植田 晃広

BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) is a neurodegenerative disease with characteristic motor and autonomic symptoms. Impaired brain serotonergic innervation can be associated with various clinical indices of MSA; however, the relationship between clinical symptoms and cerebrospinal fluid (CSF) levels of 5-hydroxyindole acetic acid (5-HIAA), a main serotonin metabolite, has not been fully elucidated. METHODS: To compare CSF 5-HIAA levels between patients with MSA and healthy controls, we included 33 controls and 69 MSA patients with either predominant parkinsonian or cerebellar ataxia subtypes. CSF 5-HIAA levels were measured using high-performance liquid chromatography. Additionally, we investigated correlations between CSF 5-HIAA and various clinical indices in 34 MSA patients. RESULTS: CSF 5-HIAA levels were significantly lower in MSA patients than in controls (p < 0.0001). Probable MSA patients had lower CSF 5-HIAA levels than possible MSA patients (p < 0.001). In MSA patients, CSF 5-HIAA levels were inversely correlated with scores in Parts 1, 2, and 4 of the Unified Multiple System Atrophy Rating Scale, and with systolic and diastolic blood pressure in Part 3. Structural equation modeling revealed significant paths between serotonin and clinical symptoms, and significance was highest for activities of daily living, walking, and body sway. CONCLUSIONS: Serotonin dysfunction, as assessed by CSF 5-HIAA levels, may implicate greater MSA severity.

OBJECTIVE: Recent studies have revealed an association between Parkinson's disease (PD) and Fabry disease, a lysosomal storage disorder; however, the underlying mechanisms remain to be elucidated. This study aimed to investigate the enzymatic properties of serum alpha-galactosidase A (GLA) and compared them with the clinical parameters of PD. METHODS: The study participants consisted of 66 sporadic PD patients and 52 controls. We measured serum GLA activity and calculated the apparent Michaelis constant (Km ) and maximal velocity (Vmax ) by Lineweaver-Burk plot analysis. Serum GLA protein concentration was measured by enzyme-linked immunosorbent assay. We examined the potential correlations between serum GLA activity and GLA protein concentration and clinical features and the plasma neurofilament light chain (NfL) level. RESULTS: Compared to controls, PD patients showed significantly lower serum GLA activity (P < 0.0001) and apparent Vmax (P = 0.0131), but no change in the apparent Km value. Serum GLA protein concentration was lower in the PD group (P = 0.0168) and was positively associated with GLA activity. Serum GLA activity and GLA protein concentration in the PD group showed a negative correlation with age. Additionally, serum GLA activity was negatively correlated with the motor severity score and the level of plasma NfL, and was positively correlated with the score of frontal assessment battery. INTERPRETATION: This study highlights that the lower serum GLA activity in PD is the result of a quantitative decrement of GLA protein in the serum and that it may serve as a biomarker of disease severity.

BACKGROUND: Parkinson's disease (PD) is associated with cognitive decline through multiple mechanisms, including Alzheimer's disease (AD) pathology and cortical Lewy body involvement. However, its underlying mechanisms remain unclear. Recently, AD-related plasma biomarkers have emerged as potential tools for predicting abnormal pathological protein accumulation. We aimed to investigate the association between AD-related plasma biomarkers and cognitive decline in PD patients. METHODS: Plasma biomarkers were measured in 70 PD patients (49 with nondemented Parkinson's disease (PDND) and 21 with Parkinson's disease dementia (PDD)) and 38 healthy controls (HCs) using a single-molecule array. The study evaluated (1) the correlation between plasma biomarkers and clinical parameters, (2) receiver operating characteristic curves and areas under the curve to evaluate the discrimination capacity of plasma biomarkers among groups, and (3) a generalized linear model to analyze associations with Addenbrooke's Cognitive Examination-Revised and Montreal Cognitive Assessment-Japanese version scores. RESULTS: Plasma glial fibrillary acidic protein significantly correlated with cognitive function tests, including all subdomains, with a notable increase in the PDD group compared with the HC and PDND groups, while plasma neurofilament light chain captured both cognitive decline and disease severity in the PDND and PDD groups. Plasma beta-amyloid 42/40 and pholphorylated-tau181 indicated AD pathology in the PDD group, but plasma beta-amyloid 42/40 was increased in the PDND group compared with HCs and decreased in the PDD group compared with the PDND group. CONCLUSIONS: AD-related plasma biomarkers may predict cognitive decline in PD and uncover underlying mechanisms suggesting astrocytic pathologies related to cognitive decline in PD.

