Intermediate phenotype between CMT2Z and DIGFAN associated with a novel MORC2 variant: a case report.

Charcot-Marie-Tooth disease type 2Z is caused by MORC2 mutations and presents with axonal neuropathy. MORC2 mutations can also manifest as developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN). We report a patient exhibiting an intermediate phenotype between these diseases associated with a novel MORC2 variant. A literature review revealed that the genotype‒phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes.


Complete nanopore repeat sequencing of SCA27B (GAA-FGF14 ataxia) in Japanese.

Journal of Neurology, Neurosurgery, and Psychiatry


A Case of Anti-NXP2 Antibody-positive Juvenile Dermatomyositis with Characteristic Fascial Thickening on Muscle Ultrasound and Improvement with Immunotherapy

We herein report a 12-year-old boy who presented with a fever, erythematous rash on the cheeks, back pain, and dysphagia. Blood tests revealed increased creatine kinase levels, and muscle ultrasonography (MUS) revealed characteristic fascial thickening in the lumbar paraspinal muscles, where myalgia was prominent. Sarcoplasmic expression of myxovirus-resistant protein A on a muscle biopsy and the presence of anti-nuclear matrix protein 2 (NXP2) antibodies confirmed the diagnosis of dermatomyositis. Prednisolone and intravenous immunoglobulin therapy improved the clinical and laboratory parameters as well as fascial thickening. MUS is useful for evaluating fasciitis associated with anti-NXP2 autoantibodies and monitoring therapeutic efficacy.


Segmental Zoster Paresis Accompanied by Horner's Syndrome.

We herein report a 90-year-old immunocompromised woman who developed right upper limb weakness and right ptosis with a miotic pupil 1 week after oral therapy for zoster on the right T2 dermatome. The right pupil was dilated with instillation of 1% apraclonidine, indicating Horner's syndrome. The patient was treated with intravenous acyclovir and methylprednisolone. Focal weakness related to zoster, generally known as segmental zoster paresis, improved over five months, but Horner's syndrome remained. We suggest that aggressive intravenous treatment should be considered for rare cases of zoster that occur with a combination of these two neurological conditions.


Autosomal Recessive Spinocerebellar Ataxia Type 9 With a Response to Phosphate Repletion: A Case Report.

This provides Class IV evidence. This is a single observational study without controls.


Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies

In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.


M1/precuneus ratio as a surrogate marker of upper motor neuron sign in ALS

To investigate whether primary motor cortex (M1) volume measured with an automated approach in MRI reflects upper motor neuron dysfunction and whether it can serve as a potential diagnostic and/or disease-tracking biomarker for amyotrophic lateral sclerosis (ALS). In this retrospective study, we enrolled 95 subjects, including 33 possible or laboratory supported probable ALS, 26 probable or definite ALS (Prob/Def), 2 primary lateral sclerosis patients, 8 progressive muscular atrophy patients, 19 normal controls (NC) and 7 ALS patients having a second structural MRI scan. Some subjects also underwent functional MRI. We calculated M1, primary sensory cortex, precuneus volumes, and total gray matter volume (TGMV) with FreeSurfer. The sensorimotor network (SMN) was identified using independent component analysis. The M1/precuneus ratio showed a significant difference between the NC and Prob/Def groups (p < 0.05). The diagnostic accuracy of the M1/precuneus ratio was moderate for distinguishing Prob/Def from NC (cutoff = 1.00, sensitivity = 0.42, specificity = 0.90). Two of eight cases without upper motor neuron dysfunction could be diagnosed with ALS using M1/precuneus ratio as a surrogate marker. A negative correlation between M1/precuneus ratio and functional activity was found in Brodmann area 6 in the SMN in all subjects. TGMV tended to decrease with disease progression (p = 0.04). The M1/precuneus volume ratio, associated with the SMN, may have potential as a surrogate biomarker of upper motor neuron dysfunction in ALS. Furthermore, TGMV may serve as an ALS disease-tracking biomarker.


An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. This trial began data collection in September 2021 and is expected to be completed in October 2023. This study can provide useful data to understand the characteristics of EPI-589. Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6. DERR1-10.2196/42032.


