[Foot drop and cyclic sensory disturbance of the right lower limb due to endometriosis].

We report the case of a 40-year-old woman, with endometriosis, who presented with a history of foot drop and cyclic sensory disturbance of the right lower limb. She was initially diagnosed with lumbar disc herniation. Neurological examination revealed muscle weakness and sensory disturbance associated with the right sciatic nerve. Nerve conduction studies revealed a low amplitude sensory nerve action potential in the right superficial fibular and sural nerves. Pelvic magnetic resonance imaging revealed an endometriotic cyst in the right ovary, and an endometriotic lesion extending from the right ovary, pelvis, and the right sciatic nerve. Though her symptoms moderately improved with hormonal therapy, the foot drop remained. Our case and previous reports suggest that endometriosis with sciatic neuropathy shows cyclic neurological symptoms during menstruation, with a higher incidence on the right extremity. This case highlights that endometriosis should be considered as a potential differential diagnosis in women of reproductive age with sciatic nerve dysfunction. Its cyclic neurological manifestations should be investigated.

Clinical Features of Parkinson's Disease in Patients with Early-Onset Freezing of Gait.

Background: Freezing of gait (FOG) is an important symptom that can impair activities of daily living in patients with Parkinson's disease (PD). However, its pathogenic mechanism is largely unknown. The aim of the present study was to elucidate the clinical characteristics of newly diagnosed and levodopa-naïve patients with PD who present with FOG. Methods: A total of 53 patients with untreated PD (29 men and 24 women) within 2 years of disease onset were included in the study. Using item 3 of the Freezing of Gait Questionnaire (FOG-Q), patients were classified as "freezers" and "nonfreezers" and compared for cognitive function, depressive symptoms, apathy, olfactory function, motor severity, gait parameters, and daily physical activity. We also assessed the relationship between FOG severity (total score of items 3-6 on the FOG-Q) and various clinical parameters. Results: The FOG was reported by 8 (15%) patients with PD. The Apathy Scale score (p=0.018), Modified Hoehn and Yahr stage (p < 0.001), Unified Parkinson's Disease Rating Scale part III score (p < 0.001), and postural instability and gait disorder score (p < 0.001) were significantly higher, and the mean gait acceleration amplitude (p=0.006) was significantly lower in freezers compared to that in nonfreezers. However, there was no significant correlation between FOG severity and these clinical parameters. There was also no significant difference in cognitive function, depressive symptoms, and olfactory function between the two groups. Daily physical activity was significantly lower in freezers than that in nonfreezers. Conclusions: Since FOG develops soon after PD onset, the study findings suggest that the FOG might be associated with the severity of apathy, motor symptoms, and in particular, gait disturbance.

[A case of methotrexate-associated diffuse large B-cell lymphoma with splenial lesions of the corpus callosum on brain MRI after complete remission with chemotherapy].

An 86-year-old woman in a wheelchair was accompanied by her husband and son as she visited our outpatient clinic due to disturbed consciousness and fever. Twenty-seven years earlier, she had been diagnosed with rheumatoid arthritis and had been treated with methotrexate (MTX) and low-dose prednisolone (PSL). She stopped taking MTX four years previously when she was diagnosed with diffuse large B cell lymphoma of the paranasal sinus. Her lymphoma went into remission after six cycles of systemic immunochemotherapy. MRI after hospitalization revealed a lesion in the splenium of the corpus callosum that was hyperintense on diffusion-weighted imaging and which had low apparent diffusion coefficient values. An analysis of the cerebrospinal fluid revealed no atypical cells. The MRI findings were atypical, but her consciousness disturbance improved, leading to the diagnosis of mild encephalitis/encephalopathy with a reversible splenial lesion, which would be associated with a transient consciousness disturbance with a good course. However, her consciousness worsened over the next 3 weeks. One month later, a contrast-enhanced MRI showed an enlarged lesion in the callosum as well as new lesions, and the diagnosis of secondary CNS lymphoma was made. Brain biopsy is often not feasible. Less invasive and highly accurate diagnostic methods are needed, such as the identification of a spinal fluid tumor marker.

[Usefulness of an anti-mouse cerebellar tissue-derived antigen antibody test in predicting immunotherapy efficacy in patients with idiopathic cerebellar ataxia].

BACKGROUND: Autoimmune cerebellar ataxia (AICA) is a general term for diseases in which the cerebellum is damaged by an autoimmune mechanism. For the diagnosis of the AICA, anti-thyroid antibodies (anti-thyroid peroxidase antibody and anti-thyroglobulin antibody), anti-glutamic acid decarboxylase (GAD) antibodies, and anti-gliadin antibodies are measured. Immunotherapy is known to be effective for AICA, but some patients with effective immunotherapy lack autoantibodies associated with cerebellar ataxia. The purpose of this study was to clarify whether the effectiveness of immunotherapy in patients with suspected AICA could be predicted by anti-mouse cerebellar tissue-derived antigen antibody tests. METHODS: This study was conducted on 25 patients with idiopathic cerebellar ataxia (excluding multiple system atrophy, hereditary spinocerebellar degeneration, cancer-bearing patients, and patients taking phenytoin) who received immunotherapy from 2005 to 2016 at Tokyo Medical University Hachioji Medical Center. The patients were suspected of having AICA because they were positive for cerebellar ataxia-related autoantibodies (anti-thyroid antibody, anti-GAD antibody, anti-gliadin antibody, or anti-transglutaminase 6 antibody) or other autoantibodies. Antibodies that bind to mouse cerebellar tissue-derived antigens were defined as "anti-mouse cerebellar tissue-derived antigen antibodies" in this study, and their IgG-class antibodies were comprehensively measured using a slot blot. RESULTS: Anti-mouse cerebellar tissue-derived antigen antibody test results were correlated with immunotherapy efficacy. Furthermore, the combination of anti-mouse cerebellar tissue-derived antigen and anti-GAD antibody tests could predict the effectiveness of immunotherapy with 83% sensitivity and 100% specificity, while the combination of the anti-mouse cerebellar tissue-derived antigen, anti-GAD, and anti-gliadin (IgA class) antibody tests could predict the effectiveness of immunotherapy with 94% sensitivity and 86% specificity. CONCLUSION: Anti-mouse cerebellar tissue-derived antigen antibody tests could help to provide useful information for immunotherapy administration to patients with idiopathic cerebellar ataxia suspected to be AICA.

Parkinson's disease with a typical clinical course of 17 years overlapped by Creutzfeldt-Jakob disease: an autopsy case report.

BACKGROUND: Late-stage Parkinson's disease (PD) often presents with neuropsychiatric symptoms such as dementia, psychosis, excessive daytime sleepiness, apathy, depression, and anxiety. However, neuropsychiatric symptoms are the cardinal features of Creutzfeldt-Jakob disease (CJD), raising the possibility that CJD may be an overlooked condition when it accompanies late-stage PD. CASE PRESENTATION: We describe a female autopsy case of PD with a typical clinical course of 17 years, in which CJD overlapped with PD during the final year of the patient's life. The patient died aged 85 years. Neuropathological features included widespread Lewy body-related α-synucleinopathy predominantly in the brainstem and limbic system, as well as the typical pathology of methionine/methionine type 1 CJD in the brain. CONCLUSIONS: Our case demonstrates the clinicopathological co-occurrence of PD and CJD in a sporadic patient. The possibility of mixed pathology, including prion pathology, should be taken into account when neuropsychiatric symptoms are noted during the disease course of PD.

Persistent Hemichorea as a Preceding Symptom of Cerebral Infarction Due to Middle Cerebral Artery Stenosis.

We herein report an 84-year-old woman with right middle cerebral artery (MCA) stenosis who presented with persistent left hemichorea preceding cerebral infarction. She visited our hospital on day 9 after the hemichorea onset. Magnetic resonance imaging (MRI) showed no acute cerebral infarction. Magnetic resonance angiography revealed right MCA stenosis. Her hemichorea persisted for 19 days and subsequently disappeared. On day 21, she developed left hemiplegia. Repeat MRI revealed a cerebral infarction in the right putamen. MCA stenosis can present with persistent hemichorea, even in the absence of cerebral infarction. Persistent hemichorea with MCA stenosis may presage cerebral infarction.

Relationship between 123I-FP-CIT-SPECT and motor severity in drug-naive patients with Parkinson's disease.

INTRODUCTION: Although functional imaging is useful for the diagnosis and pathophysiological evaluation of Parkinson's disease (PD), little is known about the relationship between functional imaging findings and PD clinical features. The objective of this study was to determine the relationship between 123I-FP-CIT-SPECT findings and motor symptoms, in particular gait disturbance. METHODS: The study included 46 drug-naive patients with early-stage PD. The specific binding ratios (SBRs) in the striatum and its subregions, namely anterior/posterior putamen and caudate nucleus, were calculated in patients who underwent 123I-FP-CIT-SPECT. Motor symptoms were evaluated using the modified Hoehn and Yahr (HY) stage and the Unified Parkinson's Disease Rating Scale (UPDRS) part III. Gait disturbance was evaluated by the mean gait cycle duration and the mean gait acceleration amplitude measured with a wearable sensor. RESULTS: The mean SBRs of the striatum and anterior putamen were significantly associated with the modified HY stage and UPDRS part III score. The mean SBR of the caudate nucleus was significantly associated with the UPDRS part III score. The mean striatal SBR was also significantly associated with the mean gait cycle duration and mean gait acceleration amplitude. CONCLUSION: The mean striatal SBR, as determined by 123I-FP-CIT-SPECT, was significantly associated with motor severity and gait severity in drug-naive patients with PD.

Cerebral Infarction and Myalgia in a 75-year-old Man with Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare condition of systemic vasculitis of small to medium-sized blood vessels. We herein report the case of a 75-year-old man who presented with hemiplegia on his right side due to cerebral infarction following myalgia and a high fever. He had no history of asthma or allergic rhinitis. He was diagnosed with EGPA based on the presence of eosinophilia, sinusitis suggested by magnetic resonance imaging, and muscle pathology. His hemiplegia improved rapidly after corticosteroid therapy. This case suggests that EGPA should be a differential diagnosis of cerebral infarction with myalgia and eosinophilia.

Analysis of non-invasive gait recording under free-living conditions in patients with Parkinson's disease: relationship with global cognitive function and motor abnormalities.

BACKGROUND: We investigated the gait characteristics of patients with Parkinson's disease (PD), under free-living conditions, using a wearable device, and assessed their relationships with global cognitive function and motor abnormalities. METHODS: The study subjects comprised patients with PD aged < 80 years, with a Mini-Mental State Examination (MMSE) score of ≥20, free of any motor complications. A wearable sensor with a built-in tri-axial accelerometer was waist-mounted on each patient, and continuous, 24-h records were obtained. The mean gait cycle duration and mean gait acceleration amplitude, under free-living conditions, were computed and analyzed to determine their relationship with disease duration, MMSE score, Unified Parkinson's Disease Rating Scale (UPDRS) Part III score, and postural instability and gait difficulty (PIGD) score. RESULTS: The study included 106 consecutive patients with PD. The mean gait cycle duration was 1.18 ± 0.12 s, which was similar to that of the normal controls. However, the mean gait acceleration amplitude of PD patients (1.83 ± 0.36 m/s2) was significantly lower than that of the control (p < 0.001). In PD patients, the mean gait acceleration amplitude correlated with the MMSE (ß = 0.197, p = 0.028), UPDRS Part III (ß = - 0.327, p < 0.001), and PIGD (ß = - 0.235, p = 0.008) scores. CONCLUSIONS: The gait rhythm of PD patients is preserved at levels similar to those of normal subjects. However, the mean gait acceleration amplitude was significantly reduced in patients with PD. The results indicate that gait acceleration amplitude correlates with the severity of motor disorders and global cognitive function.

Assessment and Rating of Motor Cerebellar Ataxias With the Kinect v2 Depth Sensor: Extending Our Appraisal.

Current assessment of patients with cerebellar disorders is based on conventional neurological examination that is dependent on subjective judgements. Quantitative measurement of cerebellar ataxias (CAs) is essential for assessment of evidence-based treatments and the monitoring of the progress or recovery of diseases. It may provide us a useful tool to navigate future treatments for ataxia. We developed a Kinect v2. sensor system with a novel algorithm to measure and evaluate movements for two tests of Scale for the Assessment and Rating of Ataxia (SARA): the nose-finger test and gait. For the nose-finger test, we evaluated and compared accuracy, regularities and smoothness in the movements of the index finger and the proximal limbs between cerebellar patients and control subjects. For the task of walking, we evaluated and compared stability between the two groups. The precision of the system for evaluation of movements was smaller than 2 mm. For the nose-finger test, the mildly affected patients tended to show more instability than the control subjects. For a severely affected patient, our system quantified the instability of movements of the index finger using kinematic parameters, such as fluctuations and average speed. The average speed appears to be the most sensitive parameter that contrasts between patients with CAs and control subjects. Furthermore, our system also detected the adventitious movements of more proximal body parts, such as the elbow, shoulder and head. Assessment of walking was possible only in patients with mild CAs. They demonstrated large sways and compensatory wide stances. These parameters appeared to show higher accuracy than SARA. This examiner-independent device measures movements of the points of interest of SARA more accurately than eye and further provides additional information about the ataxic movements (e.g., the adventitious movements of the elbow, shoulder and head in the nose-finger test and the wide-based walking with large oscillation in the gait task), which is out of the scope of SARA. Our new system enables more accurate scoring of SARA and further provides additional information that is not currently evaluated with SARA. Therefore, it provides an easier, more accurate and more systematic description of CAs.