Accumulating evidence suggests that various sphingolipids and glycosphingolipids can act as mediators for inflammation or signaling molecules in the nervous system. In this article, we explore the molecular basis of a new neuroinflammatory disorder called encephalomyeloradiculoneuropathy (EMRN), which affects the brain, spinal cord, and peripheral nerves; in particular, we discuss whether glycolipid and sphingolipid dysmetabolism is present in patients with this disorder. This review will focus on the pathognomonic significance of sphingolipid and glycolipid dysmetabolism for the development of EMRN and the possible involvement of inflammation in the nervous system.

OBJECTIVE: In this study, we aimed to clarify the relationship between initial treatment response, prednisolone (PSL) dosage, clinical type, and recurrence in patients with hypertrophic pachymeningitis (HP). METHODS: The study cohort comprised eight patients with HP who had been admitted to our hospital from April 2015 to June 2020. Diagnostic criteria for HP included neurological abnormalities and dural thickening on magnetic resonance gadolinium-enhanced T1-weighted images. RESULTS: Relevant characteristics of the eight study patients are as follows. There were two men and six women. The average age at onset was 58.3 (range: 29-79) years. Three of them had myeloperoxidase-antineutrophil cytoplasmic antibody-related vasculitis, one immunoglobulin G4-related disease, and one ulcerative colitis. The remaining three patients had idiopathic HP. The average maximum dosage of PSL was 0.79 mg/kg/day, and the average daily maintenance dosage 0.18 mg/kg/day. Three patients needed additional immunosuppressive drugs. Both idiopathic and secondary HP initially responded well to PSL, with improvement in activities of daily living. Six patients had some sequelae related to cranial nerve involvement. No relapses occurred while the patients were taking moderate doses of PSL; however, all patients with idiopathic HP had recurrences when their PSL dosage was reduced. CONCLUSIONS: Patients with idiopathic HP and HP associated with immune disorders respond to steroids and immunosuppressive drugs and recover well. However, there is a high rate of relapse after reduction of PSL dosage, mainly in those with idiopathic HP.

BACKGROUND: No studies have examined the associations between adult height and ischemic stroke subtypes. METHODS: We conducted a population-based case-control study that included 2,451 thrombotic and 687 embolic stroke cases, as well as 1,623 intracerebral and 768 subarachnoid hemorrhage cases without history of stroke aged 40-79 years, and the same number of sex- and age-matched controls. Cases and controls were grouped according to the quintile cut-off values of height in controls, and the third quintile, which was approximately the average height group, was used as the reference group. Height was also examined as a continuous variable as divided by one standard deviation of height in controls. The analyses were carried out separately for participants aged 40-59 years and 60-79 years. RESULTS: In both younger and older men, continuous height was linearly inversely associated with total and thrombotic strokes, and the shortest quintile compared to the reference was associated with increased risks of these strokes. Although height was linearly inversely associated with embolic stroke and intracerebral hemorrhage in younger men, the shortest quintile did not show increased risks of these strokes. Height did not seem to be associated with total stroke and any stroke subtypes in younger women. In contrast, the tallest quintile was significantly associated with increased risks of total stroke and intracerebral hemorrhage, and height tended to be positively associated with these strokes in older women. CONCLUSIONS: We reported the associations between adult height and ischemic stroke subtypes for the first time, which differed according to sex and age-group.

This review summarizes improvements in understanding the pathophysiology and early clinical symptoms of multiple system atrophy (MSA) and advancements in diagnostic methods and disease-modifying therapies for the condition. In 2022, the Movement Disorder Society proposed new diagnostic criteria to develop disease-modifying therapies and promote clinical trials of MSA since the second consensus was proposed in 2008. Regarding pathogenesis, cutting-edge findings have accumulated on the interactions of α-synuclein, neuroinflammation, and oligodendroglia with neurons. In neuroimaging, introducing artificial intelligence, machine learning, and deep learning has notably improved diagnostic accuracy and individual analyses. Advancements in treatment have also been achieved, including immunotherapy therapy against α-synuclein and serotonin-targeted and mesenchymal stem cell therapies, which are thought to affect several aspects of the disease, including neuroinflammation. The accelerated progress in clarifying the pathogenesis of MSA over the past few years and the development of diagnostic techniques for detecting early-stage MSA are expected to facilitate the development of disease-modifying therapies for one of the most intractable neurodegenerative diseases.