A case of anti-NT5c1A antibody-seropositive inclusion body myositis associated with severe dysphagia and prominent forearm weakness


Application of ultrasound in a case of eosinophilic fasciitis mimicking stiff-person syndrome

Eosinophilic fasciitis (EF) is a rare disorder characterized by muscle stiffness mimicking other neuromuscular diseases. The diagnosis of EF is made on the basis of typical skin lesions. We report a case of a 36-year-old male patient with suspected stiff-person syndrome (SPS), who presented with progressive limb muscle stiffness and limited mobility of both wrists without obvious skin changes. Ultrasound revealed fascial thickening of bilateral upper and lower limb muscles and enlargement of hypoechoic tissues around the flexor digitorum tendons of the wrist. Skin and fascia biopsy confirmed the diagnosis of EF. Prednisolone therapy resulted in the improvement of muscle stiffness and tightness. Our findings suggest the need to consider connective tissue diseases such as EF in a patient with atypical features of SPS. Ultrasound is helpful for visualizing the causes of muscle stiffness and joint contractures in EF patients.


Early diagnosis of amyotrophic lateral sclerosis based on fasciculations in muscle ultrasonography: A machine learning approach.

Fasciculation detected in relevant muscles on MUS can contribute to the diagnosis of ALS from the early stage.

We investigated 100 patients with ALS, including 50 with early-stage ALS within 9 months from onset, and 100 without ALS. Fifteen muscles were bilaterally observed for 10 s each and the presence of fasciculations was recorded. Hierarchical clustering and nominal logistic regression, neural network, or ensemble learning were applied to the training cohort comprising the early-stage ALS to develop MUS-based diagnostic models, and they were tested in the validation cohort comprising the later-stage ALS.


Serum NfL and CHI3L1 for ALS and parkinsonian disorders in the process of diagnosis

Serum neurofilament light chain (NfL) and chitinase 3-like 1 (CHI3L1, also called YKL-40) concentrations are attractive candidate biomarkers for neurodegenerative disorders, which include amyotrophic lateral sclerosis (ALS) and parkinsonian disorders. We aimed to assess the diagnostic power of serum NfL and CHI3L1 concentrations with regard to the early diagnosis of ALS and Parkinson's disease (PD). We studied 157 individuals, which included 41 healthy controls, 8 patients with ALS mimics, 18 patients initially diagnosed with ALS (ID-ALS), 32 patients late-diagnosed with ALS (LD-ALS), 29 patients with PD, 12 patients with PD mimics, and 17 patients initially diagnosed with atypical parkinsonian disorders (ID-APDs) at the initial stage of diagnosis. Electrochemiluminescence was used to measure the concentrations of serum NfL and CHI3L1, the diagnostic performance of which was assessed using the area under the receiver operating curves (AUCs). The AUCs of serum NfL were 0.90 for discriminating ALS mimics from LD-ALS at the initial stage of diagnosis and 0.89 for discriminating ALS mimics from ALS (LD/ID-ALS). The AUCs of serum NfL were 0.76 for discriminating PD from PD mimics at the initial stage of diagnosis, and 0.80 for discriminating PD from APD. No significant difference existed in serum CHI3L1 concentrations between individuals with suspected ALS or parkinsonism (p = 0.14, and p = 0.44, respectively). Serum NfL had excellent and almost good diagnostic performances for patients with ALS and PD, respectively, at the initial stage of diagnosis, whereas no significant difference existed in serum CHI3L1 between any groups.


血管炎性ニューロパチー様の臨床像で発症した抗Hu抗体陽性脳脊髄炎の1例

血管炎性ニューロパチー様の臨床像で発症した抗Hu抗体陽性脳脊髄炎の1例


MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis


Peripheral nerve dysfunction in a patient with thyrotoxic periodic paralysis: Evidence from an axonal prolonged exercise test


The cerebellum is a common key for visuospatial execution and attention in Parkinson's disease

Cognitive decline affects the clinical course in patients with Parkinson's disease (PD) and contributes to a poor prognosis. However, little is known about the underlying network-level abnormalities associated with each cognitive domain. We aimed to identify the networks related to each cognitive domain in PD using resting-state functional magnetic resonance imaging (MRI). Forty patients with PD and 15 normal controls were enrolled. All subjects underwent MRI and the Mini-Mental State Examination. Furthermore, the cognitive function of patients with PD was assessed using the Montreal Cognitive Assessment (MoCA). We used independent component analysis of the resting-state functional MRI for functional segmentation, followed by reconstruction to identify each domain-related network, to predict scores in PD using multiple regression models. Six networks were identified, as follows: the visuospatial-executive-domain-related network ( = 0.54, < 0.001), naming-domain-related network ( = 0.39, < 0.001), attention-domain-related network ( = 0.86, < 0.001), language-domain-related network ( = 0.64, < 0.001), abstraction-related network ( = 0.10, < 0.05), and orientation-domain-related network ( = 0.64, < 0.001). Cerebellar lobule VII was involved in the visuospatial-executive-domain-related and attention-domain-related networks. These two domains are involved in the first three listed nonamnestic cognitive impairment in the diagnostic criteria for PD with dementia (PDD). Furthermore, Brodmann area 10 contributed most frequently to each domain-related network. Collectively, these findings suggest that cerebellar lobule VII may play a key role in cognitive impairment in nonamnestic types of PDD.


