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To investigate the possibility of local antigen presentation within the peripheral nerve in amyotrophic lateral sclerosis (ALS), cryostat sections of 83 peripheral nerve biopsies were stained for the demonstration of HLA-DR using a monoclonal antibody. Forty samples showed increased expression of HLA-DR in endoneurium. The phenotypic characteristics of the HLA-DR positive cells are chiefly Schwann cells, using S-100 protein as a marker. We did not detect any co-expression between HLA-DR and NF (axons) and HLA-DR and myelin marker. We also detected co-expression between HLA-DR and NGFr in a majority of HLA-DR positive cells. Inflammatory cells were infrequent, being detected only in 11 cases, predominantly around epineurial blood vessels. Motor and sensory nerve biopsies performed simultaneously showed higher expression of HLA-DR in motor nerves in 2 out of 4 patients. The significance of these findings is not clear. The presence of endoneurial cells expressing HLA-DR suggests that an autoimmune mechanism may be involved in ALS having Schwann as the main target.

Background: Impairment of visual fixation suppression (VS) in progressive supranuclear palsy (PSP) is not well documented., Objective: To evaluate the usefulness of impaired VS of caloric nystagmus as an index for differential diagnosis between PSP and Parkinson's disease (PD), which is often difficult, especially in the early stage., Methods: Subjects comprised 26 PSP patients and 26 PD patients clinically diagnosed at Tokyo Metropolitan Neurological Hospital. We retrospectively investigated VS of caloric nystagmus, horizontal pursuit, saccades, and horizontal optokinetic nystagmus recorded on direct-current-electronystagmography, and neuroradiological findings., Results: The median of the average VS% was 0% and 50.0% in PSP and PD patients, respectively. In PSP, VS was impaired even in the early stage of disease. We found a significant correlation between VS and velocity of saccades or maximum slow phase velocity of optokinetic nystagmus only in PSP patients. PSP patients with atrophy of the subthalamic nucleus or with decreased blood flow in the frontal lobe showed significantly more severe impairment of VS., Conclusions: VS may be a useful biomarker to differentiate patients with PSP from those with PD. Cerebellar networks that connect with the cerebral cortex and basal ganglia may contribute to impaired VS of caloric nystagmus in PSP.

We report a case of Broca's aphasia in a left-handed patient with a right brain infarction. The patient's speech is consistent with a particular type of aphemia, that is, without vocalization except for a few phonemes or words. The patient presented with aphonia in an early stage. The lack of speech could be due to the impairment of the phonological-speech process or speech initialization. This type of aphemia has been reported to involve the right inferior precentral gyrus or right middle and inferior frontal gyri. Our patient had both lesions. The symptom and the lesion of this type of aphemia could differ from those of another type of aphemia corresponding to apraxia of speech, and the speech of Broca's aphasia could have multiple mechanisms. Our case shows Alexander's anomalous type with atypical lateralization and distribution of the lesion. Verbal intrahemispheric dissociation apraxia was suspected in our patient. The coexistence of aphasia, anosodiaphoria of hemiplegia is a dual symptom in which bilateral hemispheric functions exist in a unilateral hemisphere. (Received 1 December, 2021; Accepted 1 February, 2022; Published 1 April, 2022).

We herein report a case of myoclonic epilepsy with ragged-red fibers (MERRF) harboring a novel variant in mitochondrial cysteine transfer RNA (MT-TC). A 68-year-old woman presented with progressive myoclonic epilepsy with optic atrophy and peripheral neuropathy. A skin biopsy revealed p62-positive intranuclear inclusions. No mutations were found in the causative genes for diseases known to be related to intranuclear inclusions; however, a novel variant in MT-TC was found. The association between intranuclear inclusions and this newly identified MERRF-associated variant is unclear; however, the rare complication of intranuclear inclusions in a patient with typical MERRF symptoms should be noted for future studies.

