Typical and atypical MRI abnormalities in Wernicke's encephalopathy: Correlation with blood vitamin B1 levels.

PURPOSE: Clinical features of Wernicke's encephalopathy (WE) confirmed strictly through the low blood vitamin B1 (VB1) levels are limited. This study aimed to analyse magnetic resonance imaging (MRI) findings, and clinical characteristics, in patients with WE who have confirmed low blood VB1 levels. METHODS: Clinical and laboratory records of 12 consecutive patients with WE admitted to our hospital during the past 11 years were reviewed. The WE diagnosis was confirmed based on low blood VB1 levels and the presence of at least one of the classical triad. RESULTS: Ophthalmoplegia and nystagmus were recorded in 75% and 50% of the patients, respectively. Eleven of 12 patients presented with consciousness disturbance/memory loss. All patients experienced gait disturbances. Eight of the 12 patients exhibited MRI abnormalities at typical sites (the dorsal midbrain [n = 7], medial thalamus [n = 6], mammillary bodies [n = 5], and dorsal pons [n = 5]). Of the 12 patients, six showed abnormalities at atypical sites (the splenium of the corpus callosum [n = 4], fornix [n = 3], cerebral cortex [n = 2], cerebellar vermis [n = 2], and dorsal medulla [n = 1]). Patients with positive MRI abnormalities had significantly lower blood VB1 levels than those without abnormalities (9.5 vs. 16.0 ng/mL). CONCLUSIONS: In cases of confirmed WE with low blood VB1 levels, the corpus callosum, fornix, and cerebral cortex were more frequently involved than in previous studies. MRI abnormalities at both typical and atypical sites were correlated with low blood VB1 levels in WE, suggesting that lower blood VB1 levels are associated with more severe brain damage in patients with WE.

Clinical features and recovery pattern of secondary hypokalaemic paralysis.

PURPOSE: Information regarding frequency, details of neurological signs and recovery patterns of patients with secondary hypokalaemic paralysis (HP) is limited. This study aimed to analyse the frequency, aetiology, clinical features and recovery patterns of patients with secondary HP. METHODS: The clinical and laboratory records of 18 consecutive patients with secondary HP aged ≥ 18 years admitted to our hospital between April 2011 and March 2022 were reviewed. Patients with inherited hypokalaemic periodic paralysis were excluded. RESULTS: Of the 18 patients, 16 had a common aetiology: chronic alcoholism, diarrhoea or an imbalanced diet. Initial symptoms, such as fatigue, were often atypical. Three patients had prominent asymmetric limb weakness and four had predominant upper limb weakness. On admission, the mean serum potassium and creatine kinase (CK) levels of the patients were 1.90 mmol/L and 4488 U/mL, respectively. Ten patients (56%) had decreased potassium levels after admission, despite potassium replacement treatment (rebound hypokalaemia). Twelve patients presented with increased CK levels even after 2-5 days (delayed hyperCKaemia). Low serum magnesium levels significantly correlated with rebound hypokalaemia. CONCLUSIONS: Secondary HP can be caused by a variety of conditions, but mainly occurs due to lifestyle conditions/disorders. Secondary HP often presents with atypical symptoms, and the initial symptoms can be non-specific. Rebound hypokalaemia and delayed hyperCKaemia are common in secondary HP, despite potassium replacement. As such, careful serial monitoring is needed for patients with secondary HP.

Unilateral Wing-Beating Tremor in Neuronal Intranuclear Inclusion Disease.

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.

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.

Brain 5-HT2A receptor binding and its neural network related to behavioral inhibition system.

The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

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.

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.

The Neuropsychological Correlates of Brain Perfusion and Gray Matter Volume in Alzheimer's Disease.

