Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging.

Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML.

Association between motor symptoms of Parkinson's disease and swallowing disorders.

BACKGROUND: Parkinson's disease (PD) presents with motor symptoms that hinder physical activity. This study aimed to thoroughly investigate swallowing dysfunction in patients with PD using videofluoroscopy (VF) and the Movement Disorder Society (MDS)-Unified PD Rating Scale (UPDRS) sub-scores. METHODS: This study was part of an intervention project to evaluate the effectiveness of cervical percutaneous interferential current stimulation in patients with Hoehn and Yahr stages 2-4 PD. Baseline data, including swallowing-related indicators such as VF, were obtained and compared to the MDS-UPDRS sub-scores including rigidity, tremor, postural instability/gait difficulty, and limb scores. RESULTS: Twenty-seven patients were included in this study. In the VF analysis, laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecular residue, and pharyngeal residue were observed with remarkable frequency. The multivariate analysis revealed that the mean rigidity score of UPDRS was an independent and significantly correlated factor with laryngeal penetration/aspiration during the ingestion of 10 mL of water (odds ratio 1.294, 95% confidence interval 1.035-1.617; p = 0.024). CONCLUSION: This study revealed a correlation between muscle rigidity and laryngeal penetration or aspiration risk. The detailed comparative analysis of various individual PD symptoms and swallowing disorders was substantial, which enabled early detection of the risk of swallowing disorder and the implementation of appropriate measures. TRIAL REGISTRATION NUMBER: jRCTs062220013.

Detailed findings of videofluoroscopic examination among patients with Parkinson's disease on the effect of cervical percutaneous interferential current stimulation.

Introduction: Parkinson's disease (PD) leads to various types of swallowing disorders. We investigated the effect of cervical percutaneous interferential current stimulation on dysphagia. By conducting detailed qualitative and quantitative analysis of videofluoroscopic examination, we aimed to understand dysphagia in patients with PD and investigate its effects on swallowing function. Methods: Patients received cervical percutaneous interferential current stimulation for 20 min twice a week for 8 weeks. In this exploratory study, we evaluated aspiration/laryngeal penetration, oral cavity residue, vallecular residue, and pharyngeal residue. In addition, we performed temporal analysis. Results: Twenty-five patients were completely evaluated. At baseline, the proportions of laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecula residue, and pharyngeal residue were 40.0, 88.0, 72.0, 60.0, and 16.0%, respectively. Conversely, pharyngeal transit time, laryngeal elevation delay time, pharyngeal delay time, and swallowing reflex delay were nearly within the normal ranges. Cervical percutaneous interferential current sensory stimulation improved only oral cavity residue at the end of the intervention, from 88.0 to 56.0%. Discussion: Patients with PD demonstrated remarkably high frequencies of residues in the oral and pharyngeal regions. The usefulness of cervical interferential current stimulation was partially demonstrated for oral cavity residue. Considering that PD exhibits diverse symptoms, further accumulation of cases and knowledge is warranted. Trial registration: jRCTs062220013.

Swallowing sound index analysis using electronic stethoscope and artificial intelligence for patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Several noninvasive tools assess swallowing disorders, including electronic stethoscope artificial intelligence (AI) analysis for remote diagnosis, with the potential for telemedicine. This study investigated the swallowing sound index in patients with Parkinson's disease (PD). METHODS: This single-arm, open-label trial assessed the impact of cervical percutaneous interferential current stimulation on swallowing in patients with PD classified as Hoehn-Yahr stages 2-4. Stimulation was conducted for 8 weeks. Baseline data were used to examine the link between the swallowing sound index and indicators such as videofluoroscopy (VF). Furthermore, we examined changes in the swallowing sound index after the intervention. RESULTS: Twenty-five patients were included. The swallowing sound index in patients with PD was higher than that in those with amyotrophic lateral sclerosis but considerably lower than that in healthy controls. The number of patients with normal EAT-10 scores positively correlated with the swallowing sound index, whereas elevated C-reactive protein levels were negatively correlated with the swallowing sound index. However, the index displayed no correlation with other indicators, including the VF results. Despite the intervention, the index remained unchanged throughout the study. CONCLUSION: In patients with PD, a decrease in the swallowing sound index suggests a potential association between swallowing disorders and the risk of aspiration pneumonia. TRIAL REGISTRATION NUMBER: jRCTs062220013.

Swallowing sound evaluation using an electronic stethoscope and artificial intelligence analysis for patients with amyotrophic lateral sclerosis.