Association of daily physical activity with cognition and mood disorders in treatment-naive patients with early-stage Parkinson's disease.

To determine the association of daily physical activity with cognition, mood disorders, and olfactory function in treatment-naive patients with early-stage Parkinson's disease (PD). The study subjects were 52 treatment-naive patients with early-stage PD (< 80 years). Daily physical activity was measured using a wearable sensor with a built-in triaxial accelerometer, and its association with cognition [mini-mental state examination (MMSE), clock-drawing test (CDT), frontal assessment battery (FAB), and behavioral assessment of the dysexecutive syndrome (BADS)], depressive symptoms [Beck Depression Inventory-Second Edition (BDI-II)], apathy [Starkstein Apathy Scale (AS)], and olfactory function [Odor Stick Identification Test for the Japanese (OSIT-J)] was analyzed using multiple linear regression after adjustment for age, sex, and education status. The daily physical activity (0.42 ± 0.11 m/s2) of the PD group was significantly lower than that of healthy controls (p < 0.001). Moreover, the daily physical activity of the PD group was significantly associated with FAB (ß = 0.337, p = 0.027) and BADS (ß = 0.374, p = 0.017) scores, but not with MMSE, CDT, BDI-II, AS, and OSIT-J scores. The daily physical activity is significantly reduced in treatment-naive patients with early-stage PD, and the low activity correlates with frontal/executive function.

[A case of meningeal carcinomatosis mimicking subarachnoid hemorrhage on MRI].

We report a case of meningeal carcinomatosis that needed to be distinguished from subarachnoid hemorrhage. A 67-year-old female with acute severe headache was admitted to a previous hospital. Since high intensity signal was detected within the parietal cerebral sulci on the right side on brain FLAIR MRI, cerebral angiography was performed due to suspicion of subarachnoid hemorrhage. However, no vascular abnormality was observed. Then, cerebral spinal fluid was collected, which showed an increase in cell count, suggesting meningitis. She was transferred to our hospital for evaluation of neurological disease. After admission to our hospital, there was an episode of hematemesis. Upper gastrointestinal endoscopy was performed, and advanced gastric cancer was found. She was diagnosed as having meningeal carcinomatosis due to gastric cancer. Meningeal carcinomatosis should be considered in addition to subarachnoid hemorrhage when a patient with acute headache shows high intensity signal within the cerebral sulci on brain FLAIR MRI.

Secondary parkinsonism.

Although many disorders are included in secondary parkinsonism, the mechanisms underlying parkinsonism vary and have yet to be elucidated. Herein, we introduced a group of diseases included among the forms of secondary parkinsonism and provide overviews of clinically significant drug-induced parkinsonism (DIP), vascular parkinson- ism (VP), and idiopathic normal pressure hydrocephalus (iNPH) with a focus on pathophysiology and symptoms. Although DIP has the highest frequency among the forms of secondary parkinsonism, it is overlooked in many patients due to lack of knowledge about drugs by the prescribing physicians. Both VP and iNPH present with "lower body parkinsonism, " showing the characteristic gait disturbance. DIP and iNPH are treatable, highlighting the importance of early diagnosis and treatment intervention.

Prevalence of Autoantibodies and the Efficacy of Immunotherapy for Autoimmune Cerebellar Ataxia.

OBJECTIVE: Autoimmune cerebellar ataxias were recently reported to be treatable. However, the proportion of patients with cortical cerebellar atrophy of unknown etiology with autoimmune-associated cerebellar ataxia and the actual effectiveness of immunotherapy in these diseases remain unknown. METHODS: We measured the level of autoantibodies (including anti-gliadin antibody, anti-glutamic acid decarboxylase (GAD) antibody, and anti-thyroid antibody) in 58 Japanese patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, cancer, or those who were receiving phenytoin, and the efficacy of immunotherapy was assessed. RESULTS: Thirty-one of 58 (53%) patients were positive for anti-GAD antibody, anti-gliadin antibody, or anti-thyroid antibody. Seven of the 12 anti-gliadin antibody-positive patients, three of the four anti-GAD antibody-positive patients, and three of the six anti-thyroid antibody-positive patients responded well to immunotherapy, indicating that 59% of patients with ataxia-associated antibody-positive cerebellar ataxia undergoing immunotherapy responded well. CONCLUSION: Some patients with cerebellar ataxia have autoimmune conditions and diagnosing autoimmune cerebellar ataxia is therefore an important component in the care of patients with this disease entity.

