Gait video-based prediction of unified Parkinson's disease rating scale score: a retrospective study.

BACKGROUND: The diagnosis of Parkinson's disease (PD) and evaluation of its symptoms require in-person clinical examination. Remote evaluation of PD symptoms is desirable, especially during a pandemic such as the coronavirus disease 2019 pandemic. One potential method to remotely evaluate PD motor impairments is video-based analysis. In this study, we aimed to assess the feasibility of predicting the Unified Parkinson's Disease Rating Scale (UPDRS) score from gait videos using a convolutional neural network (CNN) model. METHODS: We retrospectively obtained 737 consecutive gait videos of 74 patients with PD and their corresponding neurologist-rated UPDRS scores. We utilized a CNN model for predicting the total UPDRS part III score and four subscores of axial symptoms (items 27, 28, 29, and 30), bradykinesia (items 23, 24, 25, 26, and 31), rigidity (item 22) and tremor (items 20 and 21). We trained the model on 80% of the gait videos and used 10% of the videos as a validation dataset. We evaluated the predictive performance of the trained model by comparing the model-predicted score with the neurologist-rated score for the remaining 10% of videos (test dataset). We calculated the coefficient of determination (R2) between those scores to evaluate the model's goodness of fit. RESULTS: In the test dataset, the R2 values between the model-predicted and neurologist-rated values for the total UPDRS part III score and subscores of axial symptoms, bradykinesia, rigidity, and tremor were 0.59, 0.77, 0.56, 0.46, and 0.0, respectively. The performance was relatively low for videos from patients with severe symptoms. CONCLUSIONS: Despite the low predictive performance of the model for the total UPDRS part III score, it demonstrated relatively high performance in predicting subscores of axial symptoms. The model approximately predicted the total UPDRS part III scores of patients with moderate symptoms, but the performance was low for patients with severe symptoms owing to limited data. A larger dataset is needed to improve the model's performance in clinical settings.

Clinical Characteristics of Patients with Cryptococcal Meningitis in Hokkaido: A Case Series.

We retrospectively reviewed the medical histories, examination results, treatments, and prognoses of nine patients with cryptococcal meningitis who were diagnosed and treated at Hokkaido University Hospital and its affiliated hospitals over the past 10 years. Cryptococcal meningitis can develop even in immunocompetent hosts, and its prognosis is poor owing to diagnostic difficulties and delayed treatment. Although liposomal amphotericin B and oral 5-fluorocytosine are standard therapies, voriconazole or intraventricular administration of amphotericin B may also be considered treatment options for refractory patients. Some patients develop delayed exacerbations owing to immunological mechanisms that require steroid therapy.

The prevalence and incidence of multiple sclerosis over the past 20 years in northern Japan.

OBJECTIVES: The prevalence of multiple sclerosis (MS) in East Asia is thought to be lower than in Western countries. Globally, there is a trend of increasing MS prevalence. We investigated the changes in the prevalence and clinical phenotype of MS in the Tokachi province of Hokkaido in northern Japan, from 2001 to 2021. METHODS: Data processing sheets were sent to all related institutions inside and outside the Tokachi area of Hokkaido island in Japan and were collected from April to May 2021. The prevalence according to the Poser's diagnostic criteria for MS was determined on March 31, 2021. RESULTS: In 2021, the crude MS prevalence in northern Japan was 22.4/100,000 (95% confidence interval, 17.6-28.0). The prevalences of MS standardized by the Japanese national population in 2001, 2006, 2011, 2016, and 2021 were 6.9, 11.5, 15.3, 18.5, and 23.3, respectively. The female/male ratio was 4.0 in 2021, increased from 2.6 in 2001. We checked the prevalence using the 2017 revised McDonald criteria, and found only additional male patient who had not fulfilled Poser's criteria. The age- and sex-adjusted incidence of MS per 100,000 individuals increased from 0.09 in 1980-1984 to 0.99 in 2005-2009; since then, it has remained stable. The proportions of primary-progressive, relapsing-remitting, and secondary-progressive MS types in 2021 were 3%, 82%, and 15%, respectively. CONCLUSION: Our results demonstrated a consistent increase in the prevalence of MS among the northern Japanese over 20 years, particularly in females, and consistently lower rates of progressive MS in northern Japan than elsewhere in the world.

IgG4-Related Peripheral Neuropathy with Unilateral Cervical Nerve Root and Brachial Plexus Swelling: A Case Report.

