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Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. Previously, autonomic symptoms or dysfunction have not been reported. To evaluate subclinical autonomic dysfunction regarding thermoregulatory function in SCA, we recorded sympathetic outflow to skin in a DRPLA patient confirmed by genetic analysis. We recorded skin sympathetic nerve activity (SSNA), which was elicited and recorded by using the microneurographical technique. In results, the resting frequency of SSNA bursts was very low (8.2 ± 0.4 bursts/min [institutional normal range: 20.8 ± 2.4 bursts/min]). However, acceleration of SSNA bursts induced by mental arithmetic stress was confirmed. The amplitude of reflex bursts induced by electrical stimuli was slightly low (9.6 ± 1.6 μV [institutional normal range: 10.9 ± 2.2 μV]), and the reflex latency was mildly prolonged (872 ± 23.7 msec [institutional normal range: 761.9 ± 51.7 msec]). These results suggest potentially central autonomic dysfunction in this patient with DRPLA. To our knowledge, this is the first report to record SSNA and confirm subclinical autonomic dysfunction in a case with DRPLA.

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYST is responsible for Chediak-Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYST mutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYST mutations in HSP, finding six adult patients with LYST mutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYST mutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.

We report here a rare case of adult-onset multiloculated hydrocephalus (MLH) after Cryptococcal meningitis. A 63-year-old man had Cryptococcal ventriculitis in 2011, and he recovered with treatment of antimycotic drugs. However, he was admitted again because of disorientation and amnesia, and brain MRI showed dilation of the inferior horn of the left lateral ventricle. He underwent a ventriculoperitoneal shunt (VPS) for noncommunicating hydrocephalus in 2019, and the disorientation and amnesia improved. One year after the VPS, he was admitted because of urinary dysfunction and gait disturbance. Brain MRI showed dilation of the bilateral anterior horns of the lateral ventricles. He underwent an additional VPS into the space in 2020, and urinary dysfunction and gait disturbance improved. This case was supposed that the symptom in agreement with the dilated ventricle by MLH was shown.

This study evaluated yearly changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rates (HR) for patients with Parkinson's disease (PD). Data were collected for the last 10 years from medical records of 28 PD patients and 30 non-PD patients with other neurological disorders. Age-related changes in each group were analyzed by year using mean values of SBP, DBP, and HR obtained at their bi-monthly visits. In results, PD patients had a gradual decrease in SBP with longer disease duration, and mean SBP significantly decreased from Year 7-11 compared to the mean values for Year 1 (p < .001 or p < .01). In non-PD patients, mean SBP significantly increased from Year 4-11 compared to the mean values for Year 1 (p < .001 or p < .01). This is the first study to report age-related changes of BP in individual patients with PD over 10 years.

Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.

SPG5 is a rare subtype of autosomal recessive hereditary spastic paraplegia caused by a homozygous mutation in the oxysterol 7α-hydroxylase gene, CYP7B1. We describe the first Japanese patient with SPG5 with a novel mutation in the CYP7B1 gene. On exome sequencing, we identified a homozygous frameshift mutation, c.741delA, p.K247fs, in exon 3 of the CYP7B1 gene. The patient showed spastic paraparesis with white matter hyperintensities in the bilateral corona radiata and periventricular and subcortical regions on brain magnetic resonance imaging. The present study expands the mutation spectrum of CYP7B1 and provides an opportunity to study the genotype-phenotype correlation in SPG5.

We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. Brain magnetic resonance imaging showed mild cerebral atrophy and linear hyperintensities at the corticomedullary junction on diffusion-weighted images. This patient developed nonconvulsive status epilepticus with generalized periodic discharges on electroencephalography after recurrent symptoms of paroxysmal nausea and slowly progressive cognitive decline. There have been no previous reports of NIID with nonconvulsive status epilepticus to our knowledge. Since adult patients with NIID display a wide variety of clinical manifestations, skin biopsy should be considered in patients who have leukoencephalopathy of unknown origin., Highlights • We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. • This patient developed non-convulsive status epilepticus with generalized periodic discharge on electroencephalography. • Since adult patients with neuronal NIID display a wide variety of clinical manifestations, skin biopsy should be recommended in patients who have leukoencephalopathy of unknown origin.