BACKGROUND: Neuropsychological tests, structural neuroimaging, and functional neuroimaging are employed as diagnostic and monitoring biomarkers of patients with Alzheimer's disease (AD)Objective:We aimed to elucidate the similarities and differences in neuropsychological tests and neuroimaging with the use of the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog), structural magnetic resonance image (MRI), and perfusion single photon emission computed tomography (SPECT), and parametric image analyses to understand its role in AD. METHODS: Clinically-diagnosed AD patients (n = 155) were scanned with three-dimensional T1-weighted MRI and N-isopropyl-p-[123I] iodoamphetamine SPECT. Statistical parametric mapping 12 was used for preprocessing images, statistical analyses, and voxel-based morphometry for gray matter volume analyses. Group comparison (AD versus healthy controls), multiple regression analyses with MMSE, ADAS-cog total score, and ADAS-cog subscores as variables, were performed. RESULTS: The AD group showed bilateral hippocampal volume reduction and hypoperfusion in the bilateral temporo-parietal lobe and posterior midline structures. Worse MMSE and ADAS-cog total score were associated with bilateral temporo-parietal volume loss and hypoperfusion. MMSE, but not ADAS-cog, was associated with the posterior midline structures. The ADAS-cog subscores were associated with the temporal volume, while perfusion analyses were linked to the left temporo-parietal region with the language function and right analogous region with the constructional praxis subscore. CONCLUSION: MMSE and ADAS-cog are associated with temporo-parietal regions, both in volume and perfusion. The MMSE score is associated with posterior midline structures and linked to an abnormal diagnostic AD pattern. Perfusion image analyses better represents the cognitive function in AD patients.

The Relationship Between the Striatal Dopaminergic Neuronal and Cognitive Function With Aging.

Both cognitive function and striatal dopamine function decline by normal aging. However, the relationship among these three factors remains unclear. The aim of this study was to elucidate the association among age-related changes in the striatal dopamine transporter (DAT) and cognitive function in healthy subjects. The 30 healthy volunteers were enrolled in this research, the age ranged from 41 to 82 (64.5 ± 11.5, mean ± SD). All subjects were scanned with both T1-weighted magnetic resonance imaging (MRI) and 123I-FP-CIT single-photon emission computed tomography (SPECT) images. The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) was used to evaluate cognitive function. Six spherical regions of interest (ROI) using 10 mm in diameter on the caudate nucleus, anterior putamen and posterior putamen were manually drawn on MRI image which was applied onto SPECT image. The relationship between striatal occipital ratio (SOR) values and WAIS-III subscore were analyzed by multiple regression analysis. Subscores which was significant were further analyzed by path analyses. Full intelligence quotient (IQ), verbal IQ, verbal comprehension were all positively correlated with age-adjusted striatal DAT binding (P < 0.01). Multiple regression analyses revealed that the coding digit symbol correlated with all striatal regions except for the left caudate (P < 0.04). Picture completion and right caudate, similarities and left caudate also showed a positive correlation (P < 0.04). Path analysis found that the right caudate and picture completion; the left caudate and similarities were correlated independently from age, whereas the models of coding digit symbol were not significant. These results suggest that age-based individual diversity of striatal DAT binding was associated with verbal function, and the caudate nucleus plays an important role in this association.

Decline in drawing ability and cerebral perfusion in Parkinson's disease patients after subthalamic nucleus deep brain stimulation surgery.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for alleviating motor symptoms in advanced Parkinson's disease (PD) patients; however, a postoperative decline in cognitive and speech function has become problematic although its mechanism remains unclear. The aim of the present study was to elucidate the properties of language and drawing ability and cerebral perfusion in PD patients after bilateral STN DBS surgery. METHODS: Western aphasia battery, including drawing as a subcategory, and perfusion (N-isopropyl-p-[123I] iodoamphetamine) SPECT scan was conducted in 21 consecutive PD patients, before, and three to six months after, bilateral STN DBS surgery while on stimulation. Perfusion images were compared with those of 17 age- and gender-matched healthy volunteers. In the parametric image analysis, the statistical peak threshold was set at P < 0.001 uncorrected with a cluster threshold set at P < 0.05 uncorrected. RESULTS: Although motor symptoms were improved and general cognition was preserved in the patient group, 11 patients (52.4%) showed a decline in the drawing subcategory after surgery, which showed a reduction in Frontal Assessment Battery score in this group of patients. Statistical parametric analysis of the brain perfusion images showed a decrease of cerebral blood flow in the prefrontal and cingulate cortex after surgery. Patients whose drawing ability declined showed decreased perfusion in the middle cingulate cortex comparing before and after surgery. CONCLUSION: Present results show that some PD patients show a decline in drawing ability after bilateral STN DBS which may attributable by dysfunction in the cingulate network.

