Relationship between BPSD and regional cortical volume in dementia

　認知症の症状，特に BPSD は罹患した本人のみならずその家族や周りの人の生活，QOL にも影響を与える．BPSD は中核症状と環境要因，身体要因，心理要因などの相互作用によって起こることが多く症状の軽重には個人差もあることからその発症予測は難しい．BPSD 発症に関わる神経基盤の理解とその発症リスク予測につながる客観的な指標の確立のための探索的検討として， BPSD の発症と脳の構造的変化との関連を検討する目的で，MRI データにおける大脳皮質の局所容積変化を BPSD 発症の有無で比較し，BPSD 発症に関連する脳領域の検討を行った．川崎医科大学附属病院脳神経内科ものわすれ外来を受診した患者20名（平均74.8歳，男性５名）を対象に年齢，性別，認知機能（MMSE-J，FAB），うつ（GDS-15-J），BPSD の程度（阿倍式 BPSD スコア： ABS）を用い，BPSD の有無（ABS：０vs１以上）によって患者を２群に分け患者背景，臨床指標評価を比較した．また同時期に測定した MRI 3DT1画像データを使用し，SPM12ソフトウェアを用いて患者の灰白質，白質，脳脊髄液領域を分離し，解剖学的標準化を行って灰白質容積の群間差を検討した．結果，年齢，性別，MMSE，FAB，GDS は両群間で有意差を認めなかった．灰白質容積の群間差の検討では，BPSD あり群では右中前頭回（BA6），右下前頭回三角部（BA45）の灰白質容積が有意に低下していた．BA6と BA45における ABS と灰白質容積にはそれぞれ負の相関があった．認知症患者の BPSD 発症が右前頭葉皮質の灰白質容積低下が関連している可能性が示唆された．先行研究により BA6は他者の意図を推察する心の理論課題に関与し，BA45の灰白質容積の低下は統合失調症患者における妄想や陽性症状との相関が示唆されている．今後 BPSD の発症予測や個別治療の可能性につながる重要な知見と考えられ，今後の研究の進展が期待される．　Symptoms of dementia, especially Behavioral and Psychological Symptom of Dementia (BPSD), affect the quality of life of not only patients but also family members and caregivers. Underlying mechanisms of BPSD is still unknown but multiple factors including cognitive impairments as well as environmental, physical, and psychological factors may cause BPSD and the severity of symptoms varies individually. In this study, we aimed to investigate the underlying neural mechanisms for emerging BPSD by comparing the regional volume change of the cerebral cortex in patients with or without BPSD to identify the cortical region critical for emerging BPSD. We evaluated 20 patients (average age 74.8, M5) who visited our memory clinic for their age, gender, cognitive function (MMSE-J, FAB), depression (GDS-15-J), and BPSD (ABS) degree. We divided patients into two groups according to the presence of BPSD (ABS: 0 vs 1 or higher) and background characteristics and clinical indicators were compared. Using 3DT1 image data acquired by 3-Tesla MRI apparatus, we segmented the patient’s brain into gray matter, white matter, and cerebrospinal fluid. After anatomical normalization, we conducted group-wise comparison between patients with and without BPSD to investigate cortical area associated with emerging BPSD. Patients’characteristics and baseline cognitive factiors including Age, sex, MMSE-J, FAB, and GDS-15-J showed no significant difference between the two groups. The gray matter volume of the right middle frontal gyrus (BA6) and the right lower frontal gyrus triangle (BA45) were significantly reduced in the patients with BPSD. Furthermore, in BA6 and BA45, there were negative correlation between severity of BPSD and gray matter volumes suggesting possible association between gray matter volume in the right frontal cortex and BPSD. Previous studies have shown that BA6 is associated with the Theory of Mind, and that a decrease in the gray matter volume of BA45 is correlated with delusions and positive symptoms in patients with schizophrenia. This is an important finding that leads to the prediction of the onset of BPSD and the possibility of individual treatment