Background: The pathogenesis of dystonia is remarkably diverse. Some types of dystonia, such as DYT5 (DYT- GCH1 ) and tardive dystonia, are related to dysfunction of the dopaminergic system. Furthermore, on pathological examination, cell loss in the substantia nigra (SN) of patients with dystonia has been reported, suggesting that impaired dopamine production may be involved in DYT5 and in other types of dystonia. Objectives: To investigate functional dopaminergic impairments, we compared patients with dystonia and those with Parkinson's disease (PD) with normal controls using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and dopamine transporter single photon emission computed tomography (DAT SPECT). Methods: A total of 18, 18, and 27 patients with generalized or segmental dystonia, patients with PD, and healthy controls, respectively, were examined using NM-MRI. The mean area corresponding to NM in the SN (NM-SN) was blindly quantified. DAT SPECT was performed on 17 and eight patients with dystonia and PD, respectively. The imaging data of DAT SPECT were harmonized with the Japanese database using striatum phantom calibration. These imaging data were compared between patients with dystonia or PD and controls from the Japanese database in 256 healthy volunteers using the calibrated specific binding ratio (cSBR). The symptoms of dystonia were evaluated using the Fahn-Marsden Dystonia Rating Scale (FMDRS), and the correlation between the results of imaging data and FMDRS was examined. Results: The mean areas corresponding to NM in the SN (NM-SN) were 31 ± 4.2, 28 ± 3.8, and 43 ± 3.8 pixels in patients with dystonia, PD, and in healthy controls, respectively. The mean cSBRs were 5 ± 0.2, 2.8 ± 0.2, 9.2 (predictive) in patients with dystonia, PD, and in healthy controls, respectively. The NM-SN area ( r = -0.49, p < 0.05) and the cSBR ( r = -0.54, p < 0.05) were inversely correlated with the FMDRS. There was no significant difference between the dystonia and PD groups regarding NM-SN ( p = 0.28). In contrast, the cSBR was lower in patients with PD than in those with dystonia ( p < 0.5 × 10 -6 ). Conclusions: Impairments of the dopaminergic system may be involved in developing generalized and segmental dystonia. SN abnormalities in patients with dystonia were supposed to be different from degeneration in PD., Competing Interests: Unrelated to this study, FY receives grants from InSightec, Ltd. for a trial on focused ultrasound for Parkinson's disease. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ikezawa, Yokochi, Okiyama, Kumada, Tojima, Kamiyama, Hanakawa, Matsuda, Tanaka, Nakata and Isozaki.)

Due to its rarity and the limited literature, the clinicopathological characteristics of peripheral nerve involvement in immunoglobulin G4 (IgG4)-related disease are unknown. We present two cases of IgG4-related disease, accompanied by peripheral neuropathy, presenting as unilateral ptosis (case 1) and sclerosing cholangitis (case 2), respectively. In both cases, sural nerve biopsy indicated vasculitis as the underlying pathophysiology; the peripheral neuropathy was refractory to corticosteroid therapy. In contrast to the previously proposed pathomechanism of IgG4-related neuropathy (direct lymphoplasmacytic infiltration), the pathological findings in our cases suggest that vasculitis occurs secondary to systemic autoimmune conditions.

Introduction: It is unclear whether tau-positive granular glial pathology is a characteristic feature of MSA. We aimed to analyse the prevalence and significance of tau-positive granular glial pathology in MSA., Methods: Fourteen MSA cases were clinicopathologically investigated, focusing on tau-positive granular glial pathology in the frontal and temporal white matter and putamen., Results: In five MSA cases, the temporal white matter showed AT8-positive granular glial pathology; this pathology was detected in the frontal white matter in three cases. AT8-positive granular glia in the white matter were associated with long disease duration with long-term tube feeding and/or long-term tracheotomy. Alpha-synuclein-positive glial cytoplasmic inclusion intensity was not associated with AT8-positive granular glial pathology. The tau isoform of AT8-positive granular glia in the cerebral white matter exhibited three-repeat, not four-repeat, tau. Ten MSA patients showed tau-positive granular glial pathology in the putamen; the tau isoform was predominantly three-repeat tau and four-repeat tau in cases with disease duration ≥13 years and < 13 years, respectively., Conclusions: Tau-positive granular glia in the putamen is a characteristic pathological feature of MSA. Tau-positive granular glia appear in the cerebral white matter in MSA patients and are associated with long disease duration with long-term tube feeding and/or long-term tracheotomy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To investigate the clinical characteristics of children and adults with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis., Methods: Patients who tested positive for the anti-NMDAR antibody (by a cell-based assay) in the cerebrospinal fluid were enrolled. They were divided into two groups based on age (<16 years or older)., Results: Three children (two males and one female) and four adults (one male and three females) were examined. The age at onset was 3.0 ± 1.41 years (range: 2-5 years) for the children and 31.8 ± 6.80 years (range: 20-36 years) for the adults. The follow-up duration was 82.7 ± 23.80 months (range: 52-110 months) for the children and 61.5 ± 12.54 months (range: 43-78 months) for the adults. Prodromal symptoms such as fever and headache were observed in three adults. Two children received influenza vaccination before the onset of encephalitis. Brain magnetic resonance imaging abnormalities were observed in three children and one adult. Basal ganglia lesions were observed in two children and one adult, and the two children showed dystonia. Two children and one adult without neoplasms experienced recurrences. The modified Rankin Scale scores at the final follow-up tended to be worse in children than in adults., Conclusion: Three patients had basal ganglia lesions, and two of them showed dystonia. Dystonia with basal ganglia lesions has been rarely reported in anti-NMDAR encephalitis but should be noted as a significant symptom, which severely affects the activities of daily life., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Competing Interests: The authors have no potential conflicts of interest to disclose.

