Effect of Neurofeedback Facilitation on Poststroke Gait and Balance Recovery: A Randomized Controlled Trial.

OBJECTIVE: To test the hypothesis that supplementary motor area (SMA) facilitation with functional near-infrared spectroscopy-mediated neurofeedback (fNIRS-NFB) augments poststroke gait and balance recovery, we conducted a 2-center, double-blind, randomized controlled trial involving 54 Japanese patients using the 3-meter Timed Up and Go (TUG) test. METHODS: Patients with subcortical stroke-induced mild to moderate gait disturbance more than 12 weeks from onset underwent 6 sessions of SMA neurofeedback facilitation during gait- and balance-related motor imagery using fNIRS-NFB. Participants were randomly allocated to intervention (28 patients) or placebo (sham: 26 patients). In the intervention group, the fNIRS signal contained participants' cortical activation information. The primary outcome was TUG improvement 4 weeks postintervention. RESULTS: The intervention group showed greater improvement in the TUG test (12.84 ± 15.07 seconds, 95% confidence interval 7.00-18.68) than the sham group (5.51 ± 7.64 seconds, 95% confidence interval 2.43-8.60; group difference 7.33 seconds, 95% CI 0.83-13.83; p = 0.028), even after adjusting for covariates (group × time interaction; F 1.23,61.69 = 4.50, p = 0.030, partial η2 = 0.083). Only the intervention group showed significantly increased imagery-related SMA activation and enhancement of resting-state connectivity between SMA and ventrolateral premotor area. Adverse effects associated with fNIRS-mediated neurofeedback intervention were absent. CONCLUSION: SMA facilitation during motor imagery using fNIRS neurofeedback may augment poststroke gait and balance recovery by modulating the SMA and its related network. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with gait disturbance from subcortical stroke, SMA neurofeedback facilitation improves TUG time (UMIN000010723 at UMIN-CTR; umin.ac.jp/english/).

Concomitant improvement in anti-saccade success rate and postural instability gait difficulty after rTMS treatment for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological disorder characterised by motor and non-motor deficits. Repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex at a high frequency (5 Hz or higher) is reported to be a potential treatment of PD. We aimed to assess the effect of rTMS on eye movement control in patients with PD in their 'on' state. We enrolled 14 patients with PD and assessed motor symptoms (Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale; MDS-UPDRS) and eye movement performances (visually guided saccades, volitional anti-saccades, and small involuntary saccades during fixation) at baseline and after administering bilateral 10 Hz rTMS on leg region of the motor cortex. We confirmed that rTMS improved the MDS-UPDRS motor scores and found that rTMS improved the anti-saccade success rate, which requires adequate inhibition of the reflexive response. The improvement in anti-saccade success rate was correlated with that of the postural instability gait difficulty (PIGD) sub-scores of MDS-UPDRS and lower baseline Japanese version of the Montreal Cognitive Assessment scores. This result is consistent with previous findings that PIGD and inhibitory control deficits share common brain dysfunctions in PD. rTMS may alleviate dysfunctions of that circuit and have a clinical effect.

Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.

α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson's disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based assays are time-consuming procedures, and the clinical significance of the diversity of seeding activity among patients remains to be clarified. Previously, we reported a high-throughput ultrasonication-induced amyloid fibrillation assay. Here, we adapted this assay to amplify and detect α-synuclein aggregates from CSF, and investigated the correlation between seeding activity and clinical indicators. We confirmed that this assay could detect α-synuclein aggregates prepared in vitro and also aggregates released from cultured cells. The seeding activity of CSF correlated with the levels of α-synuclein oligomers measured by an enzyme-linked immunosorbent assay. Moreover, the seeding activity of CSF from patients with Parkinson's disease was higher than that of control patients. Notably, the lag time of patients with Parkinson's disease was significantly correlated with the MIBG heart-to-mediastinum ratio. These findings showed that our ultrasonication-based assay can rapidly amplify misfolded α-synuclein and can evaluate the seeding activity of CSF.

Involvement of cortical dysfunction in frequent falls in patients with Parkinson's disease.

