The Movement Disorder Society Criteria: Its Clinical Usefulness in Multiple System Atrophy.

Objective In 2022, Wenning et al. proposed the Movement Disorder Society Criteria (MDS Criteria) for the Diagnosis of Multiple System Atrophy (MSA). These criteria were expected to provide useful alternatives to the second consensus statement. We examined trends in these diagnostic criteria. Methods We used patient data registered with the Hokkaido Rare Disease Consortium for Multiple System Atrophy, which has been recruiting patients with MSA through medical facilities in Hokkaido since November 2014. Patients were evaluated according to the MDS criteria based on neurological examinations and imaging findings at three separate times: the first evaluation, the time of enrollment (diagnosis), and the most recent evaluation (final evaluation). Results The MDS criteria were examined in 68 of 244 patients enrolled between November 2014 and July 2022. At the initial evaluation, the classifications were as follows: clinically established (n=27; 39.7%); clinically probable (n=13; 19.1%); possible prodromal (n=12; 17.6%); and negative (did not meet criteria (n=16; 23.5%). At the time of diagnosis, the classifications were as follows: clinically established (n=45; 66.2%); clinically probable (n=12; 17.6%); possible prodromal (n=4; 5.9%); and negative (n=7; 10.3%). At the final evaluation, the classifications were as follows: clinically established (n=52; 76.5%); clinically probable (n=9; 13.2%); possible prodromal (n=2; 2.9%); and negative (n=5; 7.4%). Conclusions We were able to clarify the changes in the criteria values and transition of patients due to the clarification of imaging and supportive findings in the MDS criteria.

An autopsy case report of adult-onset Krabbe disease: Comparison with an infantile-onset case.

Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Klüver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain.

Voxel-based analysis of age and gender effects on striatal [123I] FP-CIT binding in healthy Japanese adults.

OBJECTIVE: Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a conventional regions of interest-based analysis. Here, we investigated age and gender effects on striatal DaT binding at the voxel level, using a multicenter database of [(123)I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([(123)I] FP-CIT)-single photon emission computed tomography (SPECT) scans in 256 healthy Japanese adults. METHODS: We used the Southampton method to calculate the specific binding ratios (SBRs) of each subject's striatum and then converted the [123I] FP-CIT SPECT images to quantitative SBRs images. To investigate the effects of age and gender effects on striatal DaT binding, we performed a voxel-based analysis using statistical parametric mapping. Gender differences were also compared between young to middle-aged subjects and elderly subjects (age threshold: 60 years). RESULTS: When all subjects were explored as a group, DaT binding throughout the striatum decreased with advancing age. Among all subjects, the females showed higher DaT binding in the bilateral caudate compared to the males. In the young to middle-aged subjects, the females showed higher DaT binding throughout the striatum (with a slight caudate predominance) versus the males. In the elderly, there were no gender differences in striatal DaT binding. CONCLUSION: Our findings of striatal subregional age- and gender-related differences may provide useful information to construct a more detailed DaT database in healthy Japanese subjects.

Intravenous fosphenytoin therapy for rescue of acute trigeminal neuralgia crisis in patients awaiting neurosurgical procedures: A cross-sectional study.

Few treatments exist for acute attacks of trigeminal neuralgia. Therefore, this study aimed to investigate the efficacy and safety of an intravenous fosphenytoin therapy protocol in a trigeminal neuralgia crisis. We conducted a single-center, retrospective, observational study of the records of 20 patients with trigeminal neuralgia who received intravenous fosphenytoin therapy (15 mg/mL in normal saline at 50 mg/min for 15 min, total 750 mg) during hospitalization between September 2015 and August 2020. Serum phenytoin concentration was measured 30 min post-infusion. Pain severity was evaluated using a numerical rating scale and was analyzed for statistical significance. The mean age of the patients was 67.5 years (female, 50.0%). The median numerical rating scale score (interquartile range) of pain severity was 2.35 (0-10), 0.65 (0-5), 0.15 (0-1), 2.00 (0-8), and 4.30 (0-10) at 15, 30, and 60 min, and 12 and 24 h, respectively (p < .001); the numerical rating scale score was 10 before treatment. Reduction in pain 24 h following treatment was significant. The mean phenytoin concentration was 12.8 µg/mL 30 min post-treatment. While mild dizziness occurred in four patients, all could walk independently within 60 min. The mean age and weight of patients with mild dizziness were significantly higher and lower, respectively (p < .001), than those of other patients. These results may provide physicians with new insights into the innovative therapeutic option of intravenous fosphenytoin and contribute to advancements in treating acute trigeminal neuralgia crisis.

Multiple system atrophy in Hokkaido, Japan: a prospective registry study of natural history and symptom assessment scales followed for 5 years.

