Akitoshi Takeda

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma

Among 249 patients with teratoma‐associated encephalitis, 211 had N‐methyl‐D‐aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody‐positive patients rarely developed prominent brainstem–cerebellar symptoms, 22 (58%) antibody‐negative patients developed a brainstem–cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12–41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem–cerebellar syndrome. ANN NEUROL 2014;75:435–441

Facial emotion recognition and cerebral white matter lesions in myotonic dystrophy type 1

In order to investigate the cognitive and neurological bases of social cognitive impairment in myotonic dystrophy type 1 (DM1), we examined the facial expression recognition abilities and the cerebral lesions in a group of DM 1 (5 men, 4 women). We measured sensitivity to facial emotions and compared the findings with magnetic resonance image (MRI) findings evaluated using a semi-quantitative method. The DM1 patients showed lower sensitivity to disgusted and angry faces as compared to the healthy controls. The assessment of brain lesions revealed that more severe lesions occurred in the frontal, temporal, and insular white matters. Sensitivity to the emotion of disgust was negatively correlated with temporal lesions, and sensitivity to anger negatively correlated with frontal, temporal, and insular lesions. The results of this study indicate an association between lesions in the frontal, temporal, and insular subcortices and decreased emotional sensitivity to disgust and anger in DM1 patients. These areas are thought to play an important role in emotional processing in the normal brain. Our results suggest that social cognitive impairment in DM1 patients is attributable to impaired emotional processing linked to white matter lesions.

Lowered sensitivity to facial emotions in myotonic dystrophy type 1.

BACKGROUND It has been observed that patients with myotonic dystrophy type 1 (DM1) exhibit social-cognitive impairment. However, the cognitive and neurological bases of the social-cognitive impairment in DM1 have not been adequately investigated. METHODS We studied cognitive deficits and impairment in facial expression recognition in two DM1 patients (one man and one woman). We measured the sensitivity of these patients to basic emotions and compared the results with those from magnetic resonance imaging and single photon emission computed tomography. RESULTS The DM1 patients showed lower sensitivity to fearful, disgusted, and angry faces than did the healthy controls. They also had lesions in the anterior temporal white matter, the amygdala, and the insular and orbitofrontal cortices. CONCLUSION The results of this study revealed that the DM1 patients had subcortical lesions in the anterior temporal areas, including the amygdala and the insular and orbitofrontal cortices. The limbic system, which includes these areas of the brain, plays an important role in emotional processing. Hence, the social-cognitive impairment in DM1 patients could be associated with a decreased sensitivity to facial expressions owing to lesions in the limbic system.

A case of anti-N-methyl-D-aspartate receptor encephalitis with multiple sclerosis-like demyelinated lesions

OBJECTIVE To describe an unusual case of a male patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis who presented with multiple white matter lesions. Brain biopsy of the patient was performed, and follow-up evaluation of the cerebrospinal fluid (CSF) NMDAR antibody titer was implemented. DESIGN Case report. SETTING University hospital. PATIENT A 35-year-old man with anti-NMDAR encephalitis initially presented with fever and psychiatric symptoms. After an initial attack of anti-NMDAR encephalitis, 2 atypical relapses occurred, which presented with myelitis and multifocal white matter lesions; the lesions were open-ring-shaped and partially enhanced. INTERVENTION Analysis of the brain biopsy specimen revealed the presence of demyelinated lesions with discrete borders. Subsequent intravenous methylprednisolone therapy resulted in improvement in the brain lesions. Prednisolone and cyclophosphamide were orally administered thereafter. Clinical progression of the disease paralleled observed changes in the CSF NMDAR antibody titer. CONCLUSION The demyelinated lesions observed in this case were similar to lesions found in multiple sclerosis. On the basis of our finding that the clinical progression of the disease and the associated symptoms paralleled changes in the CSF NMDAR antibody titer, we speculate that the lesions formed as a result of anti-NMDAR encephalitis.

Diffusion‐weighted imaging thermometry in multiple sclerosis

To prospectively investigate brain temperature using MR diffusion‐weighted imaging thermometry in multiple sclerosis (MS) patients and age‐matched healthy controls, to examine comparisons of brain temperature between MS patients and healthy volunteers, and to examine correlations between brain temperature and disease duration and between brain temperature and Expanded Disability Status Scale (EDSS) in MS patients.