Progressive supranuclear palsy - Richardson syndrome (PSP-RS) was first described in 1964 by Steele et al. Tau pathology has not been reported in the hypoglossal nuclei of PSP-RS patients, whereas Steele et al. described gliosis with no remarkable neuronal losses in the hypoglossal nucleus. This study aimed to investigate the distribution and degree of tau pathology-associated neurodegeneration, with an emphasis on the hypoglossal nucleus, in patients with PSP-RS. Six clinicopathologically proven PSP-RS cases were included in this study. All patients were clinicopathologically and immunohistochemically re-evaluated. This study confirmed the following neuropathological characteristics of PSP-RS: (1) neurodegeneration usually affects the striatonigral system and cerebellar dentate nucleus; (2) the cerebellar afferent system in PSP-RS is affected by absent-to-mild neurodegeneration; and (3) the extent of tau distribution throughout the central nervous system is greater than the extent of neurodegeneration. Furthermore, we found that subthalamic neurodegeneration was more prominent in the ventromedial region than in the dorsolateral region. Nevertheless, the tau pathology showed no remarkable differences between these two sites. Interestingly, the tau pathology was frequently observed in the hypoglossal nuclei of PSP-RS patients. Gradient neurodegeneration of the subthalamus and tau pathology in the hypoglossal nucleus could be regarded as essential pathological features of PSP-RS., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

We describe a patient with sporadic amyotrophic lateral sclerosis (ALS) who showed progressive deterioration of sensory cortex excitability at the advanced stage, while using invasive ventilation. At the time of diagnosis, the patient showed enlarged N20 of the median nerve somatosensory evoked potential (SEP). Following ventilator use through tracheostomy, the patient gradually fell into a totally locked-in state for four years and the N20 showed progressive deterioration in the amplitude, which finally led to its loss. Magnetic resonance imaging (MRI) showed frontotemporal and mild parietal cortex atrophy, subcortical white matter hyperintensity and brainstem atrophy suggesting the involvement of the central sensory pathways. MRI and flash visual evoked potentials revealed that the occipital lobe was well-preserved throughout the course of the disease. This is the first case report of a physiological demonstration of multisystem neurodegeneration involving the central sensory pathway in a patient with advanced ALS and invasive ventilation use.

Objectives: Fasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas)., Methods: Thirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort., Results: The mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch's t-test)., Conclusion: Small FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS., Significance: Clinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells and the infiltration of CD4 + and CD8 + T cells and plasma cells was also observed. Immunosuppressants were tapered off and mirtazapine and mefloquine administered, resulting in a favorable outcome.

