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.

Frontal deficits and atrophy in a patient with familial encephalopathy with neuroserpin inclusion bodies detected by single-case voxel-based morphometry: a case report.

BACKGROUND: Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare genetic disorder characterized by progressive cognitive decline and myoclonic epilepsy, caused by pathogenic variants of SERPINI1. We reported a case of genetically confirmed FENIB with de novo H338R mutation in the SERPINI1, in which frontal deficits including inattention and disinhibition, and relevant atrophy in the vmPFC on brain MRI were observed in the early stage of the disease. CASE PRESENTATION: A 23-year-old Japanese man presented with progressive inattention and disinhibition over 4 years followed by myoclonic epilepsy. The whole-genome sequencing and filtering analysis showed de novo heterozygous H338R mutation in the SERPINI1, confirming the diagnosis of FENIB. Single-case voxel-based morphometry using brain magnetic resonance imaging obtained at the initial visit revealed focal gray matter volume loss in the ventromedial prefrontal cortices, which is presumed to be associated with inattention and disinhibition. CONCLUSION: Frontal deficits including inattention and disinhibition can be the presenting symptoms of patients with FENIB. Single-case voxel-based morphometry may be useful for detecting regional atrophy of the frontal lobe in FENIB. Detecting these abnormalities in the early stage of disease may be key findings for differentiating FENIB from other causes of progressive myoclonic epilepsy.

Influence of proficiency in conventional laparoscopic surgery in colorectal cancer on the introduction of robotic surgery.

PURPOSE: Although there have been many reports on learning curves for robotic surgery, it is unclear how surgeons' conventional laparoscopic surgical skills influence their ability in performing robotic surgery for colorectal cancer (CRC). The aim of this study was to determine the surgical outcomes of robotic surgery for CRC during the induction phase by skilled laparoscopic surgeons. METHODS: Surgical outcomes of consecutive CRC cases between January 2021 and March 2023 following the skilled phase of laparoscopic surgery and introductory phase of robotic surgery performed by three skilled laparoscopic surgeons were compared. RESULTS: Overall, 77 consecutive patients diagnosed with sigmoid colon or rectosigmoid cancer were analysed, including 50 in the laparoscopy group (LAP) and 27 in the robotic group (Ro). Patient characteristics, including age, sex, body mass index, and tumour progression, did not differ between the groups. The median operation time was 204 min in the robotic group and 170 min in the laparoscopic group (p < 0.001). Blood loss was significantly lower in the robotic group (p = 0.0059). The incidence of grade 2 or higher complications did not differ between the two groups (LAP, 10.0% vs. Ro, 7.4%, p = 1). In the robotic group, the time required for lymph node dissection had a greater impact on operative duration. CONCLUSION: Skills acquired from performing conventional laparoscopic surgery may contribute to the safe and reliable performance of robotic surgery for CRC. TRIAL REGISTRATION: UMIN000050923.

Noradrenergic Pathway to the Cerebellum: the Study Must Go On.

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.

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.

Novel approach toward minimally invasive surgery for mid-transverse colon cancer: 'moving the left colon' technique.

AIM: During surgery for mid-transverse colon cancer (MTC), surgeons often face the dilemma of whether to mobilize the hepatic or splenic flexure. There is no established optimal minimally invasive surgical procedure for MTC. METHODS: We present our novel minimally invasive surgical technique, called the 'moving the left colon' technique for MTC, along with a video demonstration. The procedure involves four main steps: (i) mobilization of the splenic flexure using a medial-to-lateral approach, (ii) dissection of lymph nodes around the middle colic artery from the left side of the superior mesenteric artery approach, (iii) separation of the pancreas and transverse mesocolon and (iv) 'moving the left colon' and performing an intracorporeal anastomosis. By mobilizing the splenic flexure, anatomical landmarks are revealed, which enables safer dissection. Combining this technique with intracorporeal anastomosis allows for a safe and easy anastomosis. RESULTS: Between April 2021 and January 2023, a single-skilled colorectal surgeon performed laparoscopic transverse colectomies using our new approach on three consecutive patients with MTC. The patients had a median age of 75 years (range 46-89 years). The median operative time was 194 min (range 193-228 min) and blood loss was 8 mL (range 0-20 mL). None of the patients experienced any perioperative complications and the median postoperative hospital stay was 6 days. CONCLUSION: We introduced a novel approach for laparoscopic surgery for MTC. This technique can be performed safely and may help standardize minimally invasive surgery for MTC.

Effects of the combination of atomoxetine and oxybutynin in Japanese patients with obstructive sleep apnoea: A randomized controlled crossover trial.

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.