Attention deficits in Japanese multiple sclerosis patients with minor brain lesion loads

Background To investigate whether Japanese multiple sclerosis (MS) patients with minor brain lesion loads have attention deficits and brain atrophy, and to correlate their circumstance. Method Twenty-one Japanese patients with relapsing-remitting MS were included in this study. Attention deficits were evaluated using Clinical Assessment for Attention (CAT) standardized according to age groups. Lesion load in the brain was assessed by tallying the total volume of plaques visible on brain magnetic resonance imaging (MRI). The width of the third ventricle and the bicaudate ratio were measured. Results The completion time for the visual cancellation tasks and/or the reaction times for the continuous performance test were prolonged in 14 patients (66.7%). The accuracy of responses was preserved throughout the CAT. Deviation from the normal value was not exaggerated based on the increasing difficulty of the task. The total volume of plaques on brain MRI was small. The width of the third ventricle was significantly increased in patients with MS when compared to controls, but was not correlated with the low performance on the CAT. Conclusions Japanese MS patients with minor brain lesion loads frequently had attention deficits characterized by slowness of automatic information processing, but controlled processing that requires working memory demands was spared.

Cerebral blood flow abnormality in clinically diagnosed Alzheimer's disease patients with or without amyloid β accumulation on positron emission tomography

The detection of amyloid β accumulation might be useful in confirming the diagnosis of Alzheimers disease in clinically suspected cases. However, confirmation of the disease by a positron emission tomography scan is not always available.

An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex: Globular glial tauopathy

Globular glial tauopathy (GGT) is a 4‐repeat (4R) tauopathy in which 4R tau accumulates to form globular glial inclusions (GGIs), predominantly in oligodendroglia. To date, little has been reported on iron deposits in patients with GGT. We report a case of GGT with iron deposits in a 78‐year‐old woman presenting with an 8‐year history of slowly progressing limb weakness and cognitive decline. Susceptibility‐weighted imaging revealed a low signal intensity in the right precentral gyrus, suggesting iron deposition. A clinical diagnosis of motor neuron disease with dementia was made 4 years after onset. At autopsy, gross pathological findings showed atrophy of the frontal and temporal lobes. A localized area of the precentral gyrus corresponding to the most severely affected limb showed the strongest atrophy, macroscopically, and displayed 4R tau‐immunoreactive GGIs and microscopically many ferritin‐immunoreactive neurons. We diagnosed this patient as having GGT. This is the first GGT case with iron deposition confirmed both radiologically and pathologically.

AMYLOID AND TAU IMAGING IN PATIENTS WITH POSTERIOR CORTICAL ATROPHY

P2-361 AMYLOID AND TAU IMAGING IN PATIENTS WITH POSTERIOR CORTICAL ATROPHY Akitoshi Takeda, Jun Takeuchi, Haruna Saito, Joji Kawabe, Yasuhiro Wada, Aya Mawatari, Hisashi Doi, Yasuyoshi Watanabe, Soichiro Kitamura, Hitoshi Shimada, Makoto Higuchi, Tetsuya Suhara, Yoshiaki Itoh, Osaka City University, Osaka, Japan; RIKEN Center for Life Science Technologies, Kobe, Japan; National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. Contact e-mail: a-taked@ med.osaka-cu.ac.jp

Localized Accumulation of Tau without Amyloid-Beta in Aged Brains Measured with [11C]PBB3 and [11C]Pib Positron Emission Tomography

Objective: Different regional specificity in tau accumulation is well known in Alzheimer’s disease (AD) brains. However, little is known about such distribution in aging brains and mild cognitive impairment (MCI) brains. Methods: Cognitive functions and regional accumulation of tau and amyloid β (Aβ) were evaluated in 13 healthy controls (HCs), 3 patients with MCI and 4 AD patients. Tau and Aβ accumulation was semi-quantitatively measured with positron emission tomography (PET) using [11C]pyridinyl-butadienyl-benzothiazole 3 (PBB3) and [11C]Pittsburgh compound-B (PiB). Results: Age-dependent accumulation of tau was found in all predetermined regions characteristic of AD, especially in the parahippocampal gyrus, lateral temporal cortex, frontal cortex, and posterior cingulate gyrus, where age-dependency was statistically significant. In contrast, age-dependency in accumulation of Aβ was not observed in most regions assessed in HC. Moreover, the accumulation of tau in regions characteristic of AD in MCI patients was higher than that in HC, whereas tau accumulation was highest and statistically significant in AD patients. Unlike HC, the accumulation of tau was accompanied by that of Aβ in patients with MCI and AD. Conclusion: Mild and age-dependent accumulation of tau without Aβ was found in AD-related areas in aging brains. Considering age as a major risk for AD, higher accumulation of tau may trigger the neurodegenerative process of AD.