[Background] Supranuclear extraorbital muscle palsy is the core feature of progressive supranuclear palsy (PSP), and ordinarily presents as spontaneous vertical gaze constriction. However, higher visual function associated with visuospatial cognition in PSP patients was not previously considered. [Case presentation] We present a 72-year old right-handed man with PSP- Richardson syndrome (PSP-RS) and abnormal higher visual function. His symptoms began 2 years previously and included the use of small steps while walking, forgetfulness, and postural instability. Neurological examination revealed supranuclear vertical gaze limitation, akinesia, and lead-pipe rigidity without laterality. Neuro-ophthalmological examination showed abnormal ocular movement consistent with PSP, and no visual abnormality was observed. General cognitive functions, including attention and prominent visuospatial orientation and visual attention disturbances, were assessed using neuropsychological tests and concomitant spatial agraphia and impaired configuration using figure copying. Although he presented with mildly decreased and monotonous speech with palilalia, he showed no apparent aphasia, apraxia, visual object agnosia, or Bálint's 'optische Ataxie' i.e. visual ataxia under fixation. Brain MRI revealed atrophy of the mesencephalic tegmentum, bilateral frontal lobe, and bilateral hippocampus. N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography revealed decreased cerebral blood flow in the bilateral frontal lobe, lateral temporal lobe, and basal ganglia. Dopamine transporter single photon emission CT revealed uptake attenuation in the bilateral striatum. 123 I-metaiodobenzyl-guanidine myocardium scintigraphy results were normal. [Discussion] The patient's symptoms indicated classical PSP-RS accompanied with a combination of disturbances in spatial orientation and visual attention as noted by Holmes and Horrax and 'ataxie optique' by Garcin. Thus, as observed in this patient, many clinically diagnosed PSP patients with undiagnosed higher visual dysfunction, masked by limited eye movement may exist. These symptoms may further our understanding about posterior cortical atrophy and tauopathy including not only PSP but also corticobasal syndrome and Alzheimer disease.

Weight loss is an independent predictor of survival in the early stages of amyotrophic lateral sclerosis (ALS). However, the effects of weight variations on the functional prognosis after tracheostomy and invasive ventilation (TIV) in ALS remain unknown. This prospective cohort study aimed to investigate the relationship between weight loss before TIV and disease progression after TIV in ALS patients. Sixty ALS patients with TIV were enrolled and classified into subgroups based on the rate of decline in body mass index, from onset to TIV utilization (ΔBMI). During follow-up, we assessed the patients for presence of communication impairments, ophthalmoplegia, total quadriplegia, mouth opening disability, and dysuria. We analyzed the relationship between ΔBMI and the communication stage or motor disabilities. The log-rank test showed that patients with a ΔBMI ≥ 1.7 kg/m 2 /year showed a shorter period of preserved communication ability (p = 0.0001), shorter time to develop ophthalmoplegia (p = 0.0001), total quadriplegia (p < 0.0001), mouth opening disability (p < 0.0001), and dysuria (p = 0.0455). Cox multivariate analyses showed that a larger ΔBMI was an independent prognostic factor for the early development of ophthalmoplegia (p = 0.0400) and total quadriplegia (p = 0.0445). Weight loss in the early stages of ALS predicts disease progression in patients with advanced stages of ALS using TIV.

Background: Body weight reduction after disease onset is an independent predictor of survival in amyotrophic lateral sclerosis (ALS), but significance of weight variation after diagnosis remains to be established., Objective: To investigate weight variation after diagnosis and its prognostic significance in patients with ALS as a prospective cohort study., Methods: Seventy-nine patients with ALS were enrolled in this study. At the time of diagnosis and about 1 year later, we evaluated the following parameters: age, sex, onset age, onset region, body mass index (BMI) and premorbid BMI, forced vital capacity and the revised ALS functional rating scale. Annual BMI decline rates (∆BMI) from onset to diagnosis and from diagnosis to about 1 year later were calculated. Patients were followed to the endpoints (death or tracheostomy), and the relationships between ∆BMIs and survival were investigated., Results: Patients with post-diagnostic ∆BMI ≥ 2.0 kg/m 2 /year showed shorter survival length than those with < 2.0 kg/m 2 /year (log-rank test, p < 0.0001), and multivariate analysis using the Cox model revealed post-diagnostic ∆BMI as an independent prognostic factor. No correlation was identified between pre- and post-diagnostic ∆BMIs. Female patients with post-diagnostic ∆BMI < pre-diagnostic ∆BMI showed longer survival than those with the opposite ∆BMI trend (log-rank test, p = 0.0147). Female patients with post-diagnostic weight increase showed longer survival than those with weight decrease (log-rank test, p = 0.0228)., Conclusion: Body weight changes after diagnosis strongly predicts survival in ALS, and weight gain after diagnosis may improve survival prognosis, particularly in female ALS patients.

