Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder.

Objective: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD). Methods: Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021. Results: Of the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0 vs. 34.9%, P = 0.008), whereas involuntary movements were significantly less prevalent (31.3 vs. 69.8%, P = 0.007), among anti-gAChR antibody-positive compared with -negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed. Conclusions: An autoimmune mechanism mediated by anti-gAChR antibodies may be involved in disease etiology in a subgroup of FNSD/CD patients.

The application of shotgun metagenomics to the diagnosis of granulomatous amoebic encephalitis due to Balamuthia mandrillaris: a case report.

BACKGROUND: Granulomatous amoebic encephalitis (GAE) is an infrequent and fatal infectious disease worldwide. Antemortem diagnosis in this condition is very difficult because clinical manifestations and neuroimaging are nonspecific. CASE PRESENTATION: A 60-year-old Japanese woman was admitted with a chief complaint of left homonymous hemianopsia. Brain-MRI showed extensive necrotizing lesions enhanced by gadolinium, in the right frontal lobe, right occipital lobe, and left parietal lobe. Epithelioid granulomas of unknown etiology were found in the biopsied brain specimens. Shotgun metagenomic sequencing using a next-generation sequencer detected DNA fragments of Balamuthia mandrillaris in the tissue specimens. The diagnosis of granulomatous amoebic encephalitis was confirmed using an amoeba-specific polymerase chain reaction and immunostaining on the biopsied tissues. CONCLUSIONS: Shotgun metagenomics is useful for the diagnosis of central nervous system infections such as GAE wherein the pathogens are difficult to identify.

Correlation between clinical and radiologic features of patients with Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu).

BACKGROUND AND PURPOSE: Gerstmann-Sträussler-Scheinker syndrome is a rare hereditary neurodegenerative disorder with clinical heterogeneity. This study is aim to demonstrate the clinical spectrum and radiologic characteristics of patients caused by Pro102Leu mutation in PRNP. MATERIALS AND METHODS: We retrospect clinical manifestations of five patients from four Japanese families, and comprehensively analyzed their brain MRI, SPECT (N-isopropyl-p-[123I] iodoamphetamine), and PET (18F-2-fluoro-2-deoxy-d-glucose) images. RESULTS: All patients developed ataxia of lower limbs and trunk, gait disturbance, dysesthesia in legs, and lower limb hyporeflexia. In the early clinical stage before dementia began, no noticeable abnormalities could be observed from brain MRI, but SPECT and PET revealed mosaic-like pattern of blood flow and glucose metabolism of the brain. Predominant abnormalities were found in the occipital and frontal lobes on SPECT and PET analysis, respectively. In SPECT analysis, blood flow of the anterior cerebellar lobes was lower than that of the posterior cerebellar lobes. CONCLUSIONS: Clinical symptoms resulting from failure of dorsal horn of spinal cord and spinocerebellar tracts were observed in all cases. Radiologic findings revealed individual differences of involved region in their brain, which could produce clinical diversity. We identified a downtrend of blood flow in the anterior cerebellar lobes, a projection field of the spinocerebellar tracts, which is an important feature of Gerstmann-Sträussler-Scheinker syndrome.

Toxocara canis myelitis involving the lumbosacral region: a case report.

CONTEXT: Toxocara canis is a parasite known to cause visceral larva migrans. The infection rarely affects the central nervous system but there have been several reports of myelitis caused by visceral larva migrans due to Toxocara canis. In previous reported cases, the lesions were located in the thoracic or cervical spinal cord. To the best of our knowledge, this is the first report of a lesion involving the lumbosacral region. FINDINGS: A 60-year-old man developed weakness and dysesthesia in the lower limbs. The symptoms resolved spontaneously, but recurred after five months. One month later, the patient developed pollakiuria and constipation. He was a dog owner and frequently ate raw chicken meat and beef liver. Sagittal T2-weighted image (T2WI) showed swelling and hyperintensity in the spinal cord from T10 to the lumbosacral region and focal nodular enhancement on the posterior segment of the lumbar spinal cord. Blood cell counts showed slight eosinophilia and elevated serum immunoglobulin E level. Cerebrospinal fluid examination showed slight pleocytosis with eosinophilia. Enzyme-linked immunosorbent assay showed high levels of anti-Toxocara antibodies in the serum and cerebrospinal fluid. In addition, confirmatory test by Western blot was positive. The patient was initially treated with intravenous methylprednisolone with slight improvement in muscle weakness. Albendazole was added with a second course of intravenous methylprednisolone. The muscle weakness in the lower limbs improved considerably, and swelling and hyperintensity on T2WI almost disappeared. CONCLUSION: Our results suggest that Toxocara canis myelitis cannot be discounted even if the myelitis involves the lumbosacral region.

New type of encephalomyelitis responsive to trimethoprim/sulfamethoxazole treatment in Japan.

OBJECTIVE: To determine the causative pathogen and investigate the effective treatment of a new type of encephalomyelitis with an unknown pathogen in Japan and report the preliminary ultrastructural and genomic characterization of the causative agent. METHODS: From 2005 to 2012, we treated 4 Japanese patients with geographic clustering and comparable clinical features, serum/CSF cytology, and radiologic findings. Brain biopsy was conducted in all patients to analyze neuropathologic changes by histology, and electron microscopy was applied to reveal the features of the putative pathogen. Genomic DNA was obtained from the affected brain tissues and CSF, and an unbiased high-throughput sequencing approach was used to screen for specific genomic sequences indicative of the pathogen origin. RESULTS: All patients exhibited progressive dementia with involuntary tongue movements. Cytologic examination of CSF revealed elevated mononuclear cells. Abnormal MRI signals were observed in temporal lobes, subcortical white matter, and spinal cord. Biopsied brain tissue exhibited aggregated periodic acid-Schiff-positive macrophages and 2-7 µm diameter round/oval bodies without nuclei or cell walls scattered around the vessels. Unbiased high-throughput sequencing identified more than 100 archaea-specific DNA fragments. All patients were responsive to trimethoprim/sulfamethoxazole (TMP-SMX) plus corticosteroid therapy. CONCLUSIONS: We report 4 cases of encephalomyelitis due to an unknown pathogen. On the basis of ultrastructural and genomic studies, we propose a new disease entity resulting from a causative pathogen having archaeal features. TMP-SMX therapy was effective against this new type of encephalomyelitis.

Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs.

To identify novel mutations causing hereditary motor and sensory neuropathy (HMSN) with pyramidal signs, a variant of Charcot-Marie-Tooth disease (CMT), we screened 28 CMT and related genes in four members of an affected Japanese family. Clinical features included weakness of distal lower limb muscles, foot deformity, and mild sensory loss, then late onset of progressive spasticity. Electrophysiological studies revealed widespread neuropathy. Electron microscopic analysis showed abnormal mitochondria and mitochondrial accumulation in the neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an abnormally thin corpus callosum. In all four, microarrays detected a novel heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light-chain neurofilament protein (NEFL), indicating that NEFL mutations can result in a HMSN with pyramidal signs phenotype.

[Anti-aquaporin-4 antibody autoimmune syndrome with disturbance of consciousness, respiratory failure, and ophthalmoplegia associated with extensive brain stem involvement with intractable hiccup and nausea as an initial manifestation. A case report].

A 45-year-old female was positive for anti-aquaporin-4 antibody with disturbance of consciousness, respiratory failure, and ophthalmoplegia associated with extensive brain stem involvement with intractable hiccup and nausea as an initial manifestation. Her level of consciousness and state of respiration worsened approximately one month later. There was no abnormality in the cerebrospinal fluid examination. A lesion was found in the medullary tegmentum on brain MRI. The patient received steroid pulse therapy and her level of consciousness improved the next day. However, her state of respiration worsened, and she had extensively clinical involvement of the brain stem. Her symptoms gradually improved with intravenous administration of prednisolone and intravenous immunoglobulin therapy (IVIg). The patient had almost completely recovered, but she relapsed with cervical myelitis extending over 3 vertebral segments approximately 10 months later. She underwent steroid pulse therapy, oral prednisolone, and IVIg again and improved.

[Familial prion disease (GSS, familial CJD, FFI)].

We described clinically features of inherited prion disease (GSS, familial CJD and FFI). In addition, we found new useful findings of GSS patients for early diagnosis. Generally, clinicians believe that the main features of GSS (P102L) are cerebellar symptoms and dementia; however, our patients showed other features. Most showed mild gait disturbance, dysesthesia and hyporeflexia of the lower legs, proximal leg muscle weakness, and truncal ataxia during the early stage of the disease. Dementia was not a main symptom during the early stage. The key features for the early diagnosis of GSS102 are truncal ataxia, dysesthesia and hyporeflexia of the lower legs, and mild dysarthria. Normal cerebellar MRI and abnormal cerebral SPECT findings should be useful for early diagnosis of GSS (P102L).

Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in Japanese families.

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. To date, at least 11 genes and 13 additional loci have been identified in ADCAs. Despite phenotypic differences, spinocerebellar ataxia 4 (SCA4) and Japanese 16q-linked ADCA type III map to the same region of 16q22.1. We report four Japanese families with pure cerebellar ataxia and a disease locus at 16q22.1. Our families yielded a peak lod score of 6.01 at marker D16S3141. To refine the candidate region, we carried out genetic linkage studies in four pedigrees with a high density set of DNA markers from chromosome 16q22.1. Our linkage data suggest that the disease locus for 16q-ADCA type III is within the 1.25-Mb interval delineated by markers 17msm and CTTT01. We screened for mutations in 36 genes within the critical region. Our critical region lies within the linkage interval reported for SCA4 and for Japanese 16q-ADCA type III. These data suggest that the ADCA that we have characterized is allelic with SCA4 and Japanese 16q-linked ADCA type III.

Clinical and pathological studies of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R mutation in large Japanese families.

We clarified the clinical and pathological aspects of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R heterozygous mutation in the Miyakonojo Basin, a region in southern Japan where the prevalence of ALS is 11.4 per 10(5) of the population. We studied 17 patients, including one autopsy case, in three FALS families with the mutation. The average age at disease onset in the families was 44.3+/-8.7 years, and the mean disease duration was 12+/-7.6 years, with a range of 6 to 30 years. Ten of 17 patients were unable to walk by the mean age of 56.4+/-12.2 years. The initial symptom was muscle weakness in the distal leg muscle in all patients. The autopsy findings of one FALS patient showed atrophy of lateral and anterior funiculi, decreased numbers of anterior horn cells, preserved posterior funiculus and absence of neuronal inclusion bodies. Percentages of mutant SOD1 protein measured by mass spectrometry were 14% in erythrocytes, 43% in the spinal cord, 47% in the iliopsoas muscle and 60% in the diaphragm. In this study, we confirmed that FALS with SOD1 H46R mutation showed uniform initial symptoms and slow disease progression with intra-familial variation of disease severity and that inclusion body formation is not essential in FALS with this mutation.