Current status and problems of elderly drivers in our outpatient clinic

　当院では平成29年３月12日の道路交通法改正を踏まえて平成29年４月より，もの忘れ外来とは別に「運転免許外来」を新設し，時間をかけた丁寧な診療と告知，指導，運転免許返納後の生活確保・支援ができるよう，多職種で受診者に対応している．平成31年４月までの運転免許外来受診者は31人で，平均年齢80.07±3.91歳．第一分類該当者19人，交通違反での紹介３人で，その他は自発的な受診であった．10例は既に事故を起こし，６例は既に抗認知症薬を内服していた . 受診者のほとんどが，通院，買い物，農作業など運転中止後の生活が困るとの理由から，運転継続を希望した．神経心理検査では，MMSE-J 22.32/30±3.87, Kohs IQ 66.42±11.87, DASC-21 29.53±7.07, CDR 0.58±0.19と比較的認知機能低下が軽度な者が多かった．頭部 MRI では20例に陳旧性脳梗塞や脳挫傷，12例に脳萎縮を認め，123I-IMP 脳血流 SPECT では14例にアルツハイマー病を示唆する脳血流低下を認めた．診断後，全例に運転免許返納を推奨したが，自発的に運転中止に至った例は９例のみであった．かかりつけ医による診断書作成が普及し自主返納事例も増加したためか，当院の受診者数ならびに運転免許取り消し処分となる事例は外来開設当初の予想より少なかった．認知機能低下は認めるものの明らかな認知症に至っていない MCI 症例については，診断書提出後も運転継続している事例が多かった．運転継続希望者に丁寧に現制度の意義を説明し，移動手段の確保や生活支援について地域で相談できる体制作りが必要である．　Following the revision of the Road Traffic Act, which obligates elderly drivers to undergo cognitive screening tests at license renewal, we established a new outpatient memory clinic specializing in issues surrounding elderly drivers’ driver licenses. In this new outpatient clinic, we provide guidance and information about supporting resources for life after returning their driver’s licenses and the usual medical care and education. In the past two years, 31 patients, with an average age of 80.1±3.9 years, visited this clinic. Among these, 19 were referred to our clinic because of impaired cognition by screening test (the first classification), three were referred us for traffic violations and the others visited voluntarily. Among these 31 patients, ten had already experienced car accidents and six had already been prescribed cholinesterase inhibitors. Neuropsychological examination revealed mildly impaired cognitive function including MMSE-J 22.3±3.9, Kohs IQ 66.4±11.9, DASC-21 29.5±7.1 and CDR 0.58 ±0.19. Brain MRI revealed significant brain atrophy in 20 patients and brain contusions in 12. 123I-IMP SPECT showed decreased cerebral blood flow in 14 patients. Although driving is necessary for most patients to maintain activities of daily living and quality of life, we recommended all to stop driving based on the revised Road Traffic Act, which restricts driving by people with dementia. However, only nine patients suspended their driving and returned their licenses voluntarily; most MCI patients continued driving even after diagnosis. More effort is necessary to persuade patients of the significance of the current system, as is a social system that offers alternative means of transportation and supports patients in their lives in their local community

Temporal dispersion in vasculitic neuropathy: its microscopic ultrastructural findings

　症例は35歳男性．32歳のときに右腓腹神経・足底神経支配領域の異常感覚で発症し，その後，左腓腹神経・足底神経領域，両側尺骨神経領域に感覚障害が拡大した．神経伝導検査では，左脛骨神経複合筋活電位において，時間的分散の所見が認められた．腓腹神経生検では，神経上膜にフィブリノイド壊死を伴う壊死性血管炎を認めた．エポン包埋トルイジン青染色では、有髄神経線維の脱落が著明であり，髄鞘の薄い再生軸索が認められた．電子顕微鏡による観察では，脱髄は認められず，軸索の再生が認められたが，髄鞘再生に乏しい thin myelin が特徴的であった．神経伝導検査で，伝導ブロックや時間的分散といった脱髄を疑う所見を呈する血管炎性ニューロパチーについて24例の報告があるが，これまで電子顕微鏡による観察はされていない．血管炎性ニューロパチーによって惹起される時間的分散の出現機序について，微細構造所見を基に考察する．　A previously healthy 35-year-old man developed abnormal sensation in the right sural and medial plantar nerve territory 2 years ago. The sensory impairment gradually spread to the left sural and medial plantar nerve regions, then bilateral ulnar nerve regions. Nerve conduction study showed temporal dispersion in the left tibial nerve. Sural nerve biopsy revealed necrotizing vasculitis with fibrinoid necrosis in the epineurium. Toluidine blue staining of Epon-embedded tissue showed significant loss of myelinated nerve fibers without demyelination, even in the teased nerve fiber preparations. Electron microscopy showed immature regenerated nerve fibers with thin myelin sheaths. Even including 24 reported cases of vasculitic neuropathy with either conduction block, pseudo-conduction block, or temporal dispersion, this is the first case examined by electron microscopy. Herein, we discuss the ultrastructural background of“temporal dispersion”in vasculitic neuropathy

Neurofeedback Using Real-Time Near-Infrared Spectroscopy Enhances Motor Imagery Related Cortical Activation

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients

Effect of dual-task interaction combining postural and visual perturbations on cortical activity and postural control ability