Glycolipids are now known to be rapidly converted to mediators for inflammatory reactions or to signaling molecules that control inflammatory events in the nervous system. The present study aimed to explore whether disturbed glycolipids metabolism in the nervous system is present in patients with a neuroinflammatory disorder, encephalo-myelo-radiculo-neuropathy (EMRN), because most EMRN patients have been reported to exhibit autoantibodies against neutral glycolipids. Although molecular pathogenesis of this disorder remains unknown, we tried to search the immunochemical abnormalities in this disorder. ELISA for activated peripheral C5 complement and mass spectrometry analysis of cerebrospinal fluid clearly disclosed a significant upregulation of active C5 complement, C5a levels in sera as well as a significant accumulation of species-specific ceramides but not sphingomyelin in cerebrospinal fluid from EMRN patients. Furthermore, we confirmed the occurrence of anti-neutral glycolipids antibodies in all EMRN patients. Thus, the present study might indicate the pathophysiology of this disorder is the dysregulation of glycolipids metabolism and abnormal production of autoantibodies against neutral glycolipids resulting in the abnormal complement activation, although molecular basis for these sphingolipids dysregulation and the occurrence of autoantibodies against glycolipids remains to be elucidated at present. The present study implicates a new therapeutic strategy employing anti-ceramide and/or anti-complement therapy for this disorder.

The full spectrum of human herpesviruses (HHV)-associated neuroinfectious diseases in immunocompetent adults remains unclear. Hence, we sought to elucidate the epidemiology and clinical features of these diseases. The study subjects were patients over 16 years old suspected of neuroinfectious diseases who underwent spinal tap performed by neurologists in our university hospital between April 2013 and March 2018. The presence of seven HHV DNAs in cerebrospinal fluid (CSF) was determined by real-time PCR. HHV DNAs were detected in 33 (10.2%) of the 322 patients. The most frequently detected herpesvirus was varicella zoster virus (VZV) (19 patients), followed by HHV-6 (four patients), herpes simplex virus (HSV)-1 (three patients), HSV-2 (three patients), and Epstein-Barr virus (two patients). HHV DNAs were detected in CSF collected from patients with various neuroinfectious diseases, including myelitis, peripheral neuritis, encephalitis, and meningitis. All patients with HSV-1 DNA had encephalitis, whereas all patients with HSV-2 DNA had meningitis. Eleven of the 19 patients with VZV DNA had meningitis. Patients with VZV-associated encephalitis (median age, 80 years) were significantly older than non-encephalitis patients (median age, 60.5 years) (P = 0.046). Although post-herpetic neuralgia was observed in seven (54%) of the 13 patients with VZV and without encephalitis, no such neurological sequela was observed in the four encephalitis patients. In conclusion, HHVs were associated with approximately 10% of neuroinfectious diseases in this cohort. VZV was the most common pathogen, probably due to the large number of VZV meningitis patients. In addition, patients with VZV-associated meningitis were significantly younger than patients with VZV-associated encephalitis.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder. We report a 59-year-old man who presented with progressive encephalomyelitis causing diplopia, bulbar palsy, severe dysautonomia, followed by stiffness and myoclonic cluster. Laboratory tests showed mild pleocytosis, with markedly elevated plasma levels of norepinephrine, epinephrine, and arginine vasopressin. Glycine-receptor antibodies were identified in both serum and CSF. Despite a poor response to methylprednisolone, immunoglobulins, and plasma exchange, α-blocker stabilized dysautonomia. Dysautonomia is presumed to be due to antibody-mediated disinhibited sympathetic hyperactivity; however, this case suggests that concomitant use of α-blocker with immunotherapy may ameliorate dysautonomia.