INTRODUCTION: Gait and balance disorders are common clinical features of Parkinson's disease (PD). Although falls significantly affect the activities of daily living (ADL) and quality of life (QOL) of patients with PD, the underlying neural mechanisms associated with frequent falls in PD patients are still unclear. METHODS: Hypothesizing that the cerebral cortex would contribute to frequent falls in PD, we obtained 3D T1-weighted images from 91 non-dementia patients with PD and performed voxel-based morphometric analysis (VBM). Gray matter volume was compared between patients with and without frequent falls to investigate the structural basis for frequent falls in PD. As an ancillary analysis, we also performed resting-state functional magnetic resonance analysis using data from 58 patients. RESULTS: Among the 91 patients, 36 had experienced frequent falls. Gray matter volume in the right superior temporal gyrus (STG) and the right inferior parietal lobule (IPL) of these patients was significantly lower than that of the non-frequent fallers. There was also a significant correlation between fall frequency and gray matter volume in these two regions. Additionally, resting-state functional analysis revealed lower connectivity in the right posterior perisylvian region, including in the IPL and STG, in frequent fallers than in non-frequent fallers. CONCLUSION: Frequent falls in PD are associated with structural and functional abnormality of the cerebral cortex including the right IPL and STG.

[Analysis of PEG-J associated complications in 14 adult patients treated with levodopa-carbidopa intestinal gel].

We analyzed 14 patients in our hospital, who underwent levodopa-carbidopa intestinal gel (LCIG) treatment through a percutaneous endoscopic gastrojejunostomy (PEG-J). The PEG-J related complications were observed in 10 patients (71.4%). Detailed complications are as followings: J-tube related complications such as kinking (3 cases, 21.4%), pump malfunctions (3 cases, 21.4%), skin troubles in the gastrostoma (7 cases, 50.0%), duodenal perforation, peritonitis, and ulcers (2 cases, 14.3%). These results indicated that the sufficient care for PEG-J associated complications are important in LCIG treatment.

Effect of muscle strengthening exercise and time since onset in patients with amyotrophic lateral sclerosis: A 2-patient case series study.

Exercise for patients with amyotrophic lateral sclerosis (ALS) can be expected to improve function at the early stage of disease, but improvement cannot be expected at the late stage. However, no report has investigated the correlation between the effect of exercise and time since onset. This study examined the relevance between the effect of muscle strengthening exercise and time since onset in patients with ALS.This study is a retrospective nonconsecutive case series study at a single university hospital. We included 2 patients with ALS who were admitted twice. Case 1 was a 60-year-old man with the bulbar type. He was hospitalized 10 months (ALS functional rating scale-revised, 42 points) and 1 year and 8 months (33 points) after onset. Case 2 was a 52-year-old man with the lower limb type. He was hospitalized 1 year and 3 months (44 points) and 1 year and 8 months (33 points) after onset. Physical therapy was implemented daily on weekdays for approximately 30 minutes. The intervention period was 2 weeks. Lower limb muscle strengthening exercises were mainly performed and exercise intensity was adjusted to a modified Borg Scale score of 5 (lower limbs). The study investigated knee extension muscle strength (KEMS) by using a hand-held dynamometer and Functional Ambulation Categories (FAC) at the start and end of physical therapy during each hospitalization.KEMS improved during the initial hospitalization in both patients, and FAC improved in Case 2; neither KEMS nor FAC improved during rehospitalization in either patient. In Case 1, KEMS was maintained for 10 months.The current results suggest that the positive effect of muscle strengthening exercise is greater at the early stage and may be maintained in patients with bulbar type ALS. In addition, improvement can be achieved approximately 1 year after onset and in patients with an ALSFRS-R score of 40 points or more. Therefore, it is necessary to initiate and continue exercise earlier after onset.

Rehabilitation for a patient with anti-Yo antibody-positive paraneoplastic cerebellar degeneration caused by breast cancer: A case report and literature review.

RATIONALE: Rehabilitation for paraneoplastic cerebellar degeneration (PCD) has been indicated as necessary. However, there are only a few reports on rehabilitation in PCD. We describe the course of physical and cognitive functions and activities of daily living (ADL) in a patient with PCD and examine the effect of rehabilitation, along with a review of relevant literature. PATIENT CONCERNS: A 42-year-old woman experienced rapid deterioration in cerebellar symptoms and was unable to walk. The cerebellar symptoms improved after mastectomy, which was performed 3 months after the onset of symptoms. However, the cerebellar symptoms exacerbated 11 months after the onset of symptoms. She underwent immunotherapy because the level of anti-Yo antibodies was high, and anti-glutamic acid decarboxylase antibodies were detected. DIAGNOSES: She was diagnosed with anti-Yo antibody-positive PCD caused by breast cancer. INTERVENTIONS: Rehabilitation was performed preoperatively, postoperatively, and at 1 year after the onset of symptoms. OUTCOMES: Her physical function and ADL improved after the surgery and at 1 year after the onset of symptoms. Finally, she regained the ability to walk between parallel bars supported with one hand and a walking frame. LESSONS: Given the results of this case and the relevant literature, it appears that rehabilitation improves physical function and ADL after oncotherapy. Particularly, initiating treatment within three months of onset of symptoms may enable patients to walk without assistance.