A 35-year-old male was admitted to our hospital because of suspected myelitis. T2-weighted spinal MRI revealed a high intensity area at Th7-9. On admission, he showed mild weakness of the lower extremities and hyperreflexia of all extremities. Therefore, he was diagnosed with having spastic paraplegia. He presented no trismus or opisthotonos. There was pleocytosis in the cerebral spinal fluid. Dysuria, constipation and spasticity of the bilateral legs worsened, even though we administered methylprednisolone pulse therapy. Nonetheless, the symptoms had progressed on the 11th hospital day, opisthotonus and optic hyperesthesia were presented. On the 13th hospital day, we suspected local tetanus and administered tetanus toxoid. After one month, his symptoms had gradually improved. In the case of spastic paraplegia showing a subacute progression course and a faint abnormality on spinal MRI, the possibility of local tetanus should be considered.

To find out the physiological method for evaluating the severity of central autonomic dysfunction, we performed detailed evaluation of cutaneous vasomotor neural function in a comparatively large sample of multiple system atrophy (MSA). We evaluated cutaneous vasomotor neural function in 24 MSA patients. Skin sympathetic nerve activity (SSNA) and sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex [SVR]) were recorded at rest, as well as reflex changes after electrical stimulation. The parameters investigated were SSNA frequency at rest, reflex latency and amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and spontaneous SVR and SSR frequency. There were negative correlations between resting SSNA and disease duration or the SCOPA-AUT score, but these were not significant. SSNA reflex latency displayed significant positive correlations with disease duration and SCOPA-AUT score (p

Background Non-dystrophic myotonias (NDMs) are skeletal muscle disorders involving myotonia distinct from myotonic dystrophy. It has been reported that the muscle pathology is usually normal or comprises mild myopathic changes in NDMs. We describe various pathological findings mimicking those of myotonic dystrophy (DM) in biopsied muscle specimens from a patient with NDMs with a long disease duration. Case presentation A 66-year-old Japanease man presented eye closure myotonia, percussion myotonia and grip myotonia together with the warm-up phenomenon and cold aggravation from early childhood. On genetic analysis, a heterozygous mutation of the SCN4A gene (c.2065 C > T, p.L689F), with no mutation of the CLCN1, DMPK, or ZNF9/CNBP gene, was detected. He was diagnosed as having NDMs. A biopsy of the biceps brachii muscle showed increasing fiber size variation, internal nuclei, chained nuclei, necrotic fibers, fiber splitting, endomysial fibrosis, pyknotic nuclear clumps and disorganized intermyofibrillar networks. Sarcoplasmic masses, tubular aggregates and ragged-red fibers were absent. Conclusion It is noteworthy that the present study revealed various pathological findings resembling those seen in DM, although the pathology is usually normal or mild in NDMs. The pathological similarities may be due to muscular modification with long-standing myotonia or excessive muscle contraction based on abnormal channel activity. Electronic supplementary material The online version of this article (10.1186/s12883-019-1360-0) contains supplementary material, which is available to authorized users.

Neuronal intranuclear inclusion disease (NIID) has highly variable clinical manifestations. Sone et al. describe the clinical and pathological features of 57 adult-onset cases diagnosed by postmortem dissection/antemortem skin biopsy. They report ‘dementia dominant’ and ‘limb weakness’ subtypes, and recommend consideration of NIID in the differential diagnosis of leukoencephalopathy and neuropathy., Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated ‘dementia dominant group’, followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated ‘limb weakness group’, followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.

Introduction Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA. Methods We performed [123I] FP-CIT SPECT and [123I] N-isopropyl-p-iodoamphetamine SPECT (IMP-SPECT), and determined GBA expression and glucocerebrosidase (GCase) activity in leukocytes in two GBA-associated PD patients and nine unaffected individuals (including four mutation carriers) in a Japanese family with a heterozygous gross deletion mutation in the GBA gene. Results The two PD patients and two of the four clinically unaffected carriers showed decreased [123I] FP-CIT uptake. IMP-SPECT showed a pattern like that in DLB in one patient. When we compared PD patients with GBA mutations with clinically unaffected carriers, there was a poor correlation between the development of PD and the expression level of GBA or GCase activity. Conclusion We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [123I] FP-CIT in this family. However, since we cannot conclude whether a reduction of GCase activity is directly correlated with the pathogenesis of PD or not, longitudinal follow-up of this family is needed.

A 33-year-old woman was admitted due to disturbance of consciousness, dysarthria, dysphagia, sensory disturbances and weakness of the left upper limb after mycoplasma infection. She was treated with intravenous immunoglobulin and intravenous high-dose methylprednisolone as Bickerstaff brainstem encephalitis (BBE). On the 15th hospital day, reflex myoclonus appeared on her face, neck, body and limbs induced by techniques of jaw jerk reflex and patellar tendon reflex. The myoclonus was disappeared after two weeks in accordance with improvement of BBE. The transient reflex myoclonus may be originated from brainstem lesion which was affected by BBE. Reflex myoclonus is thought to be rare symptom in patient with BBE.