Nemaline myopathy (NM) is a rare muscle disease with various clinical types. In some cases, NM can lead to type 2 respiratory failure and right heart failure. We herein report a patient with congenital NM with nebulin gene mutation who presented with acute right heart failure and type 2 respiratory failure due to respiratory muscle paralysis after upper respiratory tract infection, needing a permanent ventilator for assistance. However, the limb and trunk muscle strengths were within normal limits. This case showed that NM should be considered as a cause of right heart failure and type 2 respiratory failure.

To understand the mechanisms underlying preserved and impaired cognitive function in healthy aging and dementia, respectively, the spatial relationships of brain networks and mechanisms of their resilience should be understood. The hub regions of the brain, such as the multisensory integration and default mode networks, are critical for within- and between-network communication, remain well-preserved during aging, and play an essential role in compensatory processes. On the other hand, these brain hubs are the preferred sites for lesions in neurodegenerative dementias, such as Alzheimer's disease. Disrupted primary information processing networks, such as the auditory, visual, and sensorimotor networks, may lead to overactivity of the multisensory integration networks and accumulation of pathological proteins that cause dementia. At the cellular level, the brain hub regions contain many synapses and require a large amount of energy. These regions are rich in ATP-related gene expression and had high glucose metabolism as demonstrated on positron emission tomography (PET). Importantly, the number and function of mitochondria, which are the center of ATP production, decline by about 8% every 10 years. Dementia patients often have dysfunction of the ubiquitin-proteasome and autophagy-lysosome systems, which require large amounts of ATP. If there is low energy supply but the demand is high, the risk of disease can be high. Imbalance between energy supply and demand may cause accumulation of pathological proteins and play an important role in the development of dementia. This energy imbalance may explain why brain hub regions are vulnerable to damage in different dementias. Here, we review (1) the characteristics of gray matter network, white matter network, and resting state functional network changes related to resilience in healthy aging, (2) the mode of resting state functional network disruption in neurodegenerative dementia, and (3) the cellular mechanisms associated with the disruption.

The pathophysiology of neuralgic amyotrophy (NA) remains to be elucidated. However, high-resolution magnetic resonance imaging and ultrasound sonography have provided new insights into the mechanism underlying the development of NA and its diagnosis. We report a case of idiopathic distal NA with hyperintensity and thickening in the inferior trunk extending to the posterior and medial fasciculus of the left brachial plexus, which was detected by magnetic resonance neurography (MRN) with diffusion-weighted whole-body imaging with background body signal suppression (DWIBS). The abnormal signal intensity diminished after the improvement of symptoms following corticosteroid treatment. MRN with DWI can help diagnose distal NA and evaluate the post-therapeutic response.

The present report documents a patient harboring an alpha-synuclein p.A53T variant from a family presenting with autosomal dominant inheritance, including four patients clinically diagnosed with Parkinson's disease (PD) and two with dementia. The alpha-synuclein p.A53T variant is linked to young- or middle-aged onset parkinsonism and cognitive decline. Our patient had a different haplotype from that of a patient with a p.A53T variant from an Italian family. The proband presented at 42 years of age with progressive parkinsonism and good response to levodopa in the early stages of the disease. At 46 years of age, he developed delusions and cognitive decline. Brain magnetic resonance imaging showed bilateral atrophic changes in the hippocampus and temporal lobes. He died of pneumonia at the age of 52 years. Neuropathological examination revealed severe neuronal loss in the substantia nigra, locus coeruleus, and dorsal nucleus of the vagus nerve, as well as widespread Lewy pathology including Lewy bodies and neurites, corresponding to Braak stage 6, and diffuse neocortical-type PD. There was mild appearance of tau pathology and glial cytoplasmic inclusion, in the absence of TDP-43 pathology. Alpha-synuclein p.A53T characteristically cause the Lewy body pathology and the symptoms, that resembled those of the reported patients with p.A53T.