Previous studies have suggested cortical involvement in postural control in humans by measuring cortical activities and conducting dual-task paradigms. In dual-task paradigms, task performance deteriorates and can be facilitated in specific dual-task settings. Theoretical frameworks explaining these dual-task interactions have been proposed and debated for decades. Therefore, we investigated postural control performance under different visual conditions using a virtual reality system, simultaneously measuring cortical activities with a functional near-infrared spectroscopy system. Twenty-four healthy participants were included in this study. Postural stability and cortical activities after perturbations were measured under several conditions consisting of postural and visual perturbations. The results showed that concurrent visual and postural perturbations could facilitate cortical activities in the supplementary motor area and superior parietal lobe. Additionally, visual distractors deteriorated postural control ability and cortical activation of the supplementary motor area. These findings supported the theoretical framework of the “Cross talk model”, in which concurrent tasks using similar neural domains can facilitate these task performances. Furthermore, it indicated that the cortical resource capacity and domains activated for information processing should be considered in experiments involving dual-task paradigms and training

Optical brain imaging and its application to neurofeedback

Besides passive recording of brain electric or magnetic activity, also non-ionizing electromagnetic or optical radiation can be used for real-time brain imaging. Here, changes in the radiation’s absorption or scattering allow for continuous in vivo assessment of regional neurometabolic and neurovascular activity. Besides magnetic resonance imaging (MRI), over the last years, also functional near-infrared spectroscopy (fNIRS) was successfully established in real-time metabolic brain imaging. In contrast to MRI, fNIRS is portable and can be applied at bedside or in everyday life environments, e.g., to restore communication and movement. Here we provide a comprehensive overview of the history and state-of-the-art of real-time optical brain imaging with a special emphasis on its clinical use towards neurofeedback and brain-computer interface (BCI) applications. Besides pointing to the most critical challenges in clinical use, also novel approaches that combine real-time optical neuroimaging with other recording modalities (e.g. electro- or magnetoencephalography) are described, and their use in the context of neuroergonomics, neuroenhancement or neuroadaptive systems discussed

Association of the Yips and Musculoskeletal Problems in Highly Skilled Golfers: A Large Scale Epidemiological Study in Japan

The yips are a set of conditions associated with intermittent motor disturbances that affect precision movement, especially in sports. Specifically, skilled golfers suffer from the yips, although its clinical characteristics and pathophysiology have not been well-studied. We surveyed skilled golfers to characterize their yips-related symptoms, to explore potential confounding factors associated with the yips. Golfers’ demographic information, golfing-career-related history, musculoskeletal status and manifestations of the yips are surveyed. Among the 1576 questionnaires distributed, 1457 (92%) responses were received, of which 39% of golfers had experienced the yips. The median age and golfing careers were 48 and 28 years, respectively. Golfers who had experienced the yips were older and had longer golfing careers and more frequent musculoskeletal problems than those without experience of the yips. The multivariate logistic regression analysis revealed that a longer golfing career and musculoskeletal problems were independent factors associated with yips experience. More severe musculoskeletal problems were associated with higher odds of experiencing the yips. A positive association between the yips and musculoskeletal problems was also observed. The yips have similar characteristics to task-specific movement disorders, with a detrimental effect caused by excessive repetition of a routine task. These findings support the notion that the yips are a type of task-specific dystonia

Influence of placement sites of the active recording electrode on CMAP configuration in the trapezius muscle

Objective: We investigated how the active electrode placement site influences compound muscle action potential (CMAP) configuration of the upper trapezius muscle (TM). Methods: A nerve conduction study of the accessory nerve was performed, and the CMAPs obtained with two different placement sites, i.e., placement of the active recording electrode on the belly of the upper TM (CMAP-A) and placement of the electrode 2 cm behind the belly (CMAP-B), were compared. CMAPs were also obtained with the active recording electrode placed in the supraspinous fossa (CMAP-C). Results: All CMAPs were recorded from 21 healthy volunteers. The mean peak-to-peak amplitude of CMAP-B was 3.4 mV higher than that of CMAP-A (11.0 ± 4.0 mV vs. 14.4 ± 4.9 mV; P < 0.01). The mean peak-to-peak amplitude of CMAP-C was 10.3 ± 5.0 mV. Conclusions: CMAP of the upper TM was always higher when the active recording electrode was placed 2 cm behind the belly of the muscle. Significance: When stimulating the accessory nerve, a current spread occurs to the C5 spinal nerve root and another CMAP originating from the supraspinatus muscle occurs in the supraspinous fossa. The volume conduction from the supraspinatus muscle affects the active recording electrode on the TM, resulting in an increase in CMAP amplitude. Keywords: Active recording electrode, Compound muscle action potential, Nerve conduction study, Supraspinatus muscle, Trapezius muscle, Volume conductio