Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists' perspectives.

BACKGROUND: Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists' current practices and experiences in delivering the diagnosis of MSA. METHODS: We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique. RESULTS: Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA. CONCLUSIONS: Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient's personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term "sudden death" in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.

Digital Motor Biomarkers of Cerebellar Ataxia Using an RGB-Depth Camera-Based Motion Analysis System.

This study aimed to identify quantitative biomarkers of motor function for cerebellar ataxia by evaluating gait and postural control using an RGB-depth camera-based motion analysis system. In 28 patients with degenerative cerebellar ataxia and 33 age- and sex-matched healthy controls, motor tasks (short-distance walk, closed feet stance, and stepping in place) were selected from a previously reported protocol, and scanned using Kinect V2 and customized software. The Clinical Assessment Scale for the Assessment and Rating of Ataxia (SARA) was also evaluated. Compared with the normal control group, the cerebellar ataxia group had slower gait speed and shorter step lengths, increased step width, and mediolateral trunk sway in the walk test (all P < 0.001). Lateral sway increased in the stance test in the ataxia group (P < 0.001). When stepping in place, the ataxia group showed higher arrhythmicity of stepping and increased stance time (P < 0.001). In the correlation analyses, the ataxia group showed a positive correlation between the total SARA score and arrhythmicity of stepping in place (r = 0.587, P = 0.001). SARA total score (r = 0.561, P = 0.002) and gait subscore (ρ = 0.556, P = 0.002) correlated with mediolateral truncal sway during walking. These results suggest that the RGB-depth camera-based motion analyses on mediolateral truncal sway during walking and arrhythmicity of stepping in place are useful digital motor biomarkers for the assessment of cerebellar ataxia, and could be utilized in future clinical trials.

Delayed Appearance of Brain Magnetic Resonance Imaging Abnormalities in a Patient with Glial Fibrillary Acidic Protein Astrocytopathy.

Recent studies have reported that autoantibodies against glial fibrillary acidic protein (GFAP), a major cytoskeletal protein expressed in astrocytes, can lead to GFAP astrocytopathy, an autoimmune central nervous system inflammatory disease. We herein report the unique case of a 59-year-old Japanese woman with GFAP astrocytopathy who presented with characteristic symptoms, including signs of meningeal irritation, cerebellar ataxia, and bladder/rectal dysfunction, in the absence of specific findings on initial brain magnetic resonance imaging (MRI). The patient exhibited new abnormal changes mainly in the brainstem on follow-up MRI, illustrating the need to recognize that MRI abnormalities may appear later in GFAP astrocytopathy.

Dopaminergic Correlates of Regional Cerebral Blood Flow in Parkinsonian Disorders.

BACKGROUND: Cerebral blood flow (CBF) and dopamine transporter (DAT) images are clinically used for the differential diagnosis of parkinsonian disorders. OBJECTIVES: This study aimed to examine the correlation of CBF with striatal DAT in patients with Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and evaluate the diagnostic power of DAT-correlated CBF in PD through machine learning with each imaging modality alone or in combination. METHODS: Fifty-eight patients with PD and 71 with APS (24 with multiple system atrophy, 21 with progressive supranuclear palsy, and 26 with corticobasal syndrome) underwent 123 I-IMP and 123 I-FP-CIT single-photon emission computed tomography. Multiple regression analyses for CBF and striatal DAT binding were conducted on each group. PD probability was predicted by machine learning and receiver operating characteristic curves. RESULTS: The PD group showed more affected striatal DAT binding positively correlated with the ipsilateral prefrontal perfusion and negatively with the bilateral cerebellar perfusion. In corticobasal syndrome, striatal DAT binding positively correlated with the ipsilateral prefrontal perfusion and negatively with the contralateral precentral perfusion. In Richardson's syndrome, striatal DAT binding positively correlated with perfusion in the ipsilateral precentral cortex and basal ganglia. Machine learning showed that the combination of CBF and DAT was better for delineating PD from APS (area under the curve [AUC] = 0.87) than either CBF (0.67) or DAT (0.50) alone. CONCLUSIONS: In PD and four-repeat tauopathy, prefrontal perfusion was related to ipsilateral nigrostriatal dopaminergic function. This dual-tracer frontostriatal relationship may be effectively used as a diagnostic tool for delineating PD from APS. © 2022 International Parkinson and Movement Disorder Society.

Cultural bias in motor function patterns: Potential relevance for predictive, preventive, and personalized medicine.

BACKGROUND: Quantification of motor performance has a promising role in personalized medicine by diagnosing and monitoring, e.g. neurodegenerative diseases or health problems related to aging. New motion assessment technologies can evolve into patient-centered eHealth applications on a global scale to support personalized healthcare as well as treatment of disease. However, uncertainty remains on the limits of generalizability of such data, which is relevant specifically for preventive or predictive applications, using normative datasets to screen for incipient disease manifestations or indicators of individual risks. OBJECTIVE: This study explored differences between healthy German and Japanese adults in the performance of a short set of six motor tests. METHODS: Six motor tasks related to gait and balance were recorded with a validated 3D camera system. Twenty-five healthy adults from Chiba, Japan, participated in this study and were matched for age, sex, and BMI to a sample of 25 healthy adults from Berlin, Germany. Recordings used the same technical setup and standard instructions and were supervised by the same experienced operator. Differences in motor performance were analyzed using multiple linear regressions models, adjusted for differences in body stature. RESULTS: From 23 presented parameters, five showed group-related differences after adjustment for height and weight (R 2 between .19 and .46, p<.05). Japanese adults transitioned faster between sitting and standing and used a smaller range of hand motion. In stepping-in-place, cadence was similar in both groups, but Japanese adults showed higher knee movement amplitudes. Body height was identified as relevant confounder (standardized beta >.5) for performance of short comfortable and maximum speed walks. For results of posturography, regression models did not reveal effects of group or body stature. CONCLUSIONS: Our results support the existence of a population-specific bias in motor function patterns in young healthy adults. This needs to be considered when motor function is assessed and used for clinical decisions, especially for personalized predictive and preventive medical purposes. The bias affected only the performance of specific items and parameters and is not fully explained by population-specific ethnic differences in body stature. It may be partially explained as cultural bias related to motor habits. Observed effects were small but are expected to be larger in a non-controlled cross-cultural application of motion assessment technologies with relevance for related algorithms that are being developed and used for data processing. In sum, the interpretation of individual data should be related to appropriate population-specific or even better personalized normative values to yield its full potential and avoid misinterpretation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00236-3.

Dysfunction of the left angular gyrus may be associated with writing errors in ALS.

Background: Language dysfunction is a feature of cognitive impairment in amyotrophic lateral sclerosis (ALS) that may compromise communication. Objective: To elucidate language dysfunction in patients with ALS and its relationship with other neuropsychological tests and to identify the brain regions associated with this dysfunction using perfusion image. Methods: Overall, 37 patients with ALS were included in this study. Their neuropsychological function was investigated using the Western Aphasia Battery (WAB), Frontal Assessment Battery and Behavioral Assessment of the Dysexecutive Syndrome. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography was used to examine regional cerebral blood flow and its relationship with WAB scores was investigated using multiple regression analyses, controlled for age, sex and years of education. Results: Frequency of language abnormality in ALS was 8.5% for spontaneous speech, 25.7% for auditory verbal comprehension, 8.8% for repetition, 14.7% for naming, 17.6% for reading and 51.4% for writing. The writing error was mainly omission and substitution of kana letters. Executive tests were correlated with naming (r > 0.5, p < 0.001) and reading (r > 0.4, p < 0.01) scores. With respect to the writing sub-test, positive perfusional relationship was only detected in the left angular gyrus. Conclusions: The left angular gyrus is the region associated with the writing errors observed in ALS.

Gerstmann's Syndrome in a Patient Double-positive for Antibodies against the N-methyl-D-aspartate Receptor and NH2-terminal of α-enolase.

We herein report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis concurrent with NH2-terminal of α-enolase (NAE) antibodies. A 36-year-old Japanese woman presented with Gerstmann's syndrome followed by jerky involuntary movements, seizure, autonomic instability, and consciousness disturbance. NAE antibodies were detected in the serum; however, NMDAR antibodies were identified in the cerebrospinal fluid with a cell-based assay, confirming the diagnosis of anti-NMDAR encephalitis. This case highlights the fact that Gerstmann's syndrome can be a manifestation of anti-NMDAR encephalitis and that NAE may be identified concurrently with NMDAR antibodies, suggesting that the diagnosis of Hashimoto encephalopathy requires the reasonable exclusion of alternative diagnoses, including anti-NMDAR encephalitis.