The detailed pathophysiology of limb coldness in multiple system atrophy (MSA) is unknown.We evaluated cutaneous vasomotor neural function in 18 MSA patients with or without limb coldness, and in 20 healthy volunteers as controls. We measured resting skin sympathetic nerve activity (SSNA) and spontaneous changes of the sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex: SVR), as well as SVR and reflex changes of SSNA after electrical stimulation. The parameters investigated were the SSNA frequency at rest, amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and skin blood flow velocity.Both the resting frequency of SSNA and the amplitude of SSNA reflex bursts were significantly lower in the MSA group than the control group (p0.001 and p0.05, respectively). There were no significant differences between the two groups with regard to the absolute decrease or percent reduction of SVR volume. The recovery time showed no significant difference between all MSA patients and control groups, but it was significantly prolonged in six MSA patients with limb coldness compared with that in the control group and that in MSA patients without limb coldness (p0.01). The skin blood flow velocity was significantly slower in the MSA group than in the control group (p0.001).In MSA patients, limb coldness might occur due to impairments of the peripheral circulation based on prolongation of vasoconstriction and a decrease of skin blood flow velocity secondary to combined pre- and postganglionic skin vasomotor dysfunction.

To investigate the vasomotor regulation in multiple system atrophy (MSA), we simultaneously recorded muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure in 14 MSA patients without syncope and 18 healthy subjects. Resting MSNA bursts were significantly less frequent in MSA patients than healthy subjects (p

We recorded skin sympathetic nerve activity (SSNA), SSR, and SVR in 30 subjects. SSNA and SVR showed a slight decrease and spontaneous changes in resting SSR were significantly less frequent in older subjects compared with younger subjects (p

Metronidazole-induced encephalopathy (MIE) is a rare clinical condition resulting from long-term use of metronidazole. The symptoms and brain MRI changes in MIE usually resolve dramatically on discontinuation of treatment, and thus MIE with brain cystic lesions has rarely been reported. A 49-year-old woman was treated for a lumbar abscess with oral administration of 1.5 g/day of metronidazole for 4 months. Neurological examination revealed aphasia, apraxia, agraphia, cerebellar ataxia, and cognitive impairment. On brain MRI, diffusion-weighted imaging and the apparent diffusion coefficients were consistent with cytotoxic edema in the corpus callosum and subcortical white matter, representing delayed huge cystic lesions. Thus, we should be aware of MIE with irreversible brain lesions.

In amyotrophic lateral sclerosis (ALS), not only impairment of motor neurons but also impairment of the autonomic nervous system has been demonstrated by previous physiological studies. Several investigators have reported a correlation between autonomic dysfunction and respiratory dysfunction in ALS. This study analyzed the relation between parameters of respiratory function and muscle sympathetic nerve activity (MSNA) in a large number of ALS patients.In 50 patients with ALS (mean age (SD): 62.1 (11.7) years), MSNA, heart rate (HR), and blood pressure (BP) were recorded simultaneously. The arterial oxygen content (PaO2), arterial carbon dioxide content (PaCO2), and forced vital capacity expressed as a percentage of the predicted value for healthy controls (%VC) were determined as parameters of respiratory function.There were no significant correlations between MSNA and PaO2, PaCO2, %VC, or the disability score. Analysis of chronological changes in 14 patients examined twice showed that the disability score and PaCO2 were significantly increased, and %VC was significantly more decreased at the second examination compared with the first examination (p0.01 and p0.05, respectively). In contrast, HR, BP, burst rate of MSNA, and age-adjusted MSNA exhibited no significant changes between the first and second examinations.These findings show that gradual deterioration of respiratory function in ALS patients is not associated with changes of quantitative MSNA parameters, which may suggest that abnormality of the autonomic nervous system is a primary feature of ALS.

Usefulness of bronchoalveolar lavage fluid (BALF) and pleural cavity lavage fluid (PLF) as an experimental material was evaluated for the assessment of pulmonary toxicity of chemicals in rats. From the viewpoint of safety, isoflurane can be used for euthanasia/anesthesia because there was no difference in biological properties of BALF between diethyl ether and isoflurane. Here, we also recognized phosphate buffered saline (PBS) and distilled water equally as a solvent/vehicle for negative control. PLF is also provided as a useful target material as well as BALF for assessing chemical lung toxicity. To evaluate the method, we used zinc chloride as a model chemical and obtained the expected and satisfied results. We may conclude that the intratracheal treatment and combination usage of BALF and PLF as a target material is a good method for assessment of chemical pulmonary (lung and plural cavity) toxicity in rats.