Cardiac involvement in muscular dystrophy (MD) is known to cause heart failure (HF). However, little is known about the differences in electrocardiographic and echocardiographic findings between MD patients with and without the experience of hospitalization for HF. We retrospectively identified 95 MD patients (mean age at diagnosis of MD 41.1 ± 18.7 years; males 64.2%), including nine (9.4%) patients who were hospitalized for HF (the HF group) and 86 (90.6%) patients who were not (the non-HF group) during the follow-up period (16.7 ± 12.2 years). The HF group had a significantly wider QRS duration (126.0 ± 37.6 vs. 98.1 ± 16.7 ms, p < 0.001) and QTc interval (454.6 ± 50.5 vs. 409.5 ± 23.6 ms, p < 0.001) at the time of HF hospitalization than the non-HF group. The HF group also had a significantly lower left ventricular (LV) ejection fraction (35.4 ± 19.2 vs. 62.5 ± 11.3%, p < 0.001) and significantly larger diastolic LV dimension (64 ± 2 vs. 45 ± 1 mm, p < 0.001) and left atrial diameter (38 ± 12 vs. 29 ± 6 mm, p = 0.003) at the time of HF hospitalization than the non-HF group. In the HF group, the QRS duration was significantly wider at the time of HF hospitalization than at the initial electrocardiogram before the development of HF (129.8 ± 30.7 vs. 119.0 ± 33.3 ms, p = 0.018). This study suggests that HF occurs in MD patients with electrocardiographic and echocardiographic abnormalities. Early recognition of abnormal findings during a regular electrocardiographic or echocardiographic follow-up may be useful for identifying cardiac involvement in MD.

Introduction: This study aimed to investigate non-motor manifestations in amyotrophic lateral sclerosis (ALS) patients with tracheostomy and invasive ventilation (TIV) and their relevance to disease progression., Methods: Sixty-seven ALS patients with TIV were enrolled, and followed-up prospectively. The patients were classified at the final evaluation into two subgroups according to the duration of TIV use or disease stage measured by communication impairment. We identified non-motor manifestations and investigated their frequencies and differences across the stages., Results: The non-motor manifestations were macroglossia (22.4%), unstable blood pressure (38.8%), hypothermia (26.9%), dysuria (50.7%), and hyperglycemia (12.1%). These manifestations occurred significantly more frequently in patients with TIV ≥5 years than in patients with TIV <5 years, and more in patients with severe communication impairment than in those with preserved communication ability., Discussion: Non-motor manifestations are observed at a high rate in ALS patients with TIV, and are possibly related to disease progression. Muscle Nerve 57: 735-741, 2018., (© 2017 Wiley Periodicals, Inc.)

Objective: To investigate somatosensory cortex excitability and its relationship to survival prognosis in patients with amyotrophic lateral sclerosis (ALS)., Methods: A total of 145 patients with sporadic ALS and 73 healthy control participants were studied. We recorded compound muscle action potential and sensory nerve action potential of the median nerve and the median nerve somatosensory evoked potential (SEP), and we measured parameters, including onset-to-peak amplitude of N13 and N20 and peak-to-peak amplitude between N20 and P25 (N20p-P25p). Clinical prognostic factors, including ALS Functional Rating Scale-Revised, were evaluated. We followed up patients until the endpoints (death or tracheostomy) and analyzed factors associated with survival using multivariate analysis in the Cox proportional hazard model., Results: Compared to controls, patients with ALS showed a larger amplitude of N20p-P25p in the median nerve SEP. Median survival time after examination was shorter in patients with N20p-P25p ≥8 μV (0.82 years) than in those with N20p-P25p <8 μV (1.68 years, p = 0.0002, log-rank test). Multivariate analysis identified a larger N20p-P25p amplitude as a factor that was independently associated with shorter survival ( p = 0.002)., Conclusion: Sensory cortex hyperexcitability predicts short survival in patients with ALS., (© 2018 American Academy of Neurology.)

Based on the hypothesis that autoimmunity plays a role in the pathogenesis of neuralgic amyotrophy (NA), immunotherapy is sometimes administered. Early intervention is recommended for a good prognosis. We herein report the case of a 55-year-old man who presented with neuralgia, weakness, and muscle atrophy in his right shoulder girdle and upper arm, which progressed for ten months following a marine sports accident. The patient was diagnosed with NA. His neurological deficits gradually improved after several courses of immunotherapy, suggesting that in addition to being effective for treating early-stage disease, immunotherapy may be effective for treating chronic cases.