＜文献概要＞孤発性小脳性運動失調症の代表的疾患は小脳性運動失調優位型多系統萎縮症(MSA-C)と皮質性小脳萎縮症である。両疾患は,αシヌクレイン病理により明瞭に異なる。しかし,MSA-Cは発症から小脳性運動失調と自律神経不全が揃うのに約2年かかり,小脳失調のみを呈する時期(mono system atrophy)は10年以上に及び得る。Mono system atrophyの理解は,早期診断と創薬開発に重要である。

ヒトの脳脊髄液中には糖脂質が存在する。今回私たちは、ヒト脳脊髄液中に含まれる糖脂質を高感度で分析することを目的とし、高速クロマトグラフィー/タンデム質量分析法を用いた脂質分析系を構築した。構築した分析系を用いてヒト脳脊髄液由来脂質抽出物を分析したところ、意外にもCeramide dihexoside(二糖を有するセラミド)であると考えられるピークが2つ検出された。同様の2つのピークはHeLa細胞由来脂質抽出物においても検出された。グルコシルセラミド(GlcCer)、ガラクトシルセラミド(GalCer)、ガラビオシルセラミド(Gb2)を合成するそれぞれの酵素の遺伝子をノックアウトしたHeLa細胞を用いた脂質分析結果より、片方のピークはGlcCer合成酵素欠損で発現が低下し、もう片方のピークはGalCer合成酵素欠損またはGb2合成酵素欠損で発現が低下した。また、ヒト脳脊髄液よりCeramide dihexosideを含む画分を精製したところ、精製画分はGb2が有する糖鎖構造を認識する志賀トキシン陽性であることがわかった。これらの結果より、ヒト脳脊髄液ならびにHeLa細胞で検出されたCeramide dihexosideはラクトシルセラミドとGb2である可能性が示唆された。これまでGb2がヒト脳脊髄液中に存在することは報告されておらず、今回初めてその存在が明らかになった。(著者抄録)

ヒトの脳脊髄液中には糖脂質が存在する。今回私たちは、ヒト脳脊髄液中に含まれる糖脂質を高感度で分析することを目的とし、高速クロマトグラフィー/タンデム質量分析法を用いた脂質分析系を構築した。構築した分析系を用いてヒト脳脊髄液由来脂質抽出物を分析したところ、意外にもCeramide dihexoside(二糖を有するセラミド)であると考えられるピークが2つ検出された。同様の2つのピークはHeLa細胞由来脂質抽出物においても検出された。グルコシルセラミド(GlcCer)、ガラクトシルセラミド(GalCer)、ガラビオシルセラミド(Gb2)を合成するそれぞれの酵素の遺伝子をノックアウトしたHeLa細胞を用いた脂質分析結果より、片方のピークはGlcCer合成酵素欠損で発現が低下し、もう片方のピークはGalCer合成酵素欠損またはGb2合成酵素欠損で発現が低下した。また、ヒト脳脊髄液よりCeramide dihexosideを含む画分を精製したところ、精製画分はGb2が有する糖鎖構造を認識する志賀トキシン陽性であることがわかった。これらの結果より、ヒト脳脊髄液ならびにHeLa細胞で検出されたCeramide dihexosideはラクトシルセラミドとGb2である可能性が示唆された。これまでGb2がヒト脳脊髄液中に存在することは報告されておらず、今回初めてその存在が明らかになった。(著者抄録)

Idiopathic basal ganglia calcification (IBGC) is a rare intractable disease characterized by abnormal mineral deposits, including mostly calcium in the basal ganglia, thalamus, and cerebellum. SLC20A2 is encoding the phosphate transporter PiT-2 and was identified in 2012 as the causative gene of familial IBGC. In this study, we investigated functionally two novel SLC20A2 variants (c.680C >T, c.1487G > A) and two SLC20A2 variants (c.82G >A, c.358G >C) previously reported from patients with IBGC. We evaluated the function of variant PiT-2 using stable cell lines. While inorganic phosphate (Pi) transport activity was abolished in the cells with c.82G > A, c.358G >C, and c.1487G >A variants, activity was maintained at 27.8% of the reference level in cells with the c.680C >T variant. Surprisingly, the c.680C >T variant had been discovered by chance in healthy members of an IBGC family, suggesting that partial preservation of Pi transport activity may avoid the onset of IBGC. In addition, we confirmed that PiT-2 variants could be translocated into the cell membrane to the same extent as PiT-2 wild type. In conclusion, we investigated the PiT-2 dysfunction of four SLC20A2 variants and suggested that a partial reduced Pi transport function of PiT-2 might not be sufficient to induce brain calcification of IBGC.

Introduction: Recent studies have indicated that lysosomal dysfunction contributes to the development of idiopathic Parkinson's disease (PD). It is uncertain whether dysregulation of serum lysosomal acid hydrolase activity exists in sporadic PD patients compared with normal controls (NCs) and parkinsonian syndrome (PS) patients.Methods: Sporadic PD patients without GBA1 mutations (n = 68) were matched with normal controls (n = 45), and parkinsonian syndrome patients (n = 32) in terms of family history, age, and sex. We measured the activities of lysosomal enzymes, alpha-galactosidase, beta-galactosidase, and beta-hexosaminidase and examined the possible correlations between lysosomal acid hydrolase activities with age in NCs, PD, and PS patients.Results: beta-Galactosidase activity was significantly higher in the PD and PS than in the NC group (P < 0.001). The beta-galactosidase to alpha-galactosidase and beta-hexosaminidase to beta-galactosidase activity ratios were more useful for distinguishing PD and PS patients from NCs (P < 0.0001). Furthermore, alpha-galactosidase activity was significantly higher in PS patients than both PD and NC groups (p = 0.04). beta-Galactosidase and alpha-galactosidase activities exhibited a statistically significant negative correlation with age in NCs, and beta-hexosaminidase activity showed a positive correlation with age in PS. However, PD patients did not show any of these correlations.Conclusion: Our results suggest the presence of an unknown regulatory mechanism(s) of serum acid hydrolase activities with aging in the normal population and abnormalities in their regulation in PD and PS patients. However, the pattern of dysregulation in these two groups is different. Thus, serum lysosomal acid hydrolase activity can be used as a peripheral biomarker for PD.

Myalgia is sometimes observed in patients with thiamine-deficiency neuropathy. However, the detailed mechanism(s) underlying muscular manifestations have been poorly elucidated. We herein report a possible patient with thiamine-deficiency neuropathy exhibiting muscle weakness and myalgia in lower limbs. The patient exhibited abnormal muscle signal intensities on MRI corresponding to the site of myalgia. After thiamine replacement therapy, rapid improvement of clinical symptoms and abnormal MRI findings were observed. Muscle MRI findings in this case implicated the possible mechanism of myalgia observed in patients with thiamine deficiency neuropathy.

Background: The development of acute multiple embolic infarctions (AMEI) resulting from cancer is known as Trousseau's syndrome (TS). At present, however, there is no good marker for predicting the prognosis of TS patients. In the present study, we evaluated the use of serial D-dimer levels as a prognostic marker for TS.Methods: This retrospective cohort study included 1,409 consecutive acute ischemic stroke patients. We selected a group of patients with TS showing AMEI (n = 38; TS group) and a group of patients with atrial fibrillation (Af) and AMEI (n = 35; Af group) as controls. Serial D-dimer levels were measured between days 7 and 28 after stroke (sub-acute phase) in 21 patients of the TS group and 24 patients of the Af group.Results: D-dimer levels at onset (acute phase) were significantly higher in the TS group (8.45 +/- 1.79 mu g/mL, n = 38) compared with the Af group (1.14 +/- 0.14 mu g/mL, n = 35) (p < 0.0001). In patients for whom serial D-dimer measurements were made, D-dimer levels measured at the sub-acute phase decreased to 0.48 +/- 0.12 mu g/mL (n = 24) in the Af group, but remained elevated in the TS group during the sub-acute phase (11.20 +/- 2.77 mu g/mL, n = 21) (p < 0.0001). In all TS patients in whom serial D-dimer measurements were made, D-dimer levels in 17 patients who died within 500 days (13.31 +/- 3.23 mu g/mL) were significantly higher than those of the four surviving patients (2.23 +/- 0.38 mu g/mL) (cut-off D-dimer level = 3.0 mu g/mL) during this period. Moreover, serial D-dimer levels of 10 patients who died within 90 days (17.78 +/- 4.60 mu g/mL) were significantly higher than those of the 11 patients who survived up to 90 days (5.21 +/- 2.12 mu g/mL) (p < 0.05).Conclusions: Serial D-dimer levels may be a good biomarker for TS as well as a useful predictor of the prognosis of TS patients.

