New Artificial Intelligence-Integrated Electromyography-Driven Robot Hand for Upper Extremity Rehabilitation of Patients With Stroke: A Randomized, Controlled Trial.

BACKGROUND: An artificial intelligence (AI)-integrated electromyography (EMG)-driven robot hand was devised for upper extremity (UE) rehabilitation. This robot detects patients' intentions to perform finger extension and flexion based on the EMG activities of 3 forearm muscles. OBJECTIVE: This study aimed to assess the effect of this robot in patients with chronic stroke. METHODS: This was a single-blinded, randomized, controlled trial with a 4-week follow-up period. Twenty patients were assigned to the active (n = 11) and control (n = 9) groups. Patients in the active group received 40 minutes of active finger training with this robot twice a week for 4 weeks. Patients in the control group received passive finger training with the same robot. The Fugl-Meyer assessment of UE motor function (FMA), motor activity log-14 amount of use score (MAL-14 AOU), modified Ashworth scale (MAS), H reflex, and reciprocal inhibition were assessed before, post, and post-4 weeks (post-4w) of intervention. RESULTS: FMA was significantly improved at both post (P = .011) and post-4w (P = .021) in the active group. The control group did not show significant improvement in FMA at the post. MAL-14 AOU was improved at the post in the active group (P = .03). In the active group, there were significant improvements in wrist MAS at post (P = .024) and post-4w (P = .026). CONCLUSIONS: The AI-integrated EMG-driven robot improved UE motor function and spasticity, which persisted for 4 weeks. This robot hand might be useful for UE rehabilitation of patients with stroke.Clinical Trial Registry Name: The effect of robotic rehabilitation using XMM-HR2 for the paretic upper extremity among hemiparetic patients with stroke.Clinical Trial Registration-URL: https://jrct.niph.go.jp/Unique Identifier: jRCTs032200045.

Factor analysis for construct validity of a trunk impairment scale in Parkinson's disease: a cross-sectional study.

Objectives: To investigate the construct validity of the Trunk Impairment Scale (TIS), which was developed to assess trunk impairment in patients with stroke, in patients with Parkinson's disease (PD). Design: This retrospective, cross-sectional study enrolled consecutive PD inpatients. Correlation analysis was performed to clarify whether the TIS assessment was related to other balance functions, lower extremity muscle strength, or walking ability. Factor analysis was performed to see how the background factors of TIS differ from balance function, lower limb muscle strength, and walking ability. Results: Examining the data of 471 patients with PD, there were relationships between TIS and the Mini-Balance Evaluation Systems Test (r = 0.67), Barthel Index (r = 0.57), general lower limb extension torque (r = 0.51), two-minute walk test (r = 0.54), Hoehn and Yahr stage (r = -0.61), and Movement Disorder Society Unified Parkinson's Disease Rating Scale part III total points (r = -0.59). Factor analysis showed that TIS items were divided into three factors (an abdominal muscles and righting reflex component; a perception and verticality component; and a rotational component), differing from other scales that included clinical assessment items. Conclusion: The TIS can be useful for assessing the underlying trunk impairment as a basis for activities of daily living, gait function, and balance ability in patients with PD.

Prediction of gait independence using the Trunk Impairment Scale in patients with acute stroke.

Background: Gait recovery is one of the primary goals of stroke rehabilitation. Gait independence is a key functional component of independent activities in daily living and social participation. Therefore, early prediction of gait independence is essential for stroke rehabilitation. Trunk function is important for recovery of gait, balance, and lower extremity function. The Trunk Impairment Scale (TIS) was developed to assess trunk impairment in patients with stroke. Objective: To evaluate the predictive validity of the TIS for gait independence in patients with acute stroke. Methods: A total of 102 patients with acute stroke participated in this study. Every participant was assessed using the TIS, Stroke Impairment Assessment Set (SIAS), and Functional Independence Measure (FIM) within 48 h of stroke onset and at discharge. Gait independence was defined as FIM gait scores of 6 and 7. Multiple regression analysis was used to predict the FIM gait score, and multiple logistic regression analysis was used to predict gait independence. Cut-off values were determined using receiver operating characteristic (ROC) curves for variables considered significant in the multiple logistic regression analysis. In addition, the area under the curve (AUC), sensitivity, and specificity were calculated. Results: For the prediction of the FIM gait score at discharge, the TIS at admission showed a good-fitting adjusted coefficient of determination (R 2 = 0.672, p < 0.001). The TIS and age were selected as predictors of gait independence. The ROC curve had a TIS cut-off value of 12 points (sensitivity: 81.4%, specificity: 79.7%) and an AUC of 0.911. The cut-off value for age was 75 years (sensitivity: 74.6%, specificity: 65.1%), and the AUC was 0.709. Conclusion: The TIS is a useful early predictor of gait ability in patients with acute stroke.

A phase I/IIa trial of atorvastatin in Japanese patients with acute Kawasaki disease with coronary artery aneurysm: Study protocol of a multicenter, single-arm, open-label trial.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis complicated with coronary artery abnormalities (CAAs). Intravenous immunoglobulin reduces the occurrence of CAAs, but significant number of KD patients with CAAs still exists. Thus, new approaches to prevent and attenuate CAAs are warranted. Atorvastatin has been shown to promote endothelial cell homeostasis and suppress vascular inflammation and has received enthusiasm as a potentially new candidate treatment for KD. In the United States, a phase I/IIa dose-escalation study of atorvastatin in KD patients with CAAs demonstrated the safety and pharmacokinetic data of atorvastatin. However, due to the uncertainty in the application of these results to other populations, we aim to examine the tolerability and generate pharmacokinetics data in Japanese KD patients. METHODS: This is a multicenter, single-arm, open-label, phase I/IIa study of atorvastatin in acute KD patients with CAAs in Japan. A minimum of 9 and a maximum of 18 KD patients (2 years-17 years old) will be recruited for a 3 + 3 dose-escalation study of a 6-week course of atorvastatin (0.125-0.5 mg/kg/day). The primary outcome will be safety of atorvastatin. The secondary outcomes will be pharmacokinetics of atorvastatin, activity of atorvastatin and echocardiographic assessment of CAAs. The activity of atorvastatin will include assessment of C-reactive protein or high sensitivity C-reactive protein and white blood cell levels. DISCUSSION: This study will provide evidence of the safety, tolerability, and pharmacokinetics of atorvastatin in Japanese KD patients and may lead new standard therapy for acute-phase KD associated with CAA complications. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCTs031180057). Registered December 19, 2018, https://jrct.niph.go.jp/en-latest-detail/jRCTs031180057.

Learning from Goal and Action Based Observations Differentially Modulates Functional Motor Cortical Plasticity.

Action observation can facilitate motor skill learning and lead to a memory trace in motor representations of action. However, it remains unclear whether the action itself or the goal of the action drive changes in motor representations after learning by observation. We performed two experiments. In Experiment 1, using serial reaction time task and transcranial magnetic stimulation, we showed that observation of right-hand actions during skill learning only increased left motor cortical excitability, leading to behavioral gains in the same hand as the observed hand. In contrast, observing a sequence of visual cue positions devoid of hand action increases motor cortical excitability in both hemispheres and facilitates motor skill learning in the right hand (Experiment 1) and left hand for a mirror-symmetric sequence (Experiment 2). We propose that the encoding of observed movements maps onto motor representations of the same action to form a limb-specific motor memory, whereas the learning of spatial goals forms memory traces in the motor representations in both hemispheres to prepare for potential action in either hand.

Rubber hand illusion modulates the influences of somatosensory and parietal inputs to the motor cortex.