Relapse numbers and earlier intervention by disease modifying drugs are related with progression of less brain atrophy in patients with multiple sclerosis.

Long term effect between disease-modifying drugs (DMDs) treatment duration and brain atrophy rate has not been fully investigated in patients with relapsing-remitting MS (RRMS). The aim of this study was to investigate whether DMDs could slow down the progression of brain atrophy in patients with RRMS by comparing DMDs-treated group with non-treated group during a certain period of time. This was a retrospective investigation. Forty-nine RRMS patients underwent two brain MRI scans more than one year apart. Between scans, patients were treated with fingolimod (n = 16), interferon-beta (n = 23) or not treated with DMD (n = 10). Correlations between clinical characteristics and brain volume were calculated by statistical parametric mapping-12. In all 49 patients, the total attack number before 1st MRI scan and the annualized rate of total lesion volume change between the two scans showed a positive correlation with annualized atrophy rate of grey matter volume (GMV) plus white matter volume (WMV). In patients with DMDs (n = 39), the period from drug initiation to 1st MRI scan was negatively correlated with the annualized atrophy rate of GMV + WMV and number of attacks between scans. The number of total previous attacks could be a predictor of subsequent MS progression. Early intervention by DMDs could prevent brain atrophy in patients with MS.

Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain.

OBJECTIVE: To assess the cerebral blood flow (CBF) in patients with diabetic neuropathic pain, and its changes after duloxetine therapy. METHODS: Using iodine-123-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (IMP-SPECT), we performed a cross-sectional study of 44 patients with diabetes, and compared CBF in those with (n = 24) and without neuropathic pain (n = 20). In patients with neuropathic pain, we also longitudinally assessed changes in CBF 3 months after treatment with duloxetine. RESULTS: IMP-SPECT with voxel-based analyses showed a significant increase in cerebral blood flow in the right anterior cingulate cortex and a decrease in the left ventral striatum in patients with neuropathic pain, compared with those without pain. After duloxetine treatment, volume of interest analyses revealed a decrease in cerebral blood flow in the anterior cingulate cortex in patients with significant pain relief but not in non-responders. Furthermore, voxel-based whole brain correlation analyses demonstrated that greater baseline CBF in the anterior cingulate cortex was associated with better pain relief on the numerical rating scale. CONCLUSIONS: Our results suggest that the development of neuropathic pain is associated with increased activity in the anterior cingulate cortex, and greater baseline activation of this region may predict treatment responsiveness to pharmacological intervention. TRIAL REGISTRATION NUMBER: UMIN000017130;Results.

[Functional Neuroimaging of Sweating].

Central mechanisms of thermal and emotional sweating has been elucidated by using functional MRI in healthy human subjects. The hypothalamus (preoptic region) was specifically activated during thermal sweating, whereas prefrontal regions, insula, and anterior cingulate were activated during emotional sweating. Both thermal and emotional sweating were associated with activation in the dorsal midbrain and in the rostral lateral medulla. These results suggested that sweating in human represents not only sympathetic activation but also integrates emotional function, internal awareness, and attentional arousal in humans.

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4(+) T Lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that favors the cerebrum and typically occurs in immunosuppressed patients. We herein report the case of a 66-year-old man with PML, idiopathic CD4(+) T lymphocytopenia (ICL), and chronic renal failure. Cranial magnetic resonance imaging (MRI) showed a crescent-shaped lesion in the left cerebellum, brainstem, and middle cerebellar peduncle. Although the patient did not present with HIV infection, collagen diseases, or tumors, JC virus DNA was detected in the cerebrospinal fluid. Clinicians should consider PML and ICL in the differential diagnosis if the patient develops progressive ataxia and a crescent-shaped cerebellar lesion on MRI.