Journal of Clinical Neurology最新文献

Background and purpose: CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature.

Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeat-primed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats.

Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients.

Conclusions: Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background and purpose: Episodic ataxia type 2 (EA2) is characterized by recurrent vertigo and ataxia due to mutations in CACNA1A that encodes the α_1A-subunit of the P/Q-type voltage-gated calcium channel. This study aimed to determine intellectual function in EA2.

Methods: During 2019-2023, 13 patients (6 males, age range=10-52 years, median age=29 years) with a genetically confirmed diagnosis of EA2 had their intellectual function evaluated using the Korean versions of the Wechsler Intelligence Scales (version IV) for adults or children in 3 referral-based university hospitals in South Korea.

Results: The full-scale intelligence quotients (FSIQs) among the 13 patients were below the average (90-109) in 11, low average (80-89) in 5 (38.5%), borderline (70-79) in 1 (7.7%), and indicated intellectual disability (≤69) in 5 (38.5%). These patterns of cognitive impairments were observed in all four of the following subtests: verbal comprehension, perceptual reasoning, working memory, and processing speed. The FSIQ was not correlated with the ages at onset for vertigo and ataxia (Pearson correlation: p=0.40).

Conclusions: Patients with EA2 may have hidden intellectual disabilities even without a history of epilepsy or administration of antiepileptic drugs, and should be considered for genetic counseling and therapeutic interventions. Given the availability of medication to control episodic vertigo and ataxia, early diagnosis and management are important in preventing irreversible brain dysfunction in EA2.

Background and purpose: The Karolinska Sleepiness Scale (KSS) is widely used for assessing current level of sleepiness, but it has not been validated in South Korea. This study aimed to validate the KSS using the Stanford Sleepiness Scale (SSS), polysomnography (PSG), and electroencephalography (EEG).

Methods: The sample consisted of 27 adult participants in this study aged 40.5±7.7 years (mean±standard deviation) and included 22 males. They completed questionnaires and underwent EEG recording and overnight PSG. The KSS was completed from 18:00 to 24:00 every 2 hours and following PSG (at 07:00). KSS scores changed over time and in particular increased with the time since waking, with the score peaking at 24:00.

Results: Convergent validity of the KSS was verified by performing a Spearman correlation analysis between the KSS and SSS (r=0.742, p<0.01). Concurrent validity of the KSS was verified by performing a Spearman correlation analysis between the KSS administered before sleep and the sleep onset latency measured using PSG (r=-0.456, p<0.05). Alpha waves were measured 5 minutes before administering the KSS, and the KSS scores were compared with these alpha waves. There were no significant correlations observed between the KSS scores and alpha waves measured in the left occipital area (O1), left frontal area (F3), or left central area (C3). In addition, Spearman correlation analyses of the difference between KSS scores and alpha waves measured at O1, F3, and C3 produced no significant results.

Conclusions: This study verified the convergent validity and concurrent validity of the KSS, and confirmed the capabilities of this scale in assessing sleepiness changes over time.

Background and purpose: The wearing-off (WO) phenomenon is the most common motor complication in advanced Parkinson's disease (PD), but its identification remains challenging. The 9- and 19-item Wearing-off Questionnaires (WOQ-9 and WOQ-19) are self-assessment tools for motor and nonmotor symptoms that are widely used for WO screening. We produced Korean versions of the WOQ-19 and WOQ-9 (K-WOQ-19 and K-WOQ-9) and investigated their validity and reliability.

Methods: We used the translation-back translation method to produce K-WOQ-19 and K-WOQ-9, which were self-administered by 124 patients with PD. We conducted in-depth 10-minute interviews for confirming the presence of the WO phenomenon, and then stratified the participants into groups with and without WO. Diagnostic accuracy was assessed byanalyzing receiver operating characteristic curves. Concurrent validity was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) andthe Hoehn and Yahr stage with Spearman's rank correlation analysis. Reliability was assessedbased on test-retest Cohen's kappa (κ) values and intraclass correlation coefficients (ICCs).

Results: The optimal cutoff scores on the K-WOQ-19 and K-WOQ-9 for WO screening were 4 and 2, respectively. The test-retest ICCs of K-WOQ-19 and K-WOQ-9 were 0.943 and 0.938, respectively. Nineteen of the combined 20 items in K-WOQ-19 and K-WOQ-9 showed moderate-to-substantial agreement (κ=0.412-0.771, p<0.001). The scores on the translated scales were significantly correlated with MDS-UPDRS IV scores.

Conclusions: K-WOQ-19 and K-WOQ-9 are reliable and valid tools for detecting WO, with optimal cutoff scores of 4 and 2, respectively.

Background and purpose: The prevalence of Alzheimer's dementia (AD) is increasing as populations age, causing immense suffering for patients, families, and communities. Unfortunately, no treatments for this neurodegenerative disease have been established. Predicting AD is therefore becoming more important, because early diagnosis is the best way to prevent its onset and delay its progression.

Methods: Mild cognitive impairment (MCI) is the stage between normal cognition and AD, with large variations in its progression. The disease can be effectively managed by accurately predicting the probability of MCI progressing to AD over several years. In this study we used the Alzheimer's Disease Neuroimaging Initiative dataset to predict the progression of MCI to AD over a 3-year period from baseline. We developed and compared various recurrent neural network (RNN) models to determine the predictive effectiveness of four neuropsychological (NP) tests and magnetic resonance imaging (MRI) data at baseline.

Results: The experimental results confirmed that the Preclinical Alzheimer's Cognitive Composite score was the most effective of the four NP tests, and that the prediction performance of the NP tests improved over time. Moreover, the gated recurrent unit model exhibited the best performance among the prediction models, with an average area under the receiver operating characteristic curve of 0.916.

Conclusions: Timely prediction of progression from MCI to AD can be achieved using a series of NP test results and an RNN, both with and without using the baseline MRI data.

Background and purpose: Visual perceptual learning (VPL) may improve visual field defects (VFDs) after chronic stroke, but the optimal training duration and location remain unknown. This prospective study aimed to determine the efficacy of 8 weeks of VFD-customized visual discrimination training in improving poststroke VFDs.

Methods: Prospectively enrolled patients with poststroke VFDs initially received no training for 8 weeks (no-training phase). They subsequently underwent our customized VPL program that included orientation-discrimination tasks in individualized blind fields and central letter-discrimination tasks three times per week for 8 weeks (training phase). We analyzed the luminance detection sensitivity and deviation as measured using Humphrey visual field tests before and after the no-training and training phases. The vision-related quality of life was assessed at baseline and at a 16-week follow-up using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25).

Results: Changes in mean total deviation (MTD) scores were greater during the training phase than during the no-training phase (defective hemifield, p=0.002; whole field, p=0.004). The MTD scores improved during the training phase (defective hemifield, p=0.004; whole field, p=0.016), but not during the no-training phase (defective hemifield, p=0.178; whole field, p=0.178). The difference between the improved and worsened areas (≥6 dB changes in luminance detection sensitivity) was greater during the training phase than during the no-training phase (p=0.009). The vision-specific social functioning subscore of the NEI-VFQ-25 improved after the 16-week study period (p=0.040).

Conclusions: Our 8-week VFD-customized visual discrimination training protocol may effectively improve VFDs and vision-specific social functioning in chronic stroke patients.

Background and purpose: Alzheimer's disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD.

Methods: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar.

Results: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers.

Conclusions: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele.