杉山 淳比古

Abstract 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.

We report the case of a woman in her 40s who presented with sensory disturbances in all 4 limbs and left facial palsy. MRI revealed asymmetric enlargement of the dorsal root ganglia, which was enhanced by gadolinium-a chest CT scan identified enlarged supraclavicular, mediastinal, and hilar lymph nodes. A biopsy of a hilar lymph node showed noncaseating epithelioid granulomas, confirming a sarcoidosis diagnosis. Prednisolone treatment led to symptomatic improvements. In sarcoidosis of the peripheral nervous system, there might be observable enlargement of the dorsal root ganglion alongside enhanced gadolinium contrast. Obtaining a biopsy from the dorsal root ganglion poses challenges, and radiologists should be mindful of this specific imaging characteristic.

Multiple system atrophy with predominant parkinsonism (MSA-P) can hardly be distinguished from Parkinson’s disease (PD) clinically in the early stages. This study investigated whether a standardized T1-weighted/T2-weighted ratio (sT1w/T2w ratio) can effectively detect degenerative changes in the middle cerebellar peduncle (MCP) associated with MSA-P and PD and evaluated its potential to distinguish between these two diseases. We included 35 patients with MSA-P, 32 patients with PD, and 17 controls. T1w and T2w scans were acquired using a 1.5-T MR system. The MCP sT1w/T2w ratio was analyzed via SPM12 using a region-of-interest approach in a normalized space. The diagnostic performance of the MCP sT1w/T2w ratio was compared between the MSA-P, PD, and controls. Patients with MSA-P had significantly lower MCP sT1w/T2w ratios than patients with PD and controls. Furthermore, MCP sT1w/T2w ratios were lower in patients with PD than in the controls. The MCP sT1w/T2w ratio showed excellent or good accuracy for differentiating MSA-P or PD from the control (area under the curve (AUC) = 0.919 and 0.814, respectively) and substantial power for differentiating MSA-P from PD (AUC = 0.724). Therefore, the MCP sT1w/T2w ratio is sensitive in detecting degenerative changes in the MCP associated with MSA-P and PD and is useful in distinguishing MSA-P from PD.

Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank. Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred. Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank. Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches.

The most common genetic Creutzfeldt-Jakob disease (gCJD) in Japan is caused by a point mutation in which isoleucine replaces valine at codon 180 of the prion protein (PrP) gene (V180I gCJD). Evidence suggests that cerebral cortex swelling, which appears as abnormal hyperintensities on diffusion-weighted imaging (DWI), is a characteristic magnetic resonance imaging (MRI) finding of V180I gCJD. However, no study has directly compared the MRI findings between V180I gCJD and sporadic CJD (sCJD). The current study, therefore, aims to clarify the imaging features of V180I gCJD, which would lead to prompt genetic counselling and analysis of the PrP gene, particularly focusing on cerebral cortex swelling. We included 35 patients with sCJD (n = 23) or V180I gCJD (n = 12). Cerebral cortex swelling on T2-weighted imaging (T2WI) or fluid-attenuated inversion recovery (FLAIR) wherein abnormal cortical hyperintensities were observed on DWI, and the distribution of grey matter hyperintensities on DWI were visually evaluated. V180I gCJD patients had significantly more cerebral cortex swelling (100% vs. 13.0%, p < 0.001), an overall correct classification of 91.4%, and parahippocampal gyrus hyperintensities on DWI (100% vs. 39.1%, q = 0.019) than sCJD patients. Cerebral cortical hyperintensities on DWI with swelling on T2WI or FLAIR are characteristic imaging findings of V180I gCJD and are useful for differentiating it from sCJD.

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.

