged as significant, causing mutations. However, exon dosage variations in several PD genes were rarely investigated in Chinese patients. OBJECTIVE: This study was aimed at determining the prevalence of PD-causing genes' exon rearrangements in Chinese sporadic early-onset PD (EOPD) patients. METHODS: A total of 150 Chinese sporadic EOPD patients and 100 healthy controls were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was used to detect exon dosage in PD genes, including SNCA, PARKIN, UCHL1, PINK1, DJ1, LRRK2, and ATP13A2. Positive results were verified by real-time quantitative polymerase chain reaction. And exon sequencing was employed to screen for subtle mutations. Novel exon dosage variations were screened in families and controls. RESULTS: PARKIN exon rearrangements were detected in 10 (6.7%) patients, including a novel heterozygous duplication of PARKIN exons 1-4. Clinical investigation showed that the percentage of individuals with PARKIN exon rearrangements was higher in the younger patients. Notably, the MLPA screening detected a heterozygous deletion of UCHL1 exon 1 in a patient. MLPA analysis in the family detected the deletion in an asymptomatic sister, indicating incomplete penetrance. CONCLUSION: Exon copy number variations (CNVs) in the PARKIN gene are relatively common among Chinese sporadic EOPD patients, whereas exon CNVs in other known PD genes can also be detected. Our findings demonstrate that it is important to perform exon dosage analysis for several known PD genes to obtain a better mechanistic insight into PD pathogenesis.

Cerebral-Cerebellar Cortical Activity and Connectivity Underlying Sensory Trick in Cervical Dystonia.

OBJECTIVE: The objective of this study was to investigate the activity and connectivity of cerebral and cerebellar cortices underlying the sensory trick (ST) effects in patients with cervical dystonia (CD), using electroencephalography (EEG). METHODS: We recruited 15 CD patients who exhibited clinically effective ST and 15 healthy controls (HCs) who mimicked the ST maneuver. EEG signals and multiple-channel electromyography (EMG) were recorded simultaneously during resting and acting stages. EEG source analysis and functional connectivity were performed. To account for the effects of sensory processing, we calculated relative power changes as the difference in power spectral density between resting and the maneuver execution. RESULTS: ST induced a decrease in low gamma (30-50 Hz) spectral power in the primary sensory and cerebellar cortices, which remained lower than in HCs during the maintenance period. Compared with HCs, patients exhibited consistently strengthened connectivity within the sensorimotor network during the maintenance period, particularly in the primary sensory-sensorimotor cerebellum connection. INTERPRETATION: The application of ST resulted in altered cortical excitability and functional connectivity regulated by gamma oscillation in CD patients, suggesting that this effect cannot be solely attributed to motor components. The cerebellum may play important roles in mediating the ST effects.

Levodopa-Induced Ocular Dyskinesia in an Early-Onset Parkinson Disease Patient With GBA Mutation.

OBJECTIVES: The aim of this study was to report a case of levodopa-induced ocular dyskinesia in an early-onset Parkinson disease patient and to investigate the pathogenic gene. METHODS: We report the case of a 49-year-old male patient with a 13-year history of Parkinson disease. Involuntary eye movements were noticed after treatment with amantadine for limb dyskinesias. Levodopa-induced ocular dyskinesias involving repetitive, transient, and stereotyped rightward deviations of gaze appeared after intake of an antiparkinsonian drug. Limb dyskinesias also occurred simultaneously. We used a next-generation sequencing targeted gene panel and found a heterozygous missense mutation (p.R535H) in GBA. Direct Sanger sequencing verified the missense mutation. CONCLUSIONS: We report the case of an uncommon early-onset PD patient carrying a GBA mutation presenting ocular dyskinesia. Genetic screening may provide a better mechanistic insight into dyskinesias.

Six Visual Rating Scales as A Biomarker for Monitoring Atrophied Brain Volume in Parkinson's Disease.

The focus of our investigation was to determine the feasibility of using six visual rating scales as whole-brain imaging markers for monitoring atrophied brain volume in Parkinson's disease (PD). This was a prospective cross-sectional single-center observational study. A total of 98 PD patients were enrolled and underwent an MRI scan and a battery of neuropsychological evaluations. The brain volume was calculated using the online resource MRICloud. Brain atrophy was rated based on six visual rating scales. Correlation analysis was performed between visual rating scores and brain volume and clinical features. We found a significant negative correlation between the total scores of visual rating scores and quantitative brain volume, indicating that six visual rating scales reliably reflect whole brain atrophy in PD. Multiple linear regression-based analyses indicated severer non-motor symptoms were significantly associated with higher scores on the visual rating scales. Furthermore, we performed sample size calculations to evaluate the superiority of visual rating scales; the result show that using total scores of visual rating scales as an outcome measure, sample sizes for differentiating cognition injury require significantly fewer subjects (n = 177) compared with using total brain volume (n = 2524). Our data support the use of the total visual rating scores rather than quantitative brain volume as a biomarker for monitoring cerebral atrophy.

A "Triple Trouble" Case of Facioscapulohumeral Muscular Dystrophy Accompanied by Peripheral Neuropathy and Myoclonic Epilepsy.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. METHODS: Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing. RESULTS: The patient presented with mild facial weakness, humeral poly-hill sign, scapular winging, peroneal weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore, electrophysiology revealed severely demyelinated and axonal injury. The muscle and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated nerve fibers that significantly decreased with thin myelinated fibers and onion bulbs changes. Generalized sharp and sharp-slow wave complexes on electroencephalography support the diagnosis toward myoclonic epilepsy. In addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI fragment and permissive allele A, which corresponded with D4Z4 hypomethylation status in the family. Both the patient's mother and brother only presented the typical FSHD but lacked overlapping syndromes. However, no mutations for hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA and WES. CONCLUSIONS: The present study described a "tripe trouble" with FSHD, peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping syndromes and contributing to the credible diagnosis of atypical phenotype. It would provide a direct clue on medical care and genetic counseling.