A 64-year-old man presented with left upper limb weakness and dysesthesia for 4 months. Magnetic resonance imaging demonstrated swelling from the 6th-8th left cervical nerve roots to the left brachial plexus. The serum IgG4 level was elevated (762.7 mg/dL). 18F-FDG-PET showed high uptake in the mediastinal lymph nodes, and biopsy revealed infiltration of IgG4-positive plasma cells. We diagnosed IgG4-related neuropathy, and steroid therapy administration improved the symptoms. IgG4-related disease should be considered in the differential diagnosis of peripheral nerve swellings. If biopsy of the disordered nerves is difficult, lymph nodes or other organs should be considered.

Correlation of active contact location with weight gain after subthalamic nucleus deep brain stimulation: a case series.

BACKGROUND: Weight gain (WG) is a frequently reported side effect of subthalamic deep brain stimulation; however, the underlying mechanisms remain unclear. The active contact locations influence the clinical outcomes of subthalamic deep brain stimulation, but it is unclear whether WG is directly associated with the active contact locations. We aimed to determine whether WG is associated with the subthalamic deep brain stimulation active contact locations. METHODS: We enrolled 14 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation between 2013 and 2019. Bodyweight and body mass index were measured before and one year following the surgery. The Lead-DBS Matlab toolbox was used to determine the active contact locations based on magnetic resonance imaging and computed tomography. We also created sweet spot maps for WG using voxel-wise statistics, based on volume of tissue activation and the WG of each patient. Fluorodeoxyglucose-positron emission tomography data were also acquired before and one year following surgery, and statistical parametric mapping was used to evaluate changes in brain metabolism. We examined which brain regions' metabolism fluctuation significantly correlated with increased body mass index scores and positron emission tomography data. RESULTS: One year after surgery, the body mass index increase was 2.03 kg/m2. The sweet spots for WG were bilateral, mainly located dorsally outside of the subthalamic nucleus (STN). Furthermore, WG was correlated with increased metabolism in the left limbic and associative regions, including the middle temporal gyrus, inferior frontal gyrus, and orbital gyrus. CONCLUSIONS: Although the mechanisms underlying WG following subthalamic deep brain stimulation are possibly multifactorial, our findings suggest that dorsal stimulation outside of STN may lead to WG. The metabolic changes in limbic and associative cortical regions after STN-DBS may also be one of the mechanisms underlying WG. Further studies are warranted to confirm whether dorsal stimulation outside of STN changes the activities of these cortical regions.

Improved Long-Term Survival with Edaravone Therapy in Patients with Amyotrophic Lateral Sclerosis: A Retrospective Single-Center Study in Japan.

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2-64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan-Meier analysis, which revealed that the median survival durations were 49 (9-88) and 25 (8-41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.

Chronic deep brain stimulation reduces cortical ß-γ phase amplitude-coupling in patients with Parkinson's disease.

We compared ß-γ phase amplitude coupling (PAC) before and one year after chronic deep brain stimulation (DBS) in patients with Parkinson's disease using EEG and observed significant post-operative reduction of PAC values. Our findings suggest that the reduction in PAC due to DBS can be observed after chronic stimulation, which is not a transient phenomenon just after the start of DBS.

[A case of paraneoplastic myelopathy associated with anti-CV2/CRMP5 antibodies with small-cell lung cancer].

A 66-year-old woman with small-cell lung cancer and cancer-associated retinopathy with anti-recoverin antibodies presented with subacute paraplegia associated with recurrence of lung cancer. Although a spinal cord MRI did not show any visible lesion, the neurological symptoms and cerebrospinal fluid findings indicated myelitis. Anti-CV2/CRMP5 antibodies were also positive and the patient was diagnosed with paraneoplastic myelopathy. After medication with prednisolone, her neurological symptoms improved and she survived over three years without recurrence of neurological symptoms. In general, paraneoplastic myelopathy is refractory against immunotherapy but in this case, immunotherapy was successful and resulted in long-term survival. We recommend examining anti-neuronal antibodies and choose and continue the appropriate immunotherapy.

Mitigation of Memory Impairment in Ovariectomized Rats Using Garlic Powder Treated with Subcritical Water.

Women with estrogen deficiency are at the risk of suffering from neurological symptoms such as memory impairment. In the present study, we investigated the effect of garlic, Allium sativum L. (Asparagales: Amaryllidaceae), treated with subcritical water on memory impairment in ovariectomized (OVX) rats. OVX rats were administered garlic powder for 84 d. Hippocampus-dependent spatial memory was assessed using the Morris water maze test. Escape latency of the OVX rats increased compared with that of sham-operated rats. The prolonged escape latency of the OVX rats decreased to the level of that of sham-operated rats upon the administration of garlic powder (0.5% in feed). The weights of the body, uterus, and brain were not affected by the garlic powder administration. These results suggest that garlic powder treated with subcritical water mitigates memory impairment in OVX rats.

Hashimoto's encephalopathy mimicking a brain tumor and its pathological findings: A case report.

Hashimoto's encephalopathy is characterized by the presence of anti-thyroid antibodies with no alternative cause. Patients with Hashimoto's encephalopathy present with various clinical symptoms and magnetic resonance imaging (MRI) findings. To our knowledge, this is the first documented report of Hashimoto's encephalopathy with MRI findings mimicking a brain tumor. The patient was a 41-year-old woman with a history of Hashimoto's disease. She experienced gradually worsening Parkinsonism and an MRI revealed a brain tumor-like lesion at the left caudate nucleus. She underwent a brain biopsy that revealed diffuse gliosis and perivascular lymphocyte infiltration with CD3+ T-cell predominance. No pathological signs of a brain tumor were found. Hashimoto's encephalopathy was suspected based on the patient's history and the presence of anti-thyroid antibodies. Her symptoms and the MRI findings improved with glucocorticoid treatment. Although there exist only a few studies on the pathology of Hashimoto's encephalopathy, our findings were consistent with those of previous reports. Our findings suggest cerebral vasculitis as an underlying etiology of Hashimoto's encephalopathy. We also emphasize the importance of considering Hashimoto's encephalopathy as a differential diagnosis of brain tumors.

Tremor during orthostatism as the initial symptom of Machado-Joseph disease.

A 60-year-old man was admitted to our hospital. He had mild tremor in his four extremities when supine or sitting, which was markedly exacerbated when standing. We diagnosed him with Machado-Joseph disease according to the genetic test. His tremor improved with clonazepam, trihexyphenidyl, and a rotigotine patch.

[A retrospective study of the effects of 3,4-diaminopyridine treatment in Lambert-Eaton myasthenic syndrome].

In this independent clinical study, we analyzed retrospectively the clinical features of 9 cases (6 male and 3 female) of Lambert-Eaton myasthenic syndrome that were administered 3,4-diaminopyridine (3,4-DAP). Four cases showed no cancer and 5 cases had small cell lung carcinoma. Seven cases were positive for anti voltage-gated calcium channel antibodies. Activities of daily living (ADL) were improved by 3,4-DAP in 8 cases that showed mainly weakness of the extremities, but did not improve ADL in 1 case with cerebellar ataxia of paraneoplastic cerebellar degeneration (PCD). Seven cases showed autonomic symptoms, and 6 cases were improved with 3,4-DAP. The maintenance dose varied widely among individuals, with a single dose ranging from 10 to 40 mg. Each patient was prescribed a maintenance dose 3 to 7 times a day. The daily dosage ranged from 36 to 100 mg. Two cases showed adverse effects to the treatment. Of those 2 cases, 1 case treated at 45 mg/day discontinued treatment, but another case treated at 100 mg/day reduced the dosage and continued treatment. The administration period was 1 to 149 months. Three cases have continued 3,4-DAP for more than 10 years. Four cases have discontinued 3,4-DAP, with 2 cases discontinuing due to death, 1 case discontinuing due to progression of cancer, and 1 case discontinuing due to an adverse reaction. Our results suggest that 3,4-DAP treatment is effective for weakness and autonomic symptoms, but may be ineffective for ataxia of PCD. Treatment with 3,4-DAP can be tolerated for a long period, but the optimal dosage varies widely among individuals.

Down-regulation of glutamate release from hippocampal neurons by sialidase.

Sialidase, which removes sialic acid residues in sialylglycoconjugates, is essential for hippocampal memory and synaptic plasticity. Enzyme activity of sialidase is rapidly increased in response to neural excitation. Because sialic acid bound to gangliosides such as the tetra-sialoganglioside GQ1b is crucial for calcium signalling and neurotransmitter release, neural activity-dependent removal of sialic acid may affect hippocampal neurotransmission. In the present study, we found that 2-deoxy-2, 3-didehydro-D-N-acetylneuraminic acid (DANA), a sialidase inhibitor, increased expression of ganglioside GQ1b/GT1a in hippocampal acute slices. Extracellular glutamate level in the rat hippocampus measured by using in vivo microdialysis was increased by the sialidase inhibitor 2, 3-dehydro-2-deoxy-N-glycolylneuraminic acid as well as DANA. Synaptic vesicle exocytosis and intracellular Ca2+ increase evoked by high-K+ were also enhanced by DANA in primary cultured hippocampal neurons. Expression of GQ1b/GT1a was rapidly decreased by depolarization with high-K+, suggesting that the increase in sialidase activity by neural excitation is sufficient for cleavage of sialic acid. Our findings indicate that sialidase down-regulates glutamate release from hippocampal neurons via Ca2+ signalling modulation. Neural activity-dependent desialylation by sialidase may be a negative-feedback factor against presynaptic activity.

Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome.

Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer's disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband's pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP.

Sez6l2 regulates phosphorylation of ADD and neuritogenesis.

Increasing evidence shows that immune-mediated mechanisms may contribute to the pathogenesis of central nervous system disorders including cerebellar ataxias, as indicated by the aberrant production of neuronal surface antibodies. We previously reported a patient with cerebellar ataxia associated with production of a new anti-neuronal antibody, anti-seizure-related 6 homolog like 2 (Sez6l2). Sez6l2 is a type 1 membrane protein that is highly expressed in the hippocampus and cerebellar cortex and mice lacking Sez6l2 protein family members develop ataxia. Here we used a proteomics-based approach to show that serum derived from this patient recognizes the extracellular domain of Sez6l2 and that Sez6l2 protein binds to both adducin (ADD) and glutamate receptor 1 (GluR1). Our results indicate that Sez6l2 is one of the auxiliary subunits of the AMPA receptor and acts as a scaffolding protein to link GluR1 to ADD. Furthermore, Sez6l2 overexpression upregulates ADD phosphorylation, whereas siRNA-mediated downregulation of Sez612 prevents ADD phosphorylation, suggesting that Sez6l2 modulates AMPA-ADD signal transduction.

Validity and reliability of a pilot scale for assessment of multiple system atrophy symptoms.

BACKGROUND: Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder for which brief yet sensitive scale is required in order for use in clinical trials and general screening. We previously compared several scales for the assessment of MSA symptoms and devised an eight-item pilot scale with large standardized response mean [handwriting, finger taps, transfers, standing with feet together, turning trunk, turning 360°, gait, body sway]. The aim of the present study is to investigate the validity and reliability of a simple pilot scale for assessment of multiple system atrophy symptoms. METHODS: Thirty-two patients with MSA (15 male/17 female; 20 cerebellar subtype [MSA-C]/12 parkinsonian subtype [MSA-P]) were prospectively registered between January 1, 2014 and February 28, 2015. Patients were evaluated by two independent raters using the Unified MSA Rating Scale (UMSARS), Scale for Assessment and Rating of Ataxia (SARA), and the pilot scale. Correlations between UMSARS, SARA, pilot scale scores, intraclass correlation coefficients (ICCs), and Cronbach's alpha coefficients were calculated. RESULTS: Pilot scale scores significantly correlated with scores for UMSARS Parts I, II, and IV as well as with SARA scores. Intra-rater and inter-rater ICCs and Cronbach's alpha coefficients remained high (> 0.94) for all measures. CONCLUSION: The results of the present study indicate the validity and reliability of the eight-item pilot scale, particularly for the assessment of symptoms in patients with early state multiple system atrophy.

[Utility of Intraoperative Catheter Myelography during Intrathecal Baclofen Pump Implantation:Report of 2 Cases].

We report two patients in whom the intrathecal baclofen(ITB)catheter was located in the subdural space, although we had confirmed good outflow of spinal fluid from the spinal catheter. Patient 1 was a woman in her 30s with spastic quadriplegia due to subarachnoid hemorrhage. An ITB pump was implanted, and a good outflow of spinal fluid from the spinal catheter was observed during the surgery. Postoperatively, her spasticity did not improve. Catheter myelography revealed that the spinal catheter was located in the subdural space. Using intraoperative catheter myelography, we corrected the position of the catheter. Patient 2 was a man in his 20s diagnosed with adrenoleukodystrophy. An ITB therapy was performed to improve his spastic gait. Intraoperative catheter myelography showed that the spinal catheter was located in the subdural space, although there was good outflow of spinal fluid from the catheter. Our experience suggests that the outflow of spinal fluid alone should not be used to determine the location of the spinal catheter. Intraoperative catheter myelography is useful for the correct placement of the spinal catheter in the subarachnoid space.