A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma


The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis


Magnetic resonance tractography exhibiting retrograde degeneration of the corticospinal tract in a patient with a unilateral spinal cord tumor


Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis


A case of led to diagnosis of malignancy by brachial plexus ultrasonography

腕神経叢エコー検査が契機となって悪性腫瘍が診断できた1例

A 72-year-old man admitted to our hospital due to severe pain and drop hand in the left arm. MRI and CT of the head and neck at an outside hospital showed no abnormality. Neurological findings revealed distal weakness in the left upper extremity, vague pain between the radial aspect of the left hand and the middle of the digits 1-3, as well as brisk reflexes in the left extremities. Small masses were palpable in the posterior neck, the lower jaw, and the left neck. Clinically, left radial neuropathy and cervical radiculopathy were suspected. We performed ultrasound of the nerve roots, brachial plexus, and the radial nerve. There was a mass compressing the left brachial plexus from the caudolateral direction. Additionally, nerve swelling in the left arm was identified. Skin biopsy over the mass suggested metastatic adenocarcinoma. Chest CT scan showed a mass in the upper right lobe suggestive of a lung cancer. We concluded that the pain was due to radial neuropathy and upper and middle trunk disturbance of the left brachial plexopathy, of which neuromuscular ultrasound was useful in diagnosis.


A method for differential diagnosis of parkinsonian syndromes

Neurological findings are important for the differential diagnosis of Parkinson's disease (PD), multiple system atrophy with predominant parkinsonian features (MSA-P), and progressive supranuclear palsy (PSP). There is currently no fast and reliable method to distinguish these patients. To address this, we propose a novel approach to measure midbrain and pons size using a longitudinal "one line" method from the mid-sagittal view. Structural images were acquired from 101 subjects who underwent 3.0 T MRI (20 controls, 44 PD, 20 MSA, 12 PSP, and 5 corticobasal syndrome). We measured the middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), midbrain, and pons. Brainstem size was measured by area or length of the longitudinal axis, which we named the "one line" method. We conducted intraclass correlation coefficients to assess the extent of agreement and consistency among raters, and receiver operating characteristic curves were used to determine diagnostic accuracy. Intraclass correlation coefficients (ICC) of MCP width were excellent in sagittal and axial sections while those of SCP width were moderate. There were also excellent ICCs between raters for "one line" method of the midbrain and pons, while areas showed good ICCs. "One line" method and area of the midbrain were better than SCP width for the differential diagnosis of PSP from MSA-P and PD. In contrast, there was no clearly superior measurement for differentially diagnosing MSA-P. The "one line" method was comparable with area for inter-rater agreement and diagnostic accuracy even though this was a simple and fast way.


PMP22-related disease: A novel splice site acceptor variant and intrafamilial phenotype variability.

PMP22 is the most frequent mutated gene in Charcot-Marie-Tooth disease (CMT) type 1A. Another phenotype, hereditary neuropathy with pressure palsies (HNPP), could be caused by PMP22 mutations. PMP22 encodes a peripheral myelin protein with molecular weight 22-kDa. Various pathomechanisms have been postulated in PMP22-related disease, including dysfunction due to missense mutations, and alteration of a gene dose due to duplication/deletion mutations. We identified a novel PMP22 splice site acceptor variant, c.179-1G>A, in a patient with adult-onset chronic generalized polyneuropathy and two asymptomatic family members. Pathophysiological features of the members mainly overlapped with those reported in HNPP, but broad intrafamilial clinical variations were observed. PMP22 transcripts lacking of exon 4 were produced by the variant, presumably leading to in-frame deletion of 47 amino acids. The variant was also shown to exert effect on dosage of PMP22 mRNA. The complex molecular pathology would lead to the unique clinical and pathophysiological conditions.


Guillan-Barre syndrome in local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients

Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.


未治療のサルコイドーシスに合併した進行性多巣性白質脳症

未治療のサルコイドーシスに合併した進行性多巣性白質脳症


Neurologic attack and dynamic perfusion abnormality in neuronal intranuclear inclusion disease