Background Demyelinating peripheral neuropathy is characteristic of both polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). We hypothesized that the different pathogeneses underlying these entities would affect the sonographic imaging features. Purpose To investigate whether ultrasound (US)-based radiomic analysis could extract features to describe the differences between CIDP and POEMS syndrome. Material and Methods In this retrospective study, we evaluated nerve US images from 26 with typical CIDP and 34 patients with POEMS syndrome. Cross-sectional area (CSA) and echogenicity of the median and ulnar nerves were evaluated in each US image of the wrist, forearm, elbow, and mid-arm. Radiomic analysis was performed on these US images. All radiomic features were examined using receiver operating characteristic analysis. Optimal features were selected using a three-step feature selection method and were inputted into XGBoost to build predictive machine-learning models. Results The CSAs were more enlarged in patients with CIDP than in those with POEMS syndrome without significant differences, except for that of the ulnar nerve at the wrist. Nerve echogenicity was significantly more heterogeneous in patients with CIDP than in those with POEMS syndrome. The radiomic analysis yielded four features with the highest area under the curve (AUC) value of 0.83. The machine-learning model showed an AUC of 0.90. Conclusion US-based radiomic analysis has high AUC values in differentiating POEM syndrome from CIDP. Machine-learning algorithms further improved the discriminative ability.

背景:デュシェンヌ/ベッカー型筋ジストロフィー(DMD/BMD)はともにX染色体上のジストロフィン遺伝子変異を原因とする遺伝性疾患だが,DMDはフレームシフト/ナンセンス変異により若年発症し進行が速い。出生前/着床前診断の対象となりうるためBMDとの鑑別は重要である。症例:11歳女児,ジストロフィン遺伝子のサザンブロット解析でin-frame欠失を認め,BMD保因者であることが示唆された。29歳時,挙児希望にて周産期遺伝カウンセリング目的に来院。MLPA再解析でout-of-frame欠失を認め,DMD保因者であることが示唆された。考察:遺伝子解析方法により欠失領域の判定が異なる結果となった症例を経験した。解析方法の進歩によって,過去の検査結果や解釈が変化することがある。結論:欠失領域の判定は筋ジストロフィーのタイプに直接関係する。周産期遺伝カウンセリングにおいては注意が必要である。(著者抄録)

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with various neurological manifestations, including tremor. Here, we report a case involving a 68-year-old man with an 8-year history of tremor in his right arm. Subsequently, examination revealed that the patient was suffering from a low-frequency, high-amplitude, and posture-induced proximal arm tremor elicited by sustained arm abduction with flexed elbows (wing-beating tremor), which was partially improved by zonisamide treatment. Abnormal expansion of GGC repeats in the NOTCH2NLC gene confirmed the diagnosis of NIID. This case highlights the fact that unilateral wing-beating tremor can be a manifestation of NIID. Zonisamide may be effective for controlling tremors associated with NIID.

This study aimed to explore morphological changes of hippocampal subfields in patients with multiple system atrophy (MSA) with and without cognitive impairment using FreeSurfer-automated segmentation of hippocampal subfield techniques and their relationship with cognitive function. We enrolled 75 patients with MSA classified as cognitively impaired MSA (MSA-CI, n = 40) and cognitively preserved MSA (MSA-CP, n = 35), as well as 68 healthy controls. All participants underwent three-dimensional volume T1-weighted magnetic resonance imaging. The hippocampal subfield volume was measured using FreeSurfer version 7.2 and compared among groups. Regression analyses were performed between the hippocampal subfield volumes and cognitive variables. Compared with healthy controls, the volume of the right cornu ammonis (CA) 2/3 was significantly lower in the MSA-CI group (P=0.029) and that of the left fimbria was significantly higher in the MSA-CP group (P=0.046). Results of linear regression analysis showed that the right CA2/3 volume was significantly correlated with the Frontal Assessment Battery score in patients with MSA (adjusted R 2 = 0.282, β = 0.227, and P=0.041). The hippocampal subfield volume decreased in patients with MSA-CI, even at the early disease stages. Specific structural changes in the hippocampus might be associated with cognitive deficits in MSA.

Abstract We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed. We first sequenced the 12 molecularly diagnosed patients and accurately confirmed expanded repeats in all with uniform depth of coverage across the loci. Next, we applied our method and a conventional method to 10 molecularly undiagnosed patients. Our method corrected inaccurate diagnoses of two patients by the conventional method. Our method is superior to conventional diagnostic methods in terms of speed, accuracy, and comprehensiveness.