Storage of washed platelets in BRS-A platelet additive solutions based on two types of clinically available bicarbonated Ringer's solutions with different electrolyte concentrations.

BACKGROUND: In Japan, no platelet (PLT) additive solutions (PASs) are officially approved for clinical use although blood centers often receive requests for washed PLTs to reduce adverse reactions. Recently, we developed a novel PAS called BRS-A based on clinically available bicarbonated Ringer's solution (BRS), Bicanate and acid-citrate-dextrose formula A (ACD-A), which has been shown to maintain the in vitro properties of PLTs in the condition of <5% residual plasma during 7-day storage. The aim of this study was to evaluate whether another clinically available BRS, Bicarbon with different electrolyte concentrations can be used as a PAS. STUDY DESIGN AND METHODS: Two types of BRS-As were prepared by adding 25 mL of ACD-A to 500 mL of Bicanate or Bicarbon BRSs. Bicanate-based BRS-A and Bicarbon-based BRS-A contain 0.9 or 0.5 mmol/L of magnesium chloride, 95.2 or 100.1 mmol/L of sodium chloride, 4.2 or 5.1 mmol/L of trisodium citrate, and 26.6 or 23.8 mmol/L of sodium bicarbonate, respectively; the other components were identical. Apheresis PLTs stored in these solutions with less than 5% plasma for 7-day storage were compared with regard to their in vitro properties. RESULTS: The pH levels of all units were above 7 throughout storage. The mean PLT volume, hypotonic shock response, glucose consumption, lactate production, swirling, and CD62P and CD42b expression were similar during 7-day storage. The bicarbonate levels in Bicarbon-based BRS-A were lower than those in Bicanate-based BRS-A. CONCLUSION: Differences in concentrations of electrolytes such as magnesium, sodium, citrate, and bicarbonate salts in BRS-A do not affect the in vitro properties of PLTs during 7-day storage. These results indicate that the use of another type of BRS-A based on Bicarbon as a PAS is feasible. Thus, BRS-A can be used in hospitals that do not stock Bicanate but have Bicarbon.

Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

Gluten ataxia in Japan.

Gluten ataxia, a type of cerebellar ataxia caused by exposure to gluten in sensitive patients, has been considered common in the USA and Europe, and rare in Asia. We measured anti-deamidated gliadin peptide (DGP) antibody levels in 49 patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, or cancer, as well as those who were receiving oral administration of phenytoin. Anti-DGP antibody was positive in eight (16.3 %) patients, five of these patients were positive only for IgA, one was positive for both IgG and IgA, and two were positive only for IgG antibody. Intravenous immunoglobulin was administered to five of the eight patients, and was markedly effective in one, moderately effective in two, and ineffective in two. Steroid therapy was administered to four patients, but none had an apparent response. Ataxia symptoms improved in one patient treated with a gluten-free diet only. Although it had been thought to be extremely rare in Asia, we speculate that more than 10 % of cerebellar ataxia patients in Japan currently have gluten ataxia; therefore, measuring anti-DGP antibody or anti-gliadin antibody in cerebellar ataxia patients in Asia is important.

[The utility of voxel-based morphometry in the diagnosis of spinocerebellar degeneration].

We evaluated atrophic sites in the brainstem and cerebellum in the patients with spinocerebellar degeneration by using voxel-based morphometry (VBM). Gray matter atrophy was found extensively in both the cerebellar hemispheres and vermis of subjects presenting the cerebellar variant of multiple system atrophy (MSA-C; n=9). In addition, remarkable white matter atrophy was observed in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. In contrast, gray matter atrophy was not apparent in the cerebellar hemispheres or vermis of subjects in the SCA3 group (n=6), whereas intense white matter atrophy was visible in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. White matter atrophy was also observed in the brainstem and surrounding the dentate nucleus in both cases of dentatorubral-pallidoluysian atrophy (DRPLA) (n=2), whereas gray matter atrophy of the cerebellum was not remarkable. In both the SCA6 group (n=3) and the SCA31 group (n=2), gray matter atrophy was prominent in the cerebellar hemispheres and vermis; however, white matter atrophy was not found in the middle cerebellar peduncle and brainstem, whereas symmetric atrophy of white matter was found in the vicinity of the dentate nucleus. In each of these diseases, VBM findings were consistent with the pathological findings; therefore, VBM can be considered a useful tool for the diagnosis of spinocerebellar degeneration.