The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually occluded hand. It involves visual, tactile, and proprioceptive multisensory integration and activates multisensory areas in the brain, including the posterior parietal cortex (PPC). Multisensory inputs are transformed into outputs for motor control in association areas such as PPC. A behavioral study reported decreased motor performance after RHI. However, it remains unclear whether RHI modifies the interactions between sensory and motor systems and between PPC and the primary motor cortex (M1). We used transcranial magnetic stimulation (TMS) and examined the functional connections from the primary somatosensory and association cortices to M1 and from PPC to M1 during RHI. In experiment 1, short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were measured before and immediately after a synchronous (RHI) or an asynchronous (control) condition. In experiment 2, PPC-M1 interaction was measured using two coils. We found that SAI and LAI were reduced in the synchronous condition compared with baseline, suggesting that RHI decreased somatosensory processing in the primary sensory and the association cortices projecting to M1. We also found that greater inhibitory PPC-M1 interaction was associated with stronger RHI assessed by questionnaire. Our findings suggest that RHI modulates both the early and late stages of processing of tactile afferent, which leads to altered M1 excitability by reducing the gain of somatosensory afferents to resolve conflicts among multisensory inputs. NEW & NOTEWORTHY Perception of one's own body parts involves integrating different sensory information and is important for motor control. We found decreased effects of cutaneous stimulation on motor cortical excitability during rubber hand illusion (RHI), which may reflect decreased gain of tactile input to resolve multisensory conflicts. RHI strength correlated with the degree of inhibitory posterior parietal cortex-motor cortex interaction, indicating that parietal-motor connection is involved in resolving sensory conflicts and body ownership during RHI.

Functional interaction between human dorsal premotor cortex and the ipsilateral primary motor cortex for grasp plans: a dual-site TMS study.

Recent findings suggest that the dorsal premotor cortex (PMd), a cortical area in the dorsomedial pathway, is involved in grasp control. It is unclear, however, whether human PMd transfers grasp-related information to the primary motor cortex hand area (M1HAND) during action preparation. The present study tested whether ipsilateral cortico-cortical connections between PMd and M1HAND in the left hemisphere are modulated during grasp preparation. Ten participants performed object-directed grasps and reaches with the right hand. Functional connectivity between left PMd and ipsilateral M1HAND was probed with dual-site transcranial magnetic stimulation. We found that PMd-M1HAND functional interactions were facilitated selectively for the muscles involved in the preparation of the upcoming grasps. The PMd-M1HAND interaction was facilitated for first dorsal interosseous muscle for both precision grip and whole-hand grasps and for abductor digiti minimi muscle for whole-hand grasps. We conclude that human dorsomedial PMd-M1HAND circuit encodes handgrip formation during grasp preparation.

Increases in motor cortical excitability during mirror visual feedback of a precision grasp is influenced by vision and movement of the opposite limb.

Unimanual grasp movements with mirrored visual feedback (MVF) can improve function and increase excitability of primary motor cortex (M1) ipsilateral to the moving hand. However, no study to date has examined the contribution of vision and movement of the opposite hand during an object-directed precision grasp. In this study, we tested 15 healthy individuals in three conditions: MVF (vision + motor), Movement (motor component), and Action Observation (vision component). We hypothesized that unimanual grasp movements with MVF increases the excitability and reduces intracortical inhibition of the M1 ipsilateral to the moving hand. We found increased excitability in the right primary motor cortex (M1) ipsilateral to the moving right hand for MVF movements compared to Rest (Baseline). In contrast, no change was found in right M1 with only movement of the right hand or observation of object-directed precision grasp with left hand. We also found a reduction in short-interval intracortical inhibition in MVF movements compared to baseline. These findings suggest that excitability in M1 during an object-directed precision grasp is mediated by the combination of viewing the movement performed and performing the movement from the opposite hand.

Human dorsomedial parieto-motor circuit specifies grasp during the planning of goal-directed hand actions.