OBJECTIVES: Currently, no established biomarkers exist for presymptomatic sporadic Creutzfeldt-Jakob disease (sCJD). The purpose of this study was to raise awareness about sCJD cases showing abnormalities on brain MRI diffusion-weighted imaging (DWI) before symptom onset and demonstrate temporal changes in DWI abnormalities during the preclinical period. METHODS: We described the clinical presentation including the results of MRI-performed multiple times in the preclinical period-and the diagnostic workup of a middle-aged man with sCJD. RESULTS: MRI of the brain performed 27 months before symptom onset revealed an extremely localized lesion on DWI in the right occipital cortex. Follow-up MRI scans showed propagation of DWI abnormalities along the cortices without the appearance of neurologic symptoms/signs. After symptom onset, the patient's neuropsychiatric condition rapidly deteriorated. Elevated total tau protein levels and positive 14-3-3 protein were observed in the CSF, and periodic synchronous discharges using electroencephalography resulted in the diagnosis of sCJD. DISCUSSION: CJD should be considered in differential diagnoses when localized DWI signal abnormalities propagate along the cortices over time, even in the absence of typical CJD symptoms. DWI signal abnormalities on brain MRI scans may be highly sensitive diagnostic markers for CJD, even in the preclinical stage.

BACKGROUND AND OBJECTIVE: The possibility of combination therapy with atomoxetine (ATO) and oxybutynin (OXY) has been suggested for obstructive sleep apnoea (OSA). However, the effectiveness of this treatment remains uninvestigated in Japanese OSA patients. Therefore, we performed a randomized, crossover, phase II, single-centre prospective trial to examine the effects of ATO-OXY therapy in Japanese OSA patients. METHODS: In total, 17 OSA patients participated in this study. The effects of one night of 80-mg ATO plus 5-mg OXY administration were compared with those of no medication administered before sleep. The primary and secondary outcomes comprised the apnoea-hypopnoea index (AHI) and nadir SpO2 , SpO2 drop time and sleep architecture, respectively. The safety endpoints included drug side effects and adverse events. RESULTS: The values of AHI, nadir SpO2 , 3% oxygen desaturation index (ODI), 4% ODI, and SpO2 drop time of <90% did not significantly differ between patients receiving ATO-OXY administration and no medication. Sleep architecture exhibited a significant change: ATO-OXY increased sleep stage N1 (p < 0.0001) and decreased stage N2 (p = 0.03), rapid eye movement (p < 0.0001) and sleep efficiency (p = 0.02). However, the subanalysis demonstrated an obvious decrease in AHI in five responder patients. Total sleep time and basal sleep efficiency tended to be lower in the responders compared with nonresponders (p = 0.065). No patients experienced severe adverse events or side effects. CONCLUSION: Overall, ATO-OXY therapy does not reduce AHI in Japanese OSA patients, although AHI was decreased in a proportion of patients. Future studies for identifying treatment response group characteristics are warranted.

OBJECTIVE: This study aimed to clarify the relationship between progressive medial temporal atrophy and onset subtype in patients with amyotrophic lateral sclerosis (ALS). METHODS: Medial temporal atrophy, ALS functional rating scale (ALSFRS), and cognitive function were assessed in 119 patients who were grouped into three ALS subtypes: bulbar, upper limb, and lower limb onset. Medial temporal atrophy, represented by a Z-score, was determined using an analysis software of magnetic resonance images known as the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Among 119 patients, 60 underwent follow-up VSRAD, ALSFRS, and cognitive testing. The sequential data were compared among onset subtypes. Furthermore, TDP-43 pathology was assessed in 20 autopsied patients (including seven who underwent VSRAD before death) to examine the relationships among medial temporal atrophy, onset subtypes, and severity of the hippocampal TDP-43 pathology. RESULTS: Multiple regression analysis revealed that the Z-score at baseline was associated with the age of onset and duration of illness. A high Z-score at baseline and the bulbar/upper limb subtypes affected the progression rate of Z-score. Pathological examination revealed increased hippocampal TDP-43 pathology score associated with bulbar and upper limb subtypes. Moreover, the Z-score before death correlated with the hippocampal TDP-43 pathology score. CONCLUSION: Medial temporal atrophy in ALS is associated with bulbar and upper limb onset subtypes. This progression may be related to the extent of TDP-43 pathology.