Background and purpose: Non-invasive, simple, and repetitive swallowing evaluation is required to prevent aspiration pneumonia in neurological care. We investigated the usefulness of swallowing sound evaluation in patients with amyotrophic lateral sclerosis (ALS) using our new electronic stethoscope artificial intelligence (AI) analysis tool. Methods: We studied patients with ALS who provided written informed consent. We used an electronic stethoscope, placed a Bluetooth-enabled electronic stethoscope on the upper end of the sternum, performed a 3-mL water swallow three times, and remotely identified the intermittent sound components of the water flow caused at that time by AI, with the maximum value as the swallowing sound index. We examined the correlation between the swallowing sound index and patient background, including swallowing-related parameters. Results: We evaluated 24 patients with ALS (age 64.0 ± 11.8 years, 13 women, median duration of illness 17.5 months). The median ALS Functional Rating Scale-Revised (ALSFRS-R) score was 41 (minimum 18, maximum 47). In all cases, the mean swallowing sound index was 0.209 ± 0.088. A multivariate analysis showed that a decrease in the swallowing sound index was significantly associated with a low ALSFRS-R score, an ALSFRS-R bulbar symptom score, % vital capacity, tongue pressure, a Mann Assessment of Swallowing Ability (MASA) score, and a MASA pharyngeal phase-related score. Conclusion: Swallowing sound evaluation using an electronic stethoscope AI analysis showed a correlation with existing indicators in swallowing evaluation in ALS and suggested its usefulness as a new method. This is expected to be a useful examination method in home and remote medical care.

Impact of neck percutaneous interferential current sensory stimulation on swallowing function in patients with Parkinson's disease: A single-arm, open-label study protocol.

Background: Parkinson's disease (PD) can lead to swallowing dysfunction, resulting in aspiration pneumonia. Among the types of swallowing disorders, a characteristic and serious problem associated with PD is silent aspiration due to pharyngeal and laryngeal hypoesthesia. Methods: This single-arm, open-label study aims to evaluate the effectiveness of percutaneous neck interferential current sensory stimulation in enhancing swallowing function in patients with PD. The efficacy and safety of percutaneous neck interferential current sensory stimulation will be investigated for patients diagnosed with PD, based on the Movement Disorder Society criteria, of Hoehn-Yahr stages 2-4. The patients will receive neck percutaneous interferential current sensory stimulation for 20 min twice a week for 8 weeks using a Gentle Stim® (FoodCare Co., Ltd., Kanagawa, Japan) device. Once the intervention is initiated, evaluations will be performed every 4 weeks for a 16-week period. The primary endpoint to be assessed is the proportion of patients with normal cough with 1% citric acid at the end of the intervention (8 weeks after intervention initiation) compared with that at the beginning. This clinical trial will examine the usefulness of percutaneous neck interferential current sensory stimulation in patients with PD. In addition, this study will use novel instruments, such as multichannel surface electromyography and electronic stethoscope, to evaluate swallowing function. Discussion: This novel evaluation can provide insights into dysphagia in patients with PD and the usefulness of percutaneous neck interferential current stimulation. This exploratory study is limited by its single-arm, open-label design and small size. Trial registration number: jRCTs062220013; pre-results.

Novel partial deletions, frameshift and missense mutations of CSF1R in patents with CSF1R-related leukoencephalopathy.

BACKGROUND AND PURPOSE: Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features. METHODS: Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study. RESULTS: CSF1R mutations were identified in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C-terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features. CONCLUSIONS: Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.

FXTAS is difficult to differentiate from neuronal intranuclear inclusion disease through skin biopsy: a case report.

BACKGROUND: Both fragile X-associated tremor/ataxia syndrome (FXTAS) and late-onset neuronal intranuclear inclusion disease (NIID) show CGG/GGC trinucleotide repeat expansions. Differentiating these diseases are difficult because of the similarity in their clinical and radiological features. It is unclear that skin biopsy can distinguish NIID from FXTAS. We performed a skin biopsy in an FXTAS case with cognitive dysfunction and peripheral neuropathy without tremor, which was initially suspected to be NIID. CASE PRESENTATION: The patient underwent neurological assessment and examinations, including laboratory tests, electrophysiologic test, imaging, skin biopsy, and genetic test. A brain MRI showed hyperintensity lesions along the corticomedullary junction on diffusion-weighted imaging (DWI) in addition to middle cerebellar peduncle sign (MCP sign). We suspected NIID from the clinical picture and the radiological findings, and performed a skin biopsy. The skin biopsy specimen showed ubiquitin- and p62-positive intranuclear inclusions, suggesting NIID. However, a genetic analysis for NIID using repeat-primed polymerase chain reaction (RP-PCR) revealed no expansion detected in the Notch 2 N-terminal like C (NOTCH2NLC) gene. We then performed genetic analysis for FXTAS using RP-PCR, which revealed a repeat CGG/GGC expansion in the FMRP translational regulator 1 (FMR1) gene. The number of repeats was 83. We finally diagnosed the patient with FXTAS rather than NIID. CONCLUSIONS: For the differential diagnosis of FXTAS and NIID, a skin biopsy alone is insufficient; instead, genetic analysis, is essential. Further investigations in additional cases based on genetic analysis are needed to elucidate the clinical and pathological differences between FXTAS and NIID.

Prospective Memory Deficits in Multiple Sclerosis: Voxel-based Morphometry and Double Inversion Recovery Analysis.

Objective Prospective memory (PM) is an important social cognitive function in everyday life. PM is one of the most affected cognitive domains in multiple sclerosis (MS) patients. Gray matter (GM) atrophy and plaques have been attracting attention for various cognitive impairments in MS patients. This study aimed to clarify the atrophic GM regions associated with PM deficits and investigate the relationship between the atrophic GM regions and GM plaques. Methods Twenty-one MS patients and 10 healthy controls (HCs) underwent neuropsychological tests and MRI. PM was assessed using subtests of the Rivermead Behavioural Memory Test. A lesion symptom analysis was performed using voxel-based morphometry (VBM). We then evaluated GM plaques in the corresponding areas using double inversion recovery (DIR). Results MS patients showed lower PM scores than HCs (p=0.0064). The GM volume of MS patients tended to be lower than those of HCs. VBM analyses revealed correlations of the PM score with the orbital part of the left inferior frontal gyrus, the left hippocampus, and the right parahippocampus. There was no GM plaque in the orbital part of the left inferior frontal gyrus and the right parahippocampus. Only one patient (4.8%) had GM plaque in the left hippocampus. Conclusion The left inferior frontal gyrus, the left hippocampus, and the right parahippocampus were associated with PM in MS, whereas these atrophic GM regions were not associated with GM plaque. Regardless of the location of plaques on DIR, both PM deficit and GM atrophy should be detected using neuropsychological tests and VBM in MS patients.

The Insular Cortex, Alzheimer Disease Pathology, and Their Effects on Blood Pressure Variability.

Recent findings indicate that the human cardiovascular system is regulated by a cortical network comprised of the insular cortex (Ic), anterior cingulate gyrus, and amygdala which is necessary for the regulation of the central autonomic network system. Alzheimer disease (AD) affects the Ic at a preclinical stage. The pathology of AD at the Ic is suggested to predispose the cardiovascular system to detrimental changes such as increased blood pressure variability (BPV). In this review article, we focus on the physiology of the Ic in the relationship between the central autonomic network and BPV. We provide a summary of the published evidence regarding the relationship between Ic damage and exaggerated BPV in the context of AD pathology.

A case of seronegative longitudinally extensive transverse myelitis with possible neuro sweet disease.

•Neuro sweet disease (NSD) rarely exhibits spinal cord involvement.•We experienced a case of NSD with longitudinally extensive transverse myelitis.•The shape of gadolinium enhanced lesion of spinal MRI was characteristic.•Above mentioned finding might be useful for diagnosis of neuro sweet disease.

Insular cortex lesion and autonomic instability in a herpes simplex virus encephalitis patient.

The cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex, anterior cingulate gyrus, and amygdala. Because the insular cortex often tends to be damaged in patients with herpes simplex virus (HSV) encephalitis, the autonomic instability observed in these patients was suggested to be moderated by an insular cortex lesion. Here, we report the case of a 51-year-old Japanese male who was hospitalized following a collapse 5 days earlier; he was diagnosed as herpes encephalitis. Diffusion-weighted MRI revealed asymmetric right greater hyperintensity throughout his insular cortex and anterior cingulate gyrus. At 1 week after admission, transthoracic echo showed diffuse hypokinesis in the left ventricle (LV). Cardiac 123I-meta-iodobenzylguanidine uptake (123I-MIBG) scintigraphy revealed reduced uptake in the inferior and posterior wall. Electrocardiograhy at rest showed that the coefficient variation of RR intervals (CVR-R) was reduced, and the corrected QT (QTc) interval length was prolonged. In this HSV encephalitis patient, signs of a right insular cortex lesion and autonomic instability were observed: LV hypokinesis, regional reduced 123I-MIBG uptake, decreased CVR-R, and QTc interval prolongation. Our patient's autonomic instability may thus be derived from disrupted autonomic balance due to the right insular cortex lesion.