OBJECTIVES: Multiple system atrophy (MSA) is a refractory neurodegenerative disease, but novel treatments are anticipated. An accurate natural history of MSA is important for clinical trials, but is insufficient. This regional registry was launched to complement clinical information on MSA. SETTING: Patient recruitment started in November 2014 and is ongoing at the time of submission. The number of participating facilities was 66. Postal surveys were sent to medical facilities and patients with MSA in Hokkaido, Japan. PARTICIPANTS: After obtaining written consent from 196 participants, 184 overview surveys and 115 detailed surveys were conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: An overview survey evaluated conformity to diagnostic criteria and a detailed survey implemented an annual assessment based on the Unified Multiple System Atrophy Rating Scale (UMSARS). RESULTS: At the time of registration, 58.2% of patients were diagnosed with cerebellar symptoms predominant type MSA (MSA-C) and 29.9% were diagnosed with parkinsonism predominant type MSA (MSA-P). UMSARS Part Ⅳ score of 4 or 5 accounted for 53.8% of participants. The higher the UMSARS Part Ⅳ score, the higher the proportion of MSA-P. At baseline, levodopa was used by 69 patients (37.5%) and the average levodopa dose was 406.7 mg/day. The frequency of levodopa use increased over time. Eleven cases changed from MSA-C to MSA-P during the study, but the opposite was not observed. Information about survival and causes of death was collected on 54 cases. Half of deaths were respiratory-related. Sudden death was recorded even in the group with UMSARS Part Ⅳ score of 1. CONCLUSIONS: This study is the first large-scale prospective MSA cohort study in Asia. MSA-C was dominant, but the use of antiparkinsonian drugs increased over the study period. Changes from MSA-C to MSA-P occurred, but not vice versa.

Japanese multicenter database of healthy controls for [123I]FP-CIT SPECT.

PURPOSE: The aim of this multicenter trial was to generate a [123I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. METHODS: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30-83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. RESULTS: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30-39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70-79 age group. CONCLUSIONS: This study provided a large-scale quantitative database of [123I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database.

[A case of cerebral syphilitic gumma mimicking a brain tumor].

We report a case of young immunocompetent woman who was presented with a left parieto-temporal mass as the first and single manifestation of syphilis. A 23 year-old woman with no significant past medical history was reffered to our hospital due to 3 month history of headache. She had a single unprotected sexual intercourse with a promiscuous man 6 month before the time of admission. Physical and neurological examinations revealed no obvious abnormalities. A brain tumor was firstly suggested according to the findings of brain magnetic resonance imaging (MRI). However, the serologic and cerebrospinal fluid test of syphilis proved to be positive, syphilitic gumma was most likely suspected. She responded dramatically to benzylpenicillin potassium. Cerebral syphilitic gumma is a rare manifestations of the neurosyphilis. Treponemal invasion of the cerebrospinal fluid occurs in approximately 25 to 60% of patients after the infection, but most cases spend asymptomatic. Cerebral gumma should be considered in differential diagnosis of any intracranial mass lesions, even in the early syphilitic stages.

[Efficacy of intravenous phenobarbital treatment for status epilepticus].

PURPOSE: Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. METHODS: Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. RESULTS: The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. CONCLUSION: IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

Clinicopathological features of neuropathy associated with lymphoma.

Lymphoma causes various neurological manifestations that might affect any part of the nervous system and occur at any stage of the disease. The peripheral nervous system is one of the major constituents of the neurological involvement of lymphoma. In this study we characterized the clinical, electrophysiological and histopathological features of 32 patients with neuropathy associated with non-Hodgkin's lymphoma that were unrelated to complications resulting from treatment for lymphoma. Nine patients had pathologically-proven neurolymphomatosis with direct invasion of lymphoma cells into the peripheral nervous system. These patients showed lymphomatous cell invasion that was more prominent in the proximal portions of the nerve trunk and that induced demyelination without macrophage invasion and subsequent axonal degeneration in the portion distal from the demyelination site. Six other patients were also considered to have neurolymphomatosis because these patients showed positive signals along the peripheral nerve on fluorodeoxyglucose positron emission tomography imaging. Spontaneous pain can significantly disrupt daily activities, as frequently reported in patients diagnosed with neurolymphomatosis. In contrast, five patients were considered to have paraneoplastic neuropathy because primary peripheral nerve lesions were observed without the invasion of lymphomatous cells, with three patients showing features compatible with chronic inflammatory demyelinating polyneuropathy, one patient showing sensory ganglionopathy, and one patient showing vasculitic neuropathy. Of the other 12 patients, 10 presented with multiple mononeuropathies. These patients showed clinical and electrophysiological features similar to those of neurolymphomatosis rather than paraneoplastic neuropathy. Electrophysiological findings suggestive of demyelination were frequently observed, even in patients with neurolymphomatosis. Eleven of the 32 patients, including five patients with neurolymphomatosis, fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic criteria of definite chronic inflammatory demyelinating polyneuropathy. Some of these patients, even those with neurolymphomatosis, responded initially to immunomodulatory treatments, including the administration of intravenous immunoglobulin and steroids. Patients with lymphoma exhibit various neuropathic patterns, but neurolymphomatosis is the major cause of neuropathy. Misdiagnoses of neurolymphomatosis as chronic inflammatory demyelinating polyneuropathy are frequent due to a presence of a demyelinating pattern and the initial response to immunomodulatory treatments. The possibility of the concomitance of lymphoma should be considered in various types of neuropathy, even if the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy are met, particularly in patients complaining of pain.