Ultrasound-based radiomic analysis of the peripheral nerves for differentiation between CIDP and POEMS syndrome.

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.

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.

Frequency of FMR1 Premutation Alleles in Patients with Undiagnosed Cerebellar Ataxia and Multiple System Atrophy in the Japanese Population.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder caused by FMR1 premutation expansion of CGG repeats. FXTAS can be misdiagnosed with many neurodegenerative disorders manifesting with cerebellar ataxias owing to their overlapping clinical and radiological features. The frequency of the FMR1 premutation allele in Japan has not been fully determined. Herein, we aimed to determine the frequency of FMR1 premutation alleles in Japanese patients with undiagnosed cerebellar ataxia and multiple system atrophy, using repeat-primed PCR in 186 patients with adult onset of undiagnosed cerebellar ataxia and 668 patients with multiple system atrophy, to identify expanded CGG repeats as well as to detect AGG interruptions within the expanded alleles. The size of expansions was estimated using fragment length analysis of PCR products obtained by conventional PCR employing a pair of unique primers flanking the repeat sequence. We identified FMR1 premutation alleles in three male patients. One patient revealed 84 repeat units with one AGG interruption and another patient showed 103 repeat units. Both had presented with sporadic cerebellar ataxia, giving an estimated frequency of 3.7% among Japanese male patients with sporadic cerebellar ataxia with age at onset above 50 years. One patient with the clinical diagnosis of multiple system atrophy harbored 60 repeat units with four AGG interruptions. FMR1 intermediate alleles were observed in two males and one female among the multiple system atrophy patients. We found that genetic tests for FMR1 premutation should be considered in Japanese male patients with cerebellar ataxia with the age at onset above 50 years.

Nerve Hypertrophy and Altered Diffusion in Anti-Myelin-Associated Glycoprotein Neuropathy Detected by Brachial Plexus Magnetic Resonance Neurography.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sleep-related hypoventilation and hypercapnia in multiple system atrophy detected by polysomnography with transcutaneous carbon dioxide monitoring.

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.

Magnetic resonance T1w/T2w ratio in the middle cerebellar peduncle might be a sensitive biomarker for multiple system atrophy.

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.

Cerebral large artery stenosis and occlusion in POEMS syndrome.

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.

Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case.

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.

Cognitive Impairment in Multiple System Atrophy Is Related to White Matter Damage Detected by the T1-Weighted/T2-Weighted Ratio.

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.

Chorea-acanthocytosis: Time-dependent changes of symptoms and imaging findings.

BACKGROUND AND PURPOSE: Chorea-acanthocytosis, a rare neurodegenerative disease, affects both the striatum and the medial temporal lobe which may cause involuntary movements and epilepsy, respectively. We examined the imaging changes of the hippocampus/amygdala and the striatum as well as clinical symptoms. MATERIALS AND METHODS: We retrospectively reviewed 29 MRI and 13 SPECT studies and the clinical findings of seven genetically confirmed chorea-acanthocytosis patients. We evaluated the time-dependent imaging changes of the hippocampus/amygdala and striatum and examined the relationships among these images and symptoms. RESULTS: The initial symptom was epilepsy in four patients and involuntary movements in three patients. These symptoms were eventually noted in five and all seven patients, respectively. On MRI, most patients showed striatum atrophy before a hippocampus/amygdala abnormality emerged, but one patient showed a hippocampus/amygdala abnormality before striatum atrophy. Abnormal MRI findings of hippocampus/amygdala were noted in five patients and atrophy of striatum in all seven patients. SPECT demonstrated hypoperfusion of hippocampus/amygdala in three patients and that of striatum in all five available patients. Four patients demonstrated hypoperfusion of striatum earlier than that of hippocampus/amygdala and one patient showed hypoperfusion of both simultaneously. Many imaging abnormal lesions were accompanied by their corresponding symptoms, but not always so. CONCLUSION: Striatum abnormalities were the initial imaging findings in many chorea-acanthocytosis patients, but epilepsy or hippocampus/amygdala imaging abnormalities may be the only findings at the early stage. It is important to understand the detailed clinical and imaging time courses for the diagnosis of chorea-acanthocytosis.

Vertical pons hyperintensity and hot cross bun sign in cerebellar-type multiple system atrophy and spinocerebellar ataxia type 3.