According to one influential view, two specialized parieto-frontal circuits control prehension: a dorsomedial stream for hand transport during reaching and a dorsolateral stream for preshaping the fingers during grasping. However, recent evidence argues that an area within the dorsomedial stream-macaque area V6A and, its putative human homolog, superior parietal occipital cortex (SPOC) - encodes both hand transport and grip formation. We tested whether planning varied hand actions modulates functional connectivity between left SPOC and ipsilateral primary motor cortex (M1) using a dual-site, paired-pulse transcranial magnetic stimulation paradigm with two coils (dsTMS). Participants performed three different hand actions to a target object comprising a small cylinder atop a larger cylinder. These actions were: reaching-to-grasp the top (GT) using a precision grip, reaching-to-grasp the bottom (GB) using a whole-hand grip, or reaching-to-touch (Touch) the side of the target object without forming a grip. Motor-evoked potentials (MEPs) from TMS to M1, with or without preceding TMS to SPOC, were recorded from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) hand muscles in two experiments that varied timing parameters (the stimulus onset asynchrony, SOA, between the 'GO' cue and stimulation and interpulse interval, IPI, between SPOC and M1 stimulation). We found that preparatory response amplitudes in the SPOC-M1 circuit of different hand muscles were selectively modulated early in the motor plan for different types of grasps. First, based on SPOC-M1 interactions, across two experiments, the role of the ADM was facilitated during a whole-hand grasp of a large object (GB) relative to other conditions under certain timing parameters (SOA = 150 msec; IPI = 6 msec). Second, the role of the FDI was facilitated during hand action planning compared to rest. These findings suggest that the human dorsomedial parieto-motor stream plays a causal role in planning grip formation for object-directed actions.

The long-term outcome of orthostatic tremor.

OBJECTIVES: Orthostatic tremor is a rare condition characterised by high-frequency tremor that appears on standing. Although the essential clinical features of orthostatic tremor are well established, little is known about the natural progression of the disorder. We report the long-term outcome based on the largest multicentre cohort of patients with orthostatic tremor. METHODS: Clinical information of 68 patients with clinical and electrophysiological diagnosis of orthostatic tremor and a minimum follow-up of 5 years is presented. RESULTS: There was a clear female preponderance (76.5%) with a mean age of onset at 54 years. Median follow-up was 6 years (range 5-25). On diagnosis, 86.8% of patients presented with isolated orthostatic tremor and 13.2% had additional neurological features. At follow-up, seven patients who initially had isolated orthostatic tremor later developed further neurological signs. A total 79.4% of patients reported worsening of orthostatic tremor symptoms. These patients had significantly longer symptom duration than those without reported worsening (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in orthostatic tremor frequency over time. Structural imaging was largely unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases. Pharmacological treatments were disappointing. Two patients were treated surgically and showed improvement. CONCLUSIONS: Orthostatic tremor is a progressive disorder with increased disability although tremor frequency is unchanged over time. In most cases, orthostatic tremor represents an isolated syndrome. Drug treatments are unsatisfactory but surgery may hold promise.

The influence of sensory afferent input on local motor cortical excitatory circuitry in humans.

In human, sensorimotor integration can be investigated by combining sensory input and transcranial magnetic stimulation (TMS). Short latency afferent inhibition (SAI) refers to motor cortical inhibition 20-25 ms after median nerve stimulation. We investigated the interaction between SAI and short-interval intracortical facilitation (SICF), an excitatory motor cortical circuit. Seven experiments were performed. Contrary to expectations, SICF was facilitated in the presence of SAI (SICF(SAI)). This effect is specific to SICF since there was no effect at SICF trough 1 when SICF was absent. Furthermore, the facilitatory SICF(SAI) interaction increased with stronger SICF or SAI. SAI and SICF correlated between individuals, and this relationship was maintained when SICF was delivered in the presence of SAI, suggesting an intrinsic relationship between SAI and SICF in sensorimotor integration. The interaction was present at rest and during muscle contraction, had a broad degree of somatotopic influence and was present in different interneuronal SICF circuits induced by posterior-anterior and anterior-posterior current directions. Our results are compatible with the finding that projections from sensory to motor cortex terminate in both superficial layers where late indirect (I-) waves are thought to originate, as well as deeper layers with more direct effect on pyramidal output. This interaction is likely to be relevant to sensorimotor integration and motor control.

Reduced dorsal premotor cortex and primary motor cortex connectivity in older adults.

Motor functions decline with increasing age. The underlying mechanisms are still unclear and are likely to be multifactorial. There is evidence for disruption of white matter integrity with age, which affects cortico-cortical connectivity. Studies with transcranial magnetic stimulation found both inhibitory and facilitatory connections from dorsal premotor cortex (PