A Case of Anti-IgLON5 Disease Showing an Improvement in Dysautonomia, Including Vocal Cord Palsy, via Combined Immunotherapy.

Anti-IgLON5 disease shows various neurological manifestations, of which dysautonomia is one of the major symptoms and is rarely improved by immunotherapy. We herein report a patient with anti-IgLON5 disease who showed several autonomic failures, including vocal cord palsy for four months. The patient presented with cognitive impairments, bulbar symptoms accompanied by myorhythmia in the pharynx and tongue, cerebellar ataxia with tremor, motor neuron symptoms in the limbs, gastrointestinal dysfunction, orthostatic hypotension, non-rapid eye movement sleep disorder on polysomnography, and severe vocal cord palsy. Combined immunotherapy improved his symptoms, including vocal cord palsy, suggesting that combined immunotherapy might improve dysautonomia in anti-IgLON5 disease.

Paraneoplastic Cerebellar Degeneration Accompanied by Seropositivity for Anti-GAD65, Anti-SOX-1 and Anti-VGCC Antibodies Due to Small-cell Lung Cancer.

Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic neurological syndrome that is rarely accompanied by seropositivity with a combination of multiple antibodies. We herein report a 50-year-old man with PCD accompanied by small-cell lung cancer (SCLC). This patient was seropositive for anti-glutamic acid decarboxylase 65, anti-SRY-related HMG-box gene 1 and anti-voltage-gated calcium channel antibodies. After chemoradiation therapy without immunotherapy, cerebellar ataxia of the trunk and limbs markedly improved, along with a notable amelioration of SCLC. This case suggests that tumor therapy should be started immediately and that a panel of anti-neuronal antibodies should be evaluated when PCD with SCLC is suspected.

A Case with Anti-ganglioside Antibodies Showing Multiple Cranial Nerve Palsies Detected on Gadolinium-enhanced Magnetic Resonance Imaging.

The anti-GQ1b IgG antibody is often accompanied by other anti-ganglioside antibodies, which induces various neurological symptoms. We herein report a patient with anti-ganglioside antibodies, including anti-GQ1b IgG and anti-GT1a IgG antibodies, showing bilateral ophthalmoplegia, facial nerve palsies, dysarthria, dysphagia, dysesthesia in both hands, and enhancement of the bilateral oculomotor, abducens, and facial nerves on gadolinium (Gd)-enhanced T1-weighted brain magnetic resonance imaging (MRI). He was first treated with intravenous immunoglobulin, which improved ophthalmoplegia, bulbar palsies, and dysesthesia of hands, but the facial nerve palsies worsened, and Gd enhancement of the brain nerves persisted. High-dose methylprednisolone therapy subsequently improved the facial nerve palsies and Gd enhancement of the cranial nerves. This is the first case with anti-ganglioside antibodies presenting with multiple cranial nerve palsies that was followed to track the changes in the Gd enhancement of cranial nerves on MRI.

Prevalence and development of idiopathic normal pressure hydrocephalus: A 16-year longitudinal study in Japan.

OBJECTIVE: We previously investigated the preclinical state of idiopathic normal pressure hydrocephalus (iNPH): asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging (AVIM) found in community inhabitants. The aim of the study was to determine how iNPH develops longitudinally. MATERIALS AND METHODS: A previous longitudinal prospective community-based cohort study was initiated in 2000. The 271 70 year-old participants were followed up in 2016 at the age of 86 years. At this time, 104 participants could be reached for clinical examinations and brain magnetic resonance imaging (MRI). iNPH in this study was diagnosed if the participant had more than one symptom in the clinical triad and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on MRI, fulfilling at least an Evans index >0.3 (ventricular enlargement, VE) and a narrowing of the subarachnoid space at the high convexity (tight high convexity, THC). Asymptomatic VE (AVE) plus THC were considered AVIM. RESULTS: Longitudinally throughout 16 years, 11 patients with iNPH were found. The hospital consultation rate was only 9%. Five of the eight patients with AVIM (62.5%) and six of 30 with AVE (20.0%) developed iNPH. Cross-sectionally, eight patients had iNPH (8/104, 7.7% prevalence at the age of 86) in 2016. Disease development was classified into THC-preceding and VE-preceding iNPH. One VE-preceding iNPH case was considered a comorbidity of Alzheimer's dementia. CONCLUSION: Idiopathic normal pressure hydrocephalus had a high prevalence among octogenarians in the evaluated community. iNPH developed not only via AVIM but also via AVE, the latter was also frequent in the elderly.

Differing clinical features between Japanese siblings with cerebrotendinous xanthomatosis with a novel compound heterozygous CYP27A1 mutation: a case report.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive lipid storage disorder caused by mutations in the CYP27A1 gene encoding the key enzyme in the bile acid synthesis, sterol 27-hydroxylase. Here, we report two Japanese CTX siblings with a novel compound heterozygous CYP27A1 mutation, showing different clinical phenotypes and responses to chenodeoxycholic acid (CDCA) therapy. CASE PRESENTATION: The proband, a 32-year-old man, who had chronic diarrhea, bilateral cataracts, and xanthomas, demonstrated progressive neurological manifestations including ataxia, and spastic paraplegia during a 5-year follow-up period despite normalization of serum cholestanol after initiation of CDCA treatment. He also exhibited cognitive decline although improvement had been observed at the beginning of treatment. Follow-up brain magnetic resonance imaging (MRI) revealed pronounced progressive atrophy in the cerebellum, in addition to expanding hyperintense lesions in the dentate nuclei, posterior limb of the internal capsule, cerebral peduncles, and inferior olives on T2-weighted images. In contrast, the two-year-younger sister of the proband presented with chronic diarrhea, cataracts, xanthomas, and intellectual disability but no other neurological symptoms at the time of diagnosis. CDCA treatment lead to improvement of cognitive function and there were no characteristic CTX-related MRI features during the follow-up period. The siblings shared a paternally inherited c.1420C > T mutation (p.Arg474Trp) and a maternally inherited novel c.1176_1177delGA mutation, predicting p.(Glu392Asp*20). CONCLUSIONS: Our cases suggest that early diagnosis and subsequent initiation of CDCA treatment are crucial before the appearance of characteristic MRI findings and severe neurological manifestations related to CTX. Further studies are required to elucidate mechanisms responsible for the clinical diversity of CTX and prognostic factors for long-term outcomes following initiation of CDCA treatment.

Reduced cerebral blood flow of lingual gyrus associated with both cognitive impairment and gait disturbance in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is primarily characterized by cognitive impairment and gait disturbance. Our objective was to evaluate the clinical characteristics of iNPH and the association between cerebral blood flow (CBF), measured using single-photon emission computed tomography (SPECT), and both cognitive and gait disturbances in iNPH patients. METHODS: We compared cognitive and motor functions and neuroimaging findings between 29 iNPH patients and 35 age-matched Parkinson's disease (PD) patients. We examined the associations between cognitive and motor dysfunctions and CBF in iNPH patients using 99mTc-ECD SPECT subtraction imaging data from a database of healthy control subjects. RESULTS: The cognitive function of iNPH patients, as measured by the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB), was significantly poorer than that of PD patients; however motor function of the legs based on the Unified PD Rating Scale (UPDRS) part III was similar across groups. Impairment in cognitive function based on the MMSE and FAB was significantly correlated with motor dysfunction of the legs on the UPDRS part III and the 3-m Timed Up and Go test. Furthermore, 99mTc-ECD SPECT subtraction imaging revealed lower CBF in the bilateral lingual gyrus of iNPH patients with severely impaired cognitive and motor functions than healthy control subjects. CONCLUSION: Patients with iNPH have severely impaired cognitive function; however, motor dysfunction of the legs is similar to PD patients. The cognitive and gait disturbances of iNPH are significantly interrelated, which may be associated with an impaired brain network that includes the bilateral lingual gyrus.

[Recurrent ataxia and respiratory failure with probable paraneoplastic syndrome responsive to plasma exchange therapy].

An 80-year-old male with prostatic adenocarcinoma who was treated with orchiectomy presented dysarthria and difficulty in walking. His symptoms subacutely progressed. Seven days later, he was non-ambulatory and was admitted to our hospital. He had poor vision and cerebellar ataxia of the lower extremities; however, his muscle strength, tendon reflexes, and sensory functions were preserved. Paraneoplastic retinopathy was diagnosed based on electroretinographic and visual field defect. Further, brain and spinal MRI, cerebral spinal fluid, and nerve conduction assessments were normal. These symptoms were followed by consciousness disturbance and respiratory failure; consequently, he required non-invasive positive pressure ventilation (NPPV) and tube feeding. Steroid pulse therapy and plasma exchange (PE) were performed. In response to the therapy, all these symptoms were relieved, and NPPV and tube feeding were withdrawn. However, the same symptoms occurred additional three times throughout the course of approximately 1 year. Each time, PE was the most effective treatment. Although paraneoplastic neurological syndrome associated with prostatic cancer is rare, immunotherapy could be a therapeutic choice to relive symptoms.

Tooth Loss-associated Cognitive Impairment in the Elderly: A Community-based Study in Japan.

Objective Dementia is a major cause of disruption for a healthy life expectancy in Japan. It has been suggested that the number of teeth is a modifiable risk factor for cognitive impairment and dementia. We therefore examined the possible association between the cognitive function and the number of natural and artificial teeth in community-dwelling Japanese elderly individuals. Methods Among the participants in our prospective, community-based study, 210 elderly individuals (103 men and 107 women; 78.1±4.9 years; mean age±standard deviation) underwent both dental examinations and a Mini-Mental State Examination (MMSE), as well as various medical checkups, in 2016 and 2017. Results The number of natural teeth was significantly associated with an individual's MMSE score. The percentage of cognitively normal subjects (MMSE scores: 27-30) decreased significantly with a decrease in the number of natural teeth. Among the MMSE items, the calculation ability was significantly and independently associated with the number of natural teeth. Regression was calculated as the predicted score of MMSE =21+0.3× (years of schooling) +0.1× (number of natural teeth). Among individuals with 19 or fewer natural teeth, those who had a total of 20 teeth or more, including both natural and artificial teeth, had significantly higher MMSE scores than those who had 19 or fewer natural and artificial teeth combined. Conclusion The number of natural teeth was significantly associated with the cognitive function, especially the calculation ability, and the use of artificial teeth was associated with the preservation of the cognitive function in community-dwelling elderly individuals.

Cognitive impairment, brain ischemia and shorter telomeres are predictors of mortality in the Japanese elderly: A 13-year prospective community-based study.

OBJECTIVE: To examine whether cognitive impairment, deep white matter hyperintensity (DWMH) on brain MRI, and shorter telomere length would be predictors of mortality in community-dwelling Japanese elderly. METHODS: We followed 259 individuals (74% of all the residents at age 70) from age 70 to 83 years. The mean observation period was 133 ±â€¯34 months. The key clinical characteristics examined included DWMH on brain MRI and cognitive function. Telomere length was also measured in 81 subjects. Both univariate and multivariate analyses were performed. RESULTS: Of the 259 subjects, 69 subjects (30 men, 39 women; 26.6%) died during the follow-up period. Cognitive impairment, smoking habits, diabetes mellitus, and moderate to severe DWMH were significant predictors of total mortality in univariate analysis. However, only cognitive impairment and moderate to severe DWMH remained as significant independent predictors of death in multivariate analysis. The rate of mortality increased with additional number of risk factors (cognitive impairment and DWMH). The total mortality of subjects with both cognitive impairment and DWMH was 71.4%. The median telomere length was 7.8 kb in the deceased and 8.2 kb in the living subjects. The deceased subjects had significantly shorter telomere length (P = .0025) than the living subjects. Telomere length with moderate to severe DWMH was higher than without moderate to severe DWMH on brain MRI (P = .017). CONCLUSIONS: The present study revealed that cognitive impairment, DWMH, and shorter telomere length were significant predictors of total mortality in the community-dwelling Japanese elderly. Furthermore, the combination of cognitive impairment and DWMH increased the mortality rate, as compared with a single risk factor. It is also clarified that a significant difference was present in telomere length by severity of DWMH.

A Segmental Copy Number Loss of the SFMBT1 Gene Is a Genetic Risk for Shunt-Responsive, Idiopathic Normal Pressure Hydrocephalus (iNPH): A Case-Control Study.

Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82-23.79, p = 1.8 x 10-5) and 6.3% of patients with Parkinson's disease (n = 32) (OR = 5.18, 95%CI: 1.1-50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.

Inflammatory Pseudotumor of the Brain Parenchyma with IgG4 Hypergammaglobulinemia.

A 58-year-old woman with a 1-month history of right hand clumsiness and speaking difficulty was admitted to our hospital. A neurological examination revealed sensory aphasia and right hemiparesis. Her laboratory tests showed elevated serum levels of IgG and IgG4, pancytopenia, and liver dysfunction. The results of the imaging studies of her abdomen were compatible with sclerosing cholangitis. Brain MRI showed extensive signal abnormalities in the left hemisphere on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, extending from left internal capsule to the cerebral peduncle with an irregularly enhancing lesion in the left parietal lobe. A brain biopsy revealed lymphocyte and plasma cell infiltration and reactive gliosis. Most of the plasma cells were IgG positive; however, IgG4-positive plasma cells were sparsely observed. After the initiation of betamethasone treatment, her symptoms and the brain MRI abnormalities showed significant improvement. The brain biopsy results did not meet the current criteria of IgG4-related disease. This is the first reported case of a tumefactive lesion of the brain parenchyma with serum IgG4 elevation, which was responsive to steroid treatment. The accumulation of a greater number of reports on the pathological investigation of cases of possible IgG4-related disease may help to elucidate the exact role of IgG4 in IgG4-related disorders.

[Binocular diplopia and ptosis due to snakebite (Agkistrodon blomhoffi "mamushi")--a case report].

We treated a patient who developed binocular diplopia and ptosis after being bitten by an Agkistrodon blomhoffi (mamushi). The patient was a 49-year-old man who presented with binocular diplopia after the snakebite on the second finger of his right hand. He experienced local pain and swelling and a few hours later, he developed diplopia. In the primary position he had no tropia. On the basis the ocular angle of deviation measured by a Hess chart test, he was diagnosed with paresis of the medial rectus muscle paresis. Binocular diplopia persisted for 2 weeks. The venom of A. blomhoffi venom mainly consists of hemolytic toxins, but it also contains 2 types of neurotoxins--an alpha-toxin and a beta-toxin. Neurotoxins affects the neuromuscular junction (NMJ). The alpha-toxin acts postsynaptic inhibition as a competitive inhibitor of acetylcholine and causes postsynaptic inhibition; these effects are similar to those of the anti-acetylcholine receptor antibody identified in patients with myasthenia gravis. The beta-toxin inhibits acetylcholine release by disrupting the presynaptic membrane, and thus, its effects cannot be blocked by the anticholinesterase edrophonium chloride. Although both antiserum and cepharanthine are widely used for the treatment of snakebites, there is no evidence of a specific effective therapy for the eye manifestation after snakebite. However, it these manifestation improves in about 2 weeks without any specific treatment. Our case suggested that the occurrence of subjective binocular diplopia without objective tropia could be caused by snakebite.