Kazuya Kawabata

A questionnaire survey of general practitioners in Japan in relation to management of transient ischemic attack

A transient ischemic attack (TIA) is a medical emergency associated with a high risk of early ischemic stroke (1,2). General practitioners (GPs) play an important role in clinical management of TIA. The purpose of this study was to clarify the management of TIA among GPs in Japan. We conducted a choice questionnaire survey concerning TIA among 329 GPs in the Osaka area and 158 GPs in the Nagoya area. Figure 1 shows responses to the question related to “the strategy for patients who developed hemiparesis one hour ago. In cases where symptoms persisted at the time of visit, 85% of respondents in the Osaka area and 87% of respondents in the Nagoya area indicated that they would refer patients to a stroke specialty hospital immediately, and 5% in the Osaka area and 6% in the Nagoya area indicated that they would refer patients to a stroke specialty hospital, but not immediately. In contrast, among patients in whom symptoms disappeared at the time of the visit, 42% and 42%, and 36% and 35%, gave these respective responses (P < 0·001, P < 0·001). Most respondents (70% in the Osaka area and 63% in the Nagoya area) indicated that they had some difficulties with clinical management of patients with TIA, including lack of confidence regarding the diagnosis, lack of familiarity with referral criteria, and lack of knowledge about which hospitals to use for referral. This survey suggests that GPs in Japan seem to regard TIA as less of a medical emergency than stroke, and that most GPs had some troubles managing patients with TIA. Results were similar in two areas. It is necessary to enlighten GPs about the importance of immediate assessment and treatment after TIA, and to establish a close relationship between GPs and stroke specialty hospitals.

Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson’s disease

Objective Severe hyposmia is a risk factor of dementia in Parkinson’s disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients with severe hyposmia (PD-SH) are unclear. Methods We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH), and 15 healthy controls (HCs). Results Decreased gray matter volume (GMV) was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke’s Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH. Conclusion PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

Early detection of speech and voice disorders in Parkinson’s disease patients treated with subthalamic nucleus deep brain stimulation: a 1-year follow-up study

We previously reported that Parkinson’s disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) had distinct phenotypes of speech and voice disorders: hypokinetic dysarthria, stuttering, breathy voice, strained voice, and spastic dysarthria. However, changes over time remain unclear. In the present study, 32 consecutive PD patients were assessed before and up to 1xa0year after surgery (PD-DBS). Eleven medically treated PD patients were also assessed (PD-Med). Speech, voice, motor, and cognitive functions were evaluated. At baseline, the incidence of hypokinetic dysarthria (63% of PD-DBS vs. 82% of PD-Med), stuttering (50% vs. 45%), breathy voice (66% vs. 73%), and strained voice (3% vs. 9%) was similar between groups. At 1xa0year, a slight but significant deterioration in speech intelligibility (pxa0<xa00.001) and grade of dysphonia (pxa0=xa00.001) were observed only in PD-DBS group compared with baseline. During the follow-up, stuttering (9% vs. 18%) and breathy voice (13% vs. 9%) emerged in PD-DBS and PD-Med, but strained voice (28%) and spastic dysarthria (44%) emerged only in PD-DBS. After the stimulation was stopped, strained voice and spastic dysarthria improved in most patients, while stuttering and breathy voice improved in a minority of patients. These findings indicate that the most common DBS-induced speech and voice disorders are strained voice and spastic dysarthria and that STN-DBS potentially aggravates stuttering and breathy voice. An improved understanding of these types of disorders may help detect speech and voice deteriorations during the early phase and lead to appropriate treatments.

Vasculitic Neuropathy Following Exposure to a Glyphosate-based Herbicide

We herein report a case of peripheral neuropathy following exposure to large amounts of glyphosate-based herbicide. A 70-year-old man suffered from pain and purpura in the left sole following exposure to glyphosate-based herbicide. Pain and purpura spread to the opposite side and increased in severity. Mild weakness of the lower limbs was also observed. A sural nerve biopsy revealed the infiltration of lymphocytes around small vessels in the epineurium with numerous eosinophils, deposition of hemosiderins and focal axonal degeneration, compatible with findings of vasculitic neuropathy. Glyphosate-based herbicides should be recognized as a causative agent of vasculitic neuropathy.

An unbiased data-driven age-related structural brain parcellation for the identification of intrinsic brain volume changes over the adult lifespan

ABSTRACT This study aims to elucidate age‐related intrinsic brain volume changes over the adult lifespan using an unbiased data‐driven structural brain parcellation. Anatomical brain images from a cohort of 293 healthy volunteers ranging in age from 21 to 86 years were analyzed using independent component analysis (ICA). ICA‐based parcellation identified 192 component images, of which 174 (90.6%) showed a significant negative correlation with age and with some components being more vulnerable to aging effects than others. Seven components demonstrated a convex slope with aging; 3 components had an inverted U‐shaped trajectory, and 4 had a U‐shaped trajectory. Linear combination of 86 components provided reliable prediction of chronological age with a mean absolute prediction error of approximately 7.2 years. Structural co‐variation analysis showed strong interhemispheric, short‐distance positive correlations and long‐distance, inter‐lobar negative correlations. Estimated network measures either exhibited a U‐ or an inverted U‐shaped relationship with age, with the vertex occurring at approximately 45–50 years. Overall, these findings could contribute to our knowledge about healthy brain aging and could help provide a framework to distinguish the normal aging processes from that associated with age‐related neurodegenerative diseases. HighlightsAn unbiased, data‐driven brain parcellation was generated using anatomical images and ICA.Most parcels showed strong negative correlation with age with significant regional variations.Linear combination of parcels reliably predicted chronological age with mean error of 7.2 years.Structural co‐variation analysis showed positive and negative inter‐regional GM correlations.Structural network measures exhibited U‐ or inverted U‐shaped relation with age.

Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy

ObjectiveWe examined the anatomical involvement related to cognitive impairment in patients with multiple system atrophy (MSA).MethodsWe examined 30 patients with probable MSA and 15 healthy controls. All MSA patients were assessed by the Unified MSA-Rating scale and Addenbrooke’s Cognitive Examination-Revised (ACE-R). We classified 15 MSA patients with ACE-R scoresu2009>u200988 as having normal cognition (MSA–NC) and 15 with scoresu2009≤u200988 as having cognitive impairment (MSA–CI). All subjects underwent 3xa0T MRI scanning and were investigated using voxel-based morphometry and diffusion tensor imaging.ResultsBoth the MSA–NC and MSA–CI patients exhibited cerebellar but not cerebral atrophy in voxel-based morphometry compared to controls. In contrast, tract-based spatial statistics revealed widespread and significantly decreased fractional anisotropy (FA) values, as well as increased mean diffusivity, radial diffusivity, and axial diffusivity in both the cerebrum and cerebellum in MSA–CI patients compared to controls. MSA–NC patients also exhibited similar involvement of the cerebellum but less extensive involvement of the cerebrum compared with the MSA–CI patients. In particular, FA values in MSA–CI patients were significantly decreased in the anterior part of the left corpus callosum compared with those in MSA–NC patients. The mean FA values in the left anterior part of the corpus callosum were significantly correlated with total ACE-R scores and subscores (memory, fluency, and language) in MSA patients.ConclusionsDecreased FA values in the anterior corpus callosum showed a significant correlation with cognitive impairment in MSA.

Distinct manifestation of cognitive deficits associate with different resting-state network disruptions in non-demented patients with Parkinson’s disease

Cognitive deficits in Parkinson’s disease (PD) are heterogeneous entities, but a relationship between the heterogeneity of cognitive deficits and resting-state network (RSN) changes remains elusive. In this study, we examined five sub-domain scores according to Addenbrooke’s Cognitive Examination-Revised (ACE-R) for the cognitive evaluation and classification of 72 non-demented patients with PD. Twenty-eight patients were classified as PD with normal cognition (PD-NC). The remaining 44 were subdivided into the following 2 groups using a hierarchical cluster analysis: 20 with a predominant decrease in memory (PD with amnestic cognitive deficits: PD-A) and 24 with good memory who exhibited a decrease in other sub-domains (PD with non-amnestic cognitive deficits: PD-NA). We used an independent component analysis of RS-fMRI data to investigate the inter-group differences of RSN. Compared to the controls, the PD-A showed lower FC within the ventral default mode network (vDMN) and the visuospatial network. On the other hand, the PD-NA showed lower FC within the visual networks and the cerebellum–brainstem network. Significant differences in the FC within the vDMN and cerebellum–brainstem network were observed between the PD-A and PD-NA, which provided a good discrimination between PD-A and PD-NA using a support vector machine. Distinct patterns of cognitive deficits correspond to different RSN changes.

Clinical and Imaging Features of Multiple System Atrophy: Challenges for an Early and Clinically Definitive Diagnosis

Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder. Patients with MSA show various phenotypes during the course of their illness, including parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal signs. Patients with MSA sometimes present with isolated autonomic failure or motor symptoms/ signs. The median duration from onset to the concomitant appearance of motor and autonomic symptoms is approximately 2 years but can range up to 14 years. As the presence of both motor and autonomic symptoms is essential for the current diagnostic criteria, early diagnosis is difficult when patients present with isolated autonomic failure or motor symptoms/signs. In contrast, patients with MSA may show severe autonomic failure and die before the presentation of motor symptoms/signs, which are currently required for the diagnosis of MSA. Recent studies have also revealed that patients with MSA may show nonsupporting features of MSA such as dementia, hallucinations, and vertical gaze palsy. To establish early diagnostic criteria and clinically definitive categorization for the successful development of disease-modifying therapy or symptomatic interventions for MSA, research should focus on the isolated phase and atypical symptoms to develop specific clinical, imaging, and fluid biomarkers that satisfy the requirements for objectivity, for semi- or quantitative measurements, and for uncomplicated, worldwide availability. Several novel techniques, such as automated compartmentalization of the brain into multiple parcels for the quantification of gray and white matter volumes on an individual basis and the visualization of α-synuclein and other candidate serum and cerebrospinal fluid biomarkers, may be promising for the early and clinically definitive diagnosis of MSA.

Involvement of the Precuneus/Posterior Cingulate Cortex Is Significant for the Development of Alzheimer’s Disease: A PET (THK5351, PiB) and Resting fMRI Study

Background: Imaging studies in Alzheimer’s disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

EFFECTS OF AEROBIC TRAINING ON FUNCTIONAL CONNECTIVITY IN THE BRAINS OF OLDER ADULTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT

impairment at low genetic risk for Alzheimer’s (defined as APOE ε4 non-carriers), long-term statin-use was associated with lower tau (p1⁄40.033) and marginally non-significantly associated with lower amyloid (p1⁄40.073), with both analyses significant (p1⁄40.030 and p1⁄40.029) after controlling for mid-life dyslipidemia. Conclusions: In this study, long-term statin use was associated with changes in white matter tract integrity even in the absence of changes in overall WMH. Our findings also suggest that statins may have clinical subpopulation-specific protective effects on amyloid and tau deposition. As an avenue to individualized therapy, additional study is warranted to clarify the likely complex interactions of statins with genetic and acquired comorbid factors.