Previous studies have shown that patients with GuiIlain-Barre syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated.nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells.We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity. The data we present here strongly suggest that anti-GM1 caused a significant change in sphingomyelin content of the membrane fraction in PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase activities remained unchanged.Our results indicate, for the first time, that anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell membranes.

Background: Although single-photon emission computerized tomography of the dopamine transporter (DATSPECT) is useful for diagnosing parkinsonian syndrome, its applicability toward the early phase of Parkinson's disease remains unknown. Methods: We enrolled 32 patients showing parkinsonism with normal cardiac I-123-metaiodobenzylguanidine (MIBG) uptake and abnormal DAT-SPECT findings among 84 consecutive patients with parkinsonism. We divided these patients into two groups (group 1: Parkinson's disease, group 2: corticobasal degeneration, progressive supranuclear palsy, multiple system atrophy), and compared their clinical characteristics, specific binding ratios, and striatal asymmetry indexes on DAT-SPECT examinations. Results: The striatal asymmetry indexes were significantly lower in group 1 than in group 2 (p &lt; 0.05), but there were no differences in the specific binding ratios between the two groups. Conclusion: The combined use of striatal asymmetry index on DAT-SPEC' and cardiac MIBG scintigraphy might offer useful clues for the differential diagnosis of the early phase Parkinson's disease from other parkinsonian syndromes. (C) 2017 Elsevier B.V. All rights reserved.

Introduction: To visualize peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), we used MR imaging. We also quantified the volumes of the brachial and lumbar plexus and their nerve roots. Methods: Thirteen patients with CIDP and 12 healthy volunteers were enrolled. Whole- body MR neurography based on diffusionweighted whole- body imaging with background body signal suppression ( DWIBS) was performed. Peripheral nerve volumes were calculated from serial axial MR images. Results: The peripheral nervous system was visualized with 3-dimensional reconstruction. Volumes ranged from 8.7 to 49.5 cm(3)/m(2) in the brachial plexus and nerve roots and from 10.2 to 53.5 cm(3)/m(2) in the lumbar plexus and nerve roots. Patients with CIDP had significantly larger volumes than controls ( P &lt; 0.05), and volume was positively correlated with disease duration. Conclusions: MR neurography and the measurement of peripheral nerve volume are useful for diagnosing and assessing CIDP.

Objective: Acute multifocal embolic infarction (AMEI) is conventionally caused by etiologies such as cardioembolism due to atrial fibrillation (AO, but can also be caused by serious underlying diseases such as cancer. We characterized cancer-related AMEI and identified useful indicators for cancer-associated strokes. Methods: A retrospective analysis was performed on 35 patients with Af-related AMEI and 35 patients with cancer -related AMEI selected from 1235 consecutive patients with acute infarcts. All patients received diffusion weighted magnetic resonance (MR) imaging. Cerebral MR angiography, carotid and cardiac ultrasonography, electrocardiogram-monitoring and whole body computed tomography were also performed on these patients. D-dimer levels were evaluated on admission, and were measured during the sub-acute phase in 19 of the patients with Af and 27 of the patients with cancer. Results: Acute phase D-dimer levels were significantly higher in patients with cancer than in patients with Af alone. The cut-off D-dimer value to identify cancer-associated infarcts was 2.0 mu g/mL. D-dimer levels during the sub-acute phase remained elevated in the cancer patients. Conclusions: We may differentiate cancer-associated AMEI from Af using a D-dimer level &gt;= 2.0 mu g/mL, which does not decrease during the sub-acute phase. (C) 2016 Elsevier B.V. All rights reserved.

We report the case of a 66 year-old woman with chronic atrial fibrillation, hypertrophic cardiomyopathy (HCM), and spinocerebellar atrophy (SCA). Her mother and first-born son had died of heart disease at the ages of 65 and 16 years, respectively. Four of her 8 siblings had died suddenly of unknown cause or of heart disease, and 2 others of cerebral infarction by the 7th decade. Genetic testing revealed that she had a novel mutation (c. 482C &gt; A, p. Alal6lAsp) in the troponin I gene (TNNI3), and no abnormality of the GAA repeat in the frataxin gene. Her older brother with SCA but without HCM was also analyzed, with no abnormality noted in either gene. The Ala161Asp mutation in TNNB was implicated in the pathogenesis of her HCM, though an association between HCM and SCA was not revealed.