In 1967, Andén, Fuxe, and Ungerstedt demonstrated the presence of monoamine-containing fibers in the rat cerebellum. Over the past 50 years, this finding has provided clinical relevance of the noradrenergic system to the cerebellum. Cerebellar dysfunction and noradrenergic system may relate to tremor in Parkinson disease and essential tremor, motor learning, and the vestibulo-ocular reflex in spinocerebellar ataxias. Cognition and emotion may also be linked to the cerebellar noradrenergic system, in relation to the symptoms of Alzheimer disease, dementia with Lewy bodies, and attention-deficit/hyperactivity disorder. Despite recent technological advances in neuroimaging for evaluating the noradrenergic system, we need more evidence to understand the precise pathophysiological relationship between the cerebellum and the noradrenergic system and its clinical implications.

We describe the case of a 60-year-old man with a 16-year history of gait imbalance and 15-year history of forgetfulness. The insidious onset and slow progression suggested that the disease was degenerative. Neurologic examination revealed cerebellar ataxia, chorea, and mild cognitive impairment. Brain magnetic resonance imaging revealed prominent cerebellum atrophy and diffuse atrophy in the brainstem and cerebrum. Based on neurologic manifestations, an additional patient interview and skin examination were conducted. Photosensitivity and freckling in exposed areas, which the patient did not recognize as disease symptoms, were observed. Based on acute and chronic photosensitivity and DNA repair test results, a final diagnosis was made. In patients with cerebellar ataxia, chorea, and cognitive dysfunction of unknown etiology, clinicians should explore patient history of photosensitivity and carefully examine the skin.

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.

We herein report a case of genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein (PrP) gene diagnosed at a preserved cognitive function stage. Although neuropsychological tests revealed normal cognitive functions, increased signal intensity in the cerebral cortices with swelling on diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI) prompted genetic testing for the PrP gene. This case suggests that cortical hyperintensity on DWI with swelling may be a useful finding of brain MRI for the diagnosis of V180I genetic CJD even at an extremely early stage, such as at the preserved cognitive function stage.

Myoclonus and ataxia, with or without opsoclonus, have recently been recognized as a central nervous system syndrome associated with coronavirus disease-2019 (COVID-19). A 52-year-old Japanese man developed myoclonus and ataxia 16 days after the onset of COVID-19. Brain single-photon emission computed tomography (SPECT) revealed hyperperfusion in the cerebellum and hypoperfusion in the cerebral cortices with frontal predominance during the acute stage, which improved over two months. This study indicates that brain perfusion SPECT can be effective in detecting functional alterations in COVID-19-related myoclonus and ataxia.

PURPOSE: We aimed to evaluate sleep-related hypoventilation in multiple system atrophy (MSA) using polysomnography (PSG) with transcutaneous partial pressure of carbon dioxide (PtcCO2) monitoring. METHODS: This prospective study included 34 patients with MSA. Motor and autonomic function, neuropsychological tests, PSG with PtcCO2 monitoring, and pulmonary function tests were performed. Sleep-related hypoventilation disorder (SRHD) was defined according to the International Classification of Sleep Disorders, third edition. RESULTS: Nine (27%) of the 34 patients met the diagnostic criteria of SRHD. Twenty-nine (85%) patients had sleep-related breathing disorders based on an Apnea-Hypopnea Index of ≥ 5/h. The patients with MSA and SRHD had a higher arousal index (p = 0.017) and obstructive apnea index (p = 0.041) than those without SRHD. There was no difference in the daytime partial pressure of carbon dioxide in arterial blood or respiratory function between MSA patients with and without SRHD. CONCLUSION: Sleep-related hypoventilation may occur in patients with MSA even with a normal daytime partial pressure of carbon dioxide. This can be noninvasively detected by PSG with PtcCO2 monitoring. SRBD and sleep-related hypoventilation are common among patients with MSA, and clinicians should take this into consideration while evaluating and treating this population.

Frontotemporal brain sagging syndrome (FBSS) is a progressive disorder characterized by symptoms similar to the behavioral variant of frontotemporal dementia (FTD), with a sagging appearance of the brain on imaging similar to that observed in spontaneous intracranial hypotension (SIH). The onset of behavioral and cognitive symptoms of FBSS is insidious and progressive, similar to those of FTD. Here, we report a case involving a 53-year-old man with progressive hypersomnolence, apathy, forgetfulness, and personality changes but without headache or auditory symptoms. The combination of frontotemporal dysfunction, hypersomnolence, and the appearance of a sagging brain on magnetic resonance imaging suggested a diagnosis of FBSS. Although a definite site of cerebrospinal fluid leakage could not be identified in our case, clinical symptoms and imaging findings were improved after an epidural blood patch. Considering FBSS as a differential diagnosis of FTD is important even in the absence of typical SIH symptoms, such as headache or auditory symptoms.

BACKGROUND: The standardized T1-weighted/T2-weighted (sT1w/T2w) ratio for the middle cerebellar peduncle (MCP) has been reported to be sensitive for detecting degenerative changes in the cerebellar subtype of multiple system atrophy (MSA-C), even in the early stages. We aimed to investigate the diagnostic value of the MCP sT1w/T2w ratio for differentiating between MSA-C and spinocerebellar ataxia (SCA). METHODS: We included 32 MSA-C, 8 SCA type 3 (SCA3), 16 SCA type 6 (SCA6) patients, and 17 controls, and the MCP sT1w/T2w ratio was analyzed using a region-of-interest approach. The diagnostic performance of the MCP sT1w/T2w ratio in discriminating among MSA-C, SCA3, and SCA6 was assessed and compared with diagnosis based on visual interpretation of MCP hyperintensities and the "hot cross bun" (HCB) sign. RESULTS: MCP sT1w/T2w ratio values were markedly lower in patients with MSA-C than in those with SCA3, those with SCA6, and controls (p < 0.001). The MCP sT1w/T2w ratio showed high diagnostic accuracy for distinguishing MSA-C from SCA3 (area under curve = 0.934), SCA6 (area under curve = 0.965), and controls (area under curve = 0.980). The diagnostic accuracy of the MCP sT1w/T2w ratio for differentiating MSA-C from SCA3 or SCA6 (90.0% for MSA-C vs. SCA3, and 91.7% for MSA-C vs. SCA6) was comparable to or superior than that of visual interpretation of MCP hyperintensities (80.0-87.5% in MSA-C vs. SCA3 and 87.6-97.9% in MSA-C vs. SCA6) or the HCB sign (72.5-80.0% in MSA-C vs. SCA3 and 77.1-93.8% in MSA-C vs. SCA6). CONCLUSIONS: The MCP sT1w/T2w ratio might be a sensitive imaging-based marker for detecting MSA-C-related changes and differentiating MSA-C from SCA3 or SCA6.

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; This study assessed the morphological changes and diffusion tensor imaging (DTI)-derived parameters of the brachial plexus using magnetic resonance neurography (MRN) in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Eight patients with anti-MAG neuropathy underwent MRN of the brachial plexus with 3-dimensional (3D) short tau inversion recovery (STIR) and DTI sequences. Two neuroradiologists and a neurologist qualitatively assessed nerve hypertrophy on 3D STIR MRN. The cross-sectional area (CSA) of the nerve roots was measured. Quantitative analyses of fractional anisotropy (FA) and axial, radial, and mean diffusivity (AD, RD, and MD) were obtained after postprocessing on DTI and manual segmentation. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; There was nerve hypertrophy in 37.5% of the patients with anti-MAG neuropathy. All patients with anti-MAG neuropathy with nerve hypertrophy were refractory to rituximab therapy. The CSA of the nerve roots was inversely correlated with FA and positively correlated with MD and RD. FA decreased in the nerve roots and inversely correlated with disease duration. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Nerve hypertrophy appears in the proximal portion of peripheral nerves, such as the brachial plexus, in patients with anti-MAG neuropathy. Altered diffusion in the nerve roots might be associated with the loss of myelin integrity due to the demyelination process in anti-MAG neuropathy.

INTRODUCTION: This study aimed to use a novel MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, to assess damage of the white matter and gray matter in multiple system atrophy (MSA). Furthermore, this study investigated whether the sT1w/T2w ratio was associated with cognitive impairment in MSA. METHODS: The white matter and gray matter sT1w/T2w ratio of 37 MSA patients and 19 healthy controls were measured. Correlation analyses were used to evaluate the relationship between sT1w/T2w ratio values and clinical variables, and a multivariate analysis was used to identify independent factors associated with cognitive impairment in MSA. RESULTS: MSA patients showed a higher white matter sT1w/T2w ratio value than controls (p < 0.001), and the white matter sT1w/T2w ratio value was significantly correlated with the International Cooperative Ataxia Rating Scale score (r = 0.377, p = 0.021) and the Addenbrooke's cognitive examination III score (r = -0.438, p = 0.007). Cognitively impaired MSA patients had a significantly higher white matter sT1w/T2w ratio value than cognitively preserved MSA patients (p = 0.010), and the multiple logistic regression analysis revealed that the median white matter sT1w/T2w ratio value was independently associated with cognitive impairment in MSA. CONCLUSION: The sT1w/T2w ratio is sensitive to degenerative changes in the white matter that is associated with cognitive ability in MSA patients.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. CASE PRESENTATION: A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. CONCLUSIONS: We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

BACKGROUND: This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. METHODS: We reviewed results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) in 61 patients with POEMS syndrome seen between 2010 and 2017. Stenosis or occlusion was assessed in the initial MRA/CTA. Multivariate analysis was used to identify risk factors for artery stenosis/occlusion. In an autopsy case, pathologic examination was conducted of the occluded middle cerebral arteries. RESULTS: Stenosis (> 50 %) or occlusion of the major cerebral arteries was found in 29 (47.5 %) patients on the initial MRA/CTA. The internal carotid artery was involved most frequently (32.8 %), followed by the anterior (21.3 %) and middle (16.4 %) cerebral arteries. The basilar (1.3 %) and vertebral (3.6 %) arteries were rarely affected. Cerebral infarction developed in eight (13.1 %) patients. The serum vascular endothelial growth factor (VEGF) level was an independent predictor for stenosis/occlusion (odds ratio, 1.228; 95 % confidence interval, 1.042-1.447; P = 0.014). An autopsy study showed occluded middle cerebral arteries by fibrous and myxomatous thickening of intima with splitting of the internal elastic lamina. Follow-up MRA in 23 patients showed improved, worsened, and unchanged stenosis in 20.7 %, 8.7 %, and 69.6 %, respectively. CONCLUSIONS: Cerebral large-vessel stenosis or occlusion is frequently seen in approximately half of patients with POEMS syndrome. Vasculopathy was related to serum VEGF levels and thereby disease activity. Assessment of cerebral vessels is recommended in these patients to improve management.

OBJECTIVE: We aimed to investigate the use of a myelin-sensitive MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, for detecting early changes in the middle cerebellar peduncle (MCP) in cerebellar subtype multiple system atrophy (MSA-C) patients. METHODS: We included 28 MSA-C patients, including a subset of 17 MSA-C patients within 2 years of disease onset (early MSA-C), and 28 matched healthy controls. T1w and T2w scans were acquired using a 3-T MR system. The sT1w/T2w ratio in MCP was analyzed using SPM12 by utilizing a region-of-interest approach in normalized space. The diagnostic performance of the MCP sT1w/T2w ratio in discriminating MSA-C and the subgroup of early MSA-C from the matched controls was assessed. Correlation analyses were performed to evaluate the relationship between the MCP sT1w/T2w ratio and other clinical parameters including the International Cooperative Ataxia Scale (ICARS) score for quantifying cerebellar ataxia. RESULTS: Compared to controls, the sT1w/T2w ratio in the MCP was markedly lower in all (p < 0.001) MSA-C patients and 17 early (p < 0.001) MSA-C patients. The MCP sT1w/T2w ratio had high sensitivity (96%) and specificity (100%) to distinguish MSA-C from controls (area under the curve = 0.99), even for the early MSA-C group (area under the curve = 0.99; sensitivity = 94%, specificity = 100%). The MCP sT1w/T2w ratio correlated with the ICARS score in early MSA-C. CONCLUSIONS: The sT1w/T2w ratio can detect MSA-C-related changes in the MCP, even in the early stages of the disorder, and could be a sensitive biomarker for MSA-C. KEY POINTS: • The sT1w/T2w ratio can detect MSA-C-related changes in the middle cerebellar peduncle, even in the early stages of the disorder. • The middle cerebellar peduncle sT1w/T2w ratio correlated with a cerebellar ataxia score in early MSA-C patients.

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.