[Questionnaire survey of musician's dystonia among students of a music college].

Musician's dystonia is known as a task specific dystonia. Though it is thought to occur during a long course of repetitive performance, the actual circumstances that precipitate this condition are not clear. According to factual reports this disease is not commonly known, probably because many of these patients may not have been visiting a hospital. We prepared a questionnaire and did a survey among the students of a music college. This is the first questionnaire survey aimed at finding out the prevalence of musician's dystonia among the students of music. Among the 480 participants of this survey, 29% of the students had knowledge of this disorder and 1.25% of the students had dystonia while performing music.

Reduced tongue pressure against the hard palate on the paralyzed side during swallowing predicts Dysphagia in patients with acute stroke.

BACKGROUND AND PURPOSE: Dysphagia is important for prognosis in patients with stroke because this condition can cause aspiration pneumonia or nutritional deficits. The present study investigated the relationship between tongue motor deficits and dysphagia in patients with acute stroke. METHODS: Maximal tongue pressure on the hard palate when swallowing 5 mL of water was measured using a T-shaped sensor sheet with 5 measuring points in 33 dysphagic and 31 nondysphagic patients with acute stroke. Maximum tongue pressures at each measuring point were compared between dysphagic and nondysphagic groups and between paralyzed and nonparalyzed sides. RESULTS: Tongue pressure at each measuring point was significantly smaller in dysphagic patients than in nondysphagic patients with the largest significant difference on the paralyzed side. The magnitude of tongue pressure to predict dysphagia was calculated as 4.6 kPa on the paralyzed side, offering 71.4% sensitivity and 72.3% specificity. CONCLUSIONS: Reduced tongue pressure on the paralyzed side may predict dysphagia in patients with acute stroke.

Note: Unshielded bilateral magnetoencephalography system using two-dimensional gradiometers.

Magnetoencephalography (MEG) noninvasively measures neuronal activity with high temporal resolution. The aim of this study was to develop a new type of MEG system that can measure bilateral MEG waveforms without a magnetically shielded room, which is an obstacle to reducing both the cost and size of an MEG system. An unshielded bilateral MEG system was developed using four two-dimensional (2D) gradiometers and two symmetric cryostats. The 2D gradiometer, which is based on a low-T(c) superconducting quantum interference device and wire-wound pickup coil detects a magnetic-field gradient in two orthogonal directions, or ∂/∂x(∂(2)B(z)/∂z(2)), and reduces environmental magnetic-field noise by more than 50 dB. The cryostats can be symmetrically positioned in three directions: vertical, horizontal, and rotational. This makes it possible to detect bilateral neuronal activity in the cerebral cortex simultaneously. Bilateral auditory-evoked fields (AEF) of 18 elderly subjects were measured in an unshielded hospital environment using the MEG system. As a result, both the ipsilateral and the contralateral AEF component N100m, which is the magnetic counterpart of electric N100 in electroencephalography and appears about 100 ms after the onset of an auditory stimulus, were successfully detected for all the subjects. Moreover, the ipsilateral P50m and the contralateral P50m were also detected for 12 (67%) and 16 (89%) subjects, respectively. Experimental results demonstrate that the unshielded bilateral MEG system can detect MEG waveforms, which are associated with brain dysfunction such as epilepsy, Alzheimer's disease, and Down syndrome.

Ulcerated plaques in the aortic arch contribute to symptomatic multiple brain infarction.

BACKGROUND: The configuration of aortic plaque appears to be as important as its thickness when it acts as an embolic source to the brain. The frequency and clinical predictors of ulcerated plaque at the aortic arch identified using transoesophageal echocardiography (TOE) in patients with stroke were determined, and the association between the ulcer and recent ischaemic stroke, particularly multiple brain infarcts, which appear to indicate embolic stroke, was examined. METHODS: Aortic and cardiac embolic sources were evaluated using TOE in 360 patients with fresh ischaemic stroke proven by diffusion-weighted MRI, including 210 patients with a single infarct and 150 with multiple infarcts, as well as in 101 non-stroke control patients. An ulcer was defined as a crater on the plaque ≥2.0 mm in depth and width. RESULTS: An ulcerated plaque was identified in 10.6% of patients with stroke versus 2.0% of non-stroke patients, showing a 5.11-fold higher frequency in patients with stroke (95% CI 1.51 to 31.96) after adjustment for age and sex. After multivariate adjustment for clinical and ultrasonographic features, multiple-infarct patients had a 7.61-fold higher risk (95% CI 1.99 to 50.43) of having an ulcer than control patients and a 3.32-fold higher risk (95% CI 1.61 to 7.18) of having an ulcer than single-infarct patients. Diabetes mellitus and drinking habit were independently related to the presence of ulcerated plaque in patients with stroke. CONCLUSIONS: Ulcerated plaque in the aortic arch was associated with the development of ischaemic stroke, especially multiple brain infarcts, probably involving, at least in part, an embolic mechanism.

Relationship between tongue pressure and dysphagia in stroke patients.

BACKGROUND: Although poststroke dysphagia is an important issue for determining prognosis, the pathophysiology of oral-phase dysphagia has yet to be clarified due to a lack of adequate devices and protocols. The present study investigated the relationships between swallowing pressure production by the tongue and dysphagia in stroke patients using a newly developed method of tongue pressure measurement with a sensor sheet system. METHODS: Subjects were 64 stroke patients, including 30 patients with dysphagia. A T-shaped sensor sheet with 5 measuring points was attached to the hard palate to record tongue pressure while swallowing 5 ml of water. The average maximal magnitude and incidence of abnormalities such as asynchronous and/or polyphasic patterns in tongue pressure waves in 5 locations were compared between patients with and without dysphagia. RESULTS: The average maximal tongue pressure was significantly smaller in patients with dysphagia than in those without dysphagia. Asynchronous and polyphasic patterns showed a sensitivity of 63 and 87%, and a specificity of 91 and 71%, respectively, for identifying patients with dysphagia. CONCLUSION: Tongue pressure production during swallowing appears closely related to poststroke dysphagia. Tongue pressure measurement appears useful for evaluating the pathophysiology of oral-phase dysphagia in stroke patients.

Atheromatous plaques at the origin of the left subclavian artery in patients with ischemic stroke.

BACKGROUND: Atheromatous plaques of the aortic arch that extend to the origin of its branches may cause stroke. The frequency and clinical implications of plaque at the origin of the left subclavian artery (LSCA) in patients with recent ischemic stroke were investigated. METHODS: We studied 347 consecutive patients (223 men, 69 +/- 12 years) who developed symptomatic ischemic stroke and underwent transesophageal echocardiography (TEE). RESULTS: The origin of the LSCA was identified in 303 of 347 patients (87.3%). Plaque > or =1.0 mm was detected in 108 of the 303 patients (35.6%), ranging between 1.0 and 6.1 mm (median, 2.5 mm). Patients having thicker plaque (> or =2.5 mm) were older (p = 0.012) and more commonly took antiplatelets prior to stroke (p = 0.038) than patients with no plaque and those with thinner plaque (<2.5 mm). Of the aortic arch findings detected on TEE, maximum intima-media thickness (IMT) was the highest (p < 0.001) in patients with thicker plaque, and large plaque (> or =4.0 mm) (p = 0.017), ulcerative plaques (p < 0.001), and spontaneous echo contrasts (p = 0.001) were identified most commonly in patients with thicker plaque. The frequency of infarcts involving the posterior circulation was similar among the three groups. After multivariate adjustment, maximum IMT of the aortic arch was independently related to thicker plaque at the LSCA origin (OR = 1.24, 95% CI = 1.03-1.51, p = 0.024, per 1-mm increase). CONCLUSIONS: Atheromatous plaque at the origin of the LSCA was present in approximately one third of patients with a recent ischemic stroke. High IMT at the aortic arch was independently related to the presence of thick plaque at the LSCA origin. The present study does not support the concept that plaque at the LSCA origin may be associated with posterior circulation infarction.

Severe hyperthermia caused by four-vessel occlusion of main cerebral arteries.

We present the case of a comatose patient with acute large infarction of posterior cerebral and cerebellar areas and severe hyperthermia (max. 40.4 degrees C). Angiography demonstrated four-vessel occlusion of the main cerebral arteries, suggesting the possibility that both internal carotid and left vertebral arteries were already occluded and he became unconscious following additional occlusion of the right vertebral artery. Autopsy findings revealed bilateral ischemic damage of the hypothalamus in addition to the above infarct areas. Sudden ischemic involvement of both hypothalamic regions may have caused the extremely high fever in this case.