Previous case reports and studies have shown that anti-myelin-associated glycoprotein (MAG) antibody can be detected in patients with polyneuropathy without any detectable M-protein. Nevertheless, the frequency of and related factors have not yet been adequately investigated. The objectives of this study are to examine the prevalence of anti-MAG antibody in patients with demyelinating neuropathy without M-protein and to determine their clinical characteristics. From January, 2004, to September, 2016, consecutive patients with chronic demyelinating neuropathy were recruited. Anti-MAG antibody presence was tested at the first evaluation. We determined the prevalence of anti-MAG antibody without M-protein among included patients and evaluated the clinical characteristics. A total of 44 patients were included in the present study (12 women; median age at first visit 60 years [interquartile range 47-67 years]; median duration between onset and first visit 9 months [3-26 months]). M-protein was found in eight patients (18%) at the first evaluation. Anti-MAG antibody was present in 2 of remaining 36 (5.6 [95% confidence interval 0-13.0] %) patients without M-protein. Patients with anti-MAG antibody exhibited slowly progressive and distal dominant neuropathy with elevated serum IgM levels and refractory to immunotherapy. There were no differences in clinical features between patients having anti-MAG antibody without M-protein, and those with M-protein. One patient with the anti-MAG antibody showed a delayed appearance of M-protein during a 4-year follow-up after diagnosis. The prevalence of the anti-MAG antibody in chronic demyelinating neuropathy without any detectable M-protein was 5.6%. Anti-MAG antibody may be detectable earlier than M-protein.

Although typical corticobasal syndrome (CBS) presents with asymmetric upper limb symptoms, the prevalence and clinical characteristics of patients with symptoms beginning in other sites are unknown. From January 1997 through April 2016, consecutive patients with CBS who fulfilled the modified Cambridge criteria were recruited. Their medical records were reviewed to determine the body part, where the initial symptoms developed and the clinical characteristics. A total of 24 patients [13 female participants, median age at onset: 64 (IQR 60-74) years, and median duration between onset and evaluation: 38 (17-53) months] met the criteria. The initial symptom involved the unilateral upper limb in 14 cases (58%), unilateral lower limb in five (21%), gait in four (17%), and visual field in one (4%). Over a median of 59 (IQR 40-68) months of follow-up, the duration between the onset and the time for need of assistance in walking was significantly shorter in the patients with lower limb (p = 0.018 with log-rank test) or gait (p = 0.025) onset than in those with upper limb onset. About a half of the CBS patients initially complained of symptoms other than the upper limb. The most common area of origin of the initial symptom after the upper limb was the lower limb followed by gait. Such patients need assistance in walking earlier than those with upper limb-onset CBS. Patients with lower limb- or gait-onset CBS are not rare and may have unfavorable outcome.

This study aimed to quantitatively analyze fasciculation potentials (FPs) and to investigate their relationship with muscle strength in amyotrophic lateral sclerosis (ALS). Fifty-one patients with sporadic ALS or progressive muscular atrophy (25 men, 26 women, mean age of 68 years) underwent needle EMG. We determined the duration, phase number, and amplitude of FPs from three muscles (upper trapezius, biceps brachii, and tibialis anterior) and examined their relations with muscle strength. In total, 878 FPs were analyzed. FP duration displayed a significant negative relation with the strength of all three muscles; the weaker muscles showed longer durations of FPs than the muscles with normal strength. The amplitude and phase number were not related with muscle strength, but there were significant correlations between the duration and amplitude of FPs in the trapezius and tibialis anterior muscles. The longer duration of FPs in muscles with weak strength suggests that the morphological changes of FPs were caused by temporal dispersion through progressively degenerating and/or immature reinnervating motor branches, and were observed uniformly in different muscles along with disease progression.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy-proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA-D). Compared with MSA cases without dementia, MSA-D cases had frequent globular NCIs (G-NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA-D cases could be divided into two types; MSA-D with distinct fronto-temporal lobar degeneration (FTLD type) and without distinct fronto-temporal lobar degeneration (non-FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G-NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA-D, even when a case with MSA-D reveals no significant cerebral atrophy., (© 2016 Japanese Society of Neuropathology.)