BACKGROUND: The "hot cross bun" (HCB) sign, a cruciform hyperintensity in the pons on magnetic resonance imaging (MRI), has gradually been identified as a typical finding in multiple system atrophy, cerebellar-type (MSA-C). Few reports have evaluated the sensitivity of an HCB, including a cruciform hyperintensity and vertical line in the pons, which precedes a cruciform hyperintensity, in the early stages of MSA-C. Moreover, the difference in frequency and timing of appearance of an HCB between MSA-C and spinocerebellar ataxia type 3 (SCA3) has not been fully investigated. METHODS: This study investigated the time at which an HCB and orthostatic hypotension (OH) appeared in 41 patients with MSA-C, based on brain MRI and head-up tilt test. The MRI findings were compared with those of 26 patients with SCA3. The pontine signal findings on T2-weighted MRI were graded as 0 (no change), 1 (a vertical T2 high-intensity line), or 2 (a cruciform T2 high-intensity line), with grades 1 or 2 considered as an HCB. OH 30/15 was defined as a decrease in systolic blood pressure of > 30 mmHg or diastolic blood pressure of > 15 mmHg. RESULTS: Among the 24 patients with MSA-C within 2 years from the onset of motor symptoms, an HCB was detected in 91.7%, whereas OH 30/15 was present in 60.0%. Among the 36 patients with MSA-C within 3 years from the onset of motor symptoms, a grade 2 HCB was detected in 66.7% of those with MSA-C but in none of those with SCA-3. CONCLUSIONS: HCB is a highly sensitive finding for MSA-C, even in the early stages of the disease. A grade 2 HCB in the early stage is an extremely specific finding for differentiating MSA-C from SCA-3.

Different Patterns of Gray Matter Volume Reduction in Early-onset and Late-onset Alzheimer Disease.

BACKGROUND: Individuals with early-onset Alzheimer disease (EOAD) differ from those with late-onset Alzheimer disease (LOAD) not only in genetics and age at onset but also in their clinical symptoms. OBJECTIVE: To differentiate the neuropathological and neurocognitive features of EOAD and LOAD by comparing the pattern of regional gray matter volume (GMV) reduction and its symptomatic correlates. METHOD: Three-dimensional T1-weighted MRIs and Mini-Mental State Examination (MMSE) scores were obtained from 12 individuals with EOAD, 65 with LOAD, and 49 healthy controls (HC). Regional GMV reduction between the three groups was assessed using voxel-based morphometry. Multiple regression analyses were conducted with MMSE total score as an independent variable. RESULTS: Compared to the HC, both AD groups showed a significant GMV reduction in the bilateral hippocampus and the left temporoparietal junction; in addition, the LOAD group showed one in the bilateral anterior temporal lobes. Multiple regression analyses revealed a positive correlation between MMSE total score and GMV in the left anterior temporal lobe in both AD groups; that is, lower scores were associated with reduced GMV. Interestingly, a positive correlation in hippocampal GMV was revealed only in the LOAD group. CONCLUSION: MMSE total score is associated with the anterior temporal lobe volume in individuals with AD. Hippocampal volume and its relationship with MMSE total score are associated with LOAD pathophysiology but not EOAD pathophysiology. The hippocampal volume reduction and low MMSE scores are hallmarks of LOAD but are less specific to EOAD, which may cause a delay in diagnosis.

[A Case of Metastatic Small Intestinal Tumor Diagnosed with Intestinal Obstruction].

A 76-year-old man with a past history of liver transplantation because of liver cirrhosis visited a hospital in October 2018 because of vomiting and abdominal pain. Although the patient underwent conservative medical treatment, no improvement of the symptoms was observed, and he received consultation at our hospital. After thorough examination, and because of the policy of inpatient treatment after the diagnosis of adhesion ileus obstruction post liver transplantation surgery, intestinal decompression was performed using an ileus tube. However, there was no improvement in the symptoms even after inserting the ileus tube, and intestinal obstruction was diagnosed in November 2018. During the preoperative examination, a tumorous shadow was found in the right lung, although it became a policy of scrutiny after improvement of the bowel obstruction. During the laparotomy, a macroscopic tumor exposed on the serosal surface was observed on the anal side at 120 cm from the Treitz ligament, and this site was considered to be the blocking origin. Partial resection of the small intestine including the blockage site was performed. The pathological result revealed the diagnosis of adenosquamous carcinoma. Furthermore, immunostaining was CK7 positive, CK20 negative, TTF-1 negative, and Napsin negative, suggesting the possibility of a metastatic tumor derived from lung cancer. The postoperative course was uneventful, and the patient was discharged on postoperative day 9. On day 30 after surgery, the left pleural effusion increased and pleural effusion cytology revealed a diagnosis of primary lung adenocarcinoma Stage Ⅳ. Considering the patient's PS, it became a best supportive care(BSC)policy after consultation with the family, and it ended on postoperative day 70. Here, we report about a case diagnosed with metastatic small bowel cancer and intestinal obstruction and conduct a literature review.