Changes in diffusion-weighted magnetic resonance imaging findings in the acute and subacute phases of anoxic encephalopathy.

We report serial magnetic resonance imaging findings in a case of anoxic encephalopathy (AE). Diffusion-weighted images clearly showed early development of lesions in the cerebellum, cerebral cortex, and caudate putamen, along with delayed manifestation of lesions in the hippocampus, corpus callosum, and white matter. The present case is the first to demonstrate delayed development of postischemic changes in the hippocampus and deep white matter after AE on neuroimaging.

Paradoxical cerebral embolism causing internal carotid artery occlusion.

Paradoxical cerebral embolism (PCE) is defined to be a pathological condition in which emboli originating from the venous system reach the cerebral arterial circulation via the right-to-left (R-L) shunt. In patients with PCE, emboli originating from the venous system most commonly pass through the patent foramen ovale during Valsalva-provoking activities which increase the right atrial pressure above the left atrial pressure. The size of cerebral infarction caused by PCE is generally small, since the size of emboli which can pass through the R-L shunt is small. Here, we report a case of PCE which occluded the internal carotid artery (ICA).

Ischemic vasoconstriction and tissue energy metabolism during global cerebral ischemia in gerbils.

Vasoconstriction is known to occur in cerebral arterioles during ischemia and considered to be distinct from vasospasm seen after subarachnoid hemorrhage. To elucidate the mechanism and functional significance underlying ischemic vasoconstriction, we investigated the relationship between arteriolar constriction and tissue energy metabolism during bilateral common carotid artery occlusion in gerbils. Using video microscopy and microspectroscopy, the arteriolar caliber, the total hemoglobin (Hb) content, and the redox state of cytochrome oxidase (cyt.aa3) were monitored in the cerebral cortex in vivo. After in situ freezing of the brain, adenine nucleotides, creatine phosphate (P-Cr), and lactate levels were analyzed using high-performance liquid chromatography in vitro. Tissue damage was also assessed immunohistochemically using antibodies against microtubule-associated proteins. There was a slight reduction of the diameter of pial arterioles during the initial 1 min of ischemia. A rapid decline of total Hb and reduction of cyt.aa3 were observed with rapid decreases of P-Cr and ATP in the cortical tissue during the initial 0.5 min, but all of them showed tendencies to return toward preischemic levels at 0.5-1 min. Beyond 1.5 min, extensive vasoconstriction occurred together with further decline of total Hb, reduction of cyt.aa3, and decreases of ATP and P-Cr. Neuronal damage developed in the cerebral cortex immunohistochemically beyond 3 min. The present investigation demonstrated two phases of vasoconstriction with the possibilities that the immediate vasoconstriction likely contributed to transient improvement of cortical oxygen/energy metabolism, and the second extensive vasoconstriction was an index of tissue energy failure and imminent neuronal damage.

N-acetylaspartate to total creatine ratio in the hippocampal CA1 sector after transient cerebral ischemia in gerbils: influence of neuronal elements, reactive gliosis, and tissue atrophy.

The authors compared temporal profiles of N-acetylaspartate (NAA) and the NAA/total creatine ratio with neuronal and astrocytic densities and with tissue atrophy in the hippocampal CA1 sector of gerbils after 5-minute bilateral forebrain ischemia and subsequent reperfusion for up to 6 months. The CA1 sector was dissected from 20- micro m lyophilized sections (n = 5) for NAA, phosphocreatine, and creatine assays using high-performance liquid chromatography. Adjacent 10- micro m sections were used for immunohistochemical analysis to follow neuronal and astrocytic responses. The NAA concentration was significantly (P<0.01) decreased after 7 days but leveled off thereafter. The NAA/total creatine (phosphocreatine + creatine) ratio was significantly decreased after 7 days and further decreased (P<0.05) after 6 months. Extensive neuronal damage developed beyond 7 days, while reactive astrogliosis progressed throughout the observation period. There was a good linear correlation (P<0.01) between astroglial density and the NAA/total creatine ratio beyond 7 days. The thickness of the CA1 sector was significantly reduced after 1 month and further reduced after 6 months. Although both NAA level and the NAA/total creatine ratio seemed to be indicators of neuronal damage, the latter could be influenced by reactive astrogliosis with progression of tissue atrophy.