Low muscle quality in Japanese type 2 diabetic patients with visceral fat accumulation.

BACKGROUND: Although obesity-related type 2 diabetes mellitus (T2DM) and sarcopenia in the elderly have been increasing worldwide, the associations among visceral fat accumulation, skeletal muscle indices (mass, strength, and quality) and cardiovascular diseases in T2DM remain poorly investigated. METHODS: We enrolled 183 Japanese T2DM inpatients (126 men, 57 women; mean age 64.7 ± 12.6 years, ± SD). The estimated-visceral fat area (eVFA) and skeletal muscle mass were measured by each device using bioelectrical impedance analysis method. We also measured grip strength by dynamometer and motor nerve conduction velocity (MCV). We analyzed the difference in skeletal muscle indices between T2DM patients with and without visceral fat accumulation, and examined the impact of skeletal muscle indices on cardiovascular diseases in patients with visceral fat accumulation. RESULTS: The prevalence of sarcopenia defined by the Consensus of Asian Working Group for Sarcopenia and low skeletal muscle mass were both lower in the visceral fat accumulation (+) group than in (-) group. However, the prevalence of weak hand grip strength was similar in the visceral fat accumulation (-) and (+) groups, indicating that considerable patients with visceral fat accumulation had weak grip strength in spite of fair skeletal muscle mass. Muscle quality [grip strength (kg)/arm muscle mass (kg)] was significantly lower in patients with visceral fat accumulation. Multiple regression analysis identified eVFA, MCV and sex as significant and independent determinants of muscle quality. In visceral fat accumulation (+) group, the patients with low muscle quality had longer duration of diabetes, lower eGFR, higher serum adiponectin, lower MCV and higher prevalence of cardiovascular diseases, compared to the patients with high muscle quality. Finally, sex- and age-adjusted models showed significant association between low muscle quality and cardiovascular diseases in all subjects (odds ratio 2.28, p = 0.012), especially in patients with visceral fat accumulation (odds ratio 2.72, p = 0.018). CONCLUSIONS: T2DM patients with visceral fat accumulation had low muscle quality, and patients with low muscle quality were more affected with cardiovascular diseases.

Different pathological phenotypes of autoimmune gastritis induced by neonatal thymectomy between BALB/c and (BALB/c x DBA/2) F1 mice: role of eosinophils in hypertrophic autoimmune gastritis.

BACKGROUND: A unique pathological feature of murine autoimmune gastritis (AIG) is its pronounced mucosal hypertrophy, which is different from human type A chronic atrophic gastritis with pernicious anemia. The aim of this study was to clarify the mechanism of gastric hypertrophy in murine AIG, especially in relation to inflammatory cells infiltrating the gastric mucosa. METHODS: Neonatally thymectomized (NTx) BALB/c and (BALB/c x DBA/2) F1 mice with gastritis were examined histologically and serologically. The T-helper (Th1/Th2) immune balance in the spleen was evaluated by intracellular cytokine staining for interferon-gamma and a flow-cytometric beads array for several cytokines. Additionally, NTx AIG BALB/c mice were orally administered an H(2)-blocker to decrease eosinophils. RESULTS: NTx AIG BALB/c mice exhibited gastritis without stomach hypertrophy at 2 months of age, and developed gastritis with mucous gland hypertrophy accompanied by eosinophil infiltration at 6 months of age. In contrast, NTx AIG (BALB/c x DBA/2) F1 mice displayed gastritis with neither stomach hypertrophy nor eosinophil infiltration even at the age of 6 months. Upregulation of interleukin-4 and granulocyte-macrophage colony-stimulating factor in the spleen was observed in BALB/c mice but not in (BALB/c x DBA/2) F1 mice. Additionally, some NTx AIG BALB/c mice did not show gastric hypertrophy or eosinophil infiltration owing to the administration of an H(2)-blocker. CONCLUSIONS: There are two different pathological phenotypes of murine AIG, chronic gastritis and hypertrophic gastritis, in NTx AIG BALB/c mice. Furthermore, eosinophil infiltration and the Th2 immune response might play a key role in the phenotypic shift from chronic gastritis to hypertrophic gastritis in these mice.