Correlation between periodic sharp wave complexes and diffusion-weighted magnetic resonance images in early stage of Creutzfeldt-Jakob disease: a report of two cases.

We evaluated the correlation between the periodic sharp wave complexes (PSWC) on EEG and the spreading lesions on diffusion-weighted (DW) magnetic resonance images (MRI) in two cases of Creutzfeldt-Jakob disease (CJD). In Case 1, DW-MRI showed increased signal intensity in bilateral caudate, bilateral parietal, and right temporo-occipital cortex at 7 weeks after onset. EEG showed PSWC of 1Hz frequency at 8 weeks after onset. Source localization analysis of the PSWC was conducted by low resolution electromagnetic tomography (LORETA), and localized the source in the cortex of bilateral parietal lobes and mesial frontal lobe, predominantly on the right side. At 10 weeks after onset, the PSWC source spread to bilateral parietal and frontal lobes, and the same spread was also observed for the lesion depicted on DW-MRI. In Case 2, DW images showed high signal intensity in the right parietal cortical lesion at 4 weeks after onset. PSWC of 2Hz frequency were seen in the routine EEG, and the source was localized in bilateral frontal lobes and right parietal lobe at 7 weeks after onset. The lesions on DW images also spread to bilateral frontal and parietal lobes. Nine weeks after onset, the source of PSWC extended to the right frontal lobe and bilateral parietal lobes, while the lesions on DW images progressed to the right temporal lobe and bilateral fronto-parieto-occipital lobes. Spreading DW-MRI lesions may correlate with the appearance of PSWC.

Dystonic posturing associated with putaminal hyperperfusion depicted on subtraction SPECT.

PURPOSE: Dystonic posturing (DP) is one of the most reliable lateralizing indicators for temporal lobe epilepsy (TLE). We evaluated the ictal hyperperfusional areas in patients with DP by using ictal-interictal subtraction single-photon emission computed tomography (SPECT). METHODS: Ninety-seven patients were treated surgically for intractable TLE, and 39 patients underwent ictal and interictal SPECT studies with the same isotope. These patients were divided into three groups: group I with DP of the contralateral side extended to the epileptogenic focus, group II with elevated muscle tonus but without DP, and group III without DP or alteration of muscle tonus. Ictal, interictal SPECT and thin-slice magnetic resonance imaging (MRI) were overlaid by using the automatic multimodality registration program to construct ictal-interictal subtracted images of SPECT on MRI. RESULTS: Thirteen patients belonged to group I; 14, to group II; and 12, to group III. A statistically significant difference in hyperperfusion rate was observed in the putamen (10 patients in group I, three in group II and two in group III; p < 0.01) and mesial temporal lobe (10 patients in group I, seven in group II, and two in group III; p < 0.05) on the ipsilateral side of the epileptogenic focus. No statistically significant difference was observed for other ictal symptoms except ipsilateral upper-limb automatism (eight patients in group I, three in group II, and none in group III; p < 0.01). CONCLUSIONS: A strong correlation between DP and hyperperfusion in the putamen and mesial temporal lobe was demonstrated. Some patients showed a wide hyperperfusion area extending from the mesial temporal lobe to putamen, which may correspond to the propagation of epileptic discharges. Our results suggest a correlation between hyperperfusion of putamen and contralateral dystonic posturing.

Potato Tuber Necrotic Ringspot Disease Occurring in Japan: Its Association with Potato virus Y Necrotic Strain.

Unfamiliar necrotic symptoms on or within potato tubers of cultivars Nishiyutaka and Dejima were observed in Nagasaki prefecture, Japan, in 1992. Symptoms were typically on the surface of the tuber, which either protruded at first and then became sunken, or showed necrotic spots, with necrosis within the tubers. Symptoms sometimes appeared at harvesting but more often appeared after storage for several months. Investigations revealed that the causal agents of the disease were isolates of Potato virus Y necrotic strain (PVYNTN) and the disease was potato tuber necrotic ringspot disease (PTNRD), previously reported in Europe and Lebanon. Five potato cultivars were inoculated with an isolate from necrotic tubers. The highest percentage of progeny tubers showing PTNRD was found in cv. Nishiyutaka (23.3%). In contrast, cvs. Shima-bara, Mayqueen, and Danshaku showed a low percentage of PTNRD. Additional potato tubers with PTNRD were also observed after storage of the tubers. To investigate the relatedness between isolates of PVYNTN and of necrotic strain PVYN, previously isolated in Japan, Nishiyu-taka was inoculated with an isolate of PVYN, which also induced PTNRD. Nucleotide sequences of coat protein (CP) genes of six PVYNTN isolates were determined. The CPs were 267 amino acids in length, with a substitution of one or no amino acid among each of the six isolates. The phylogenetic relationship based on nucleotide sequences of CP genes showed that these six PVYNTN isolates clustered together with PVYN isolates. This is the first report of PTNRD caused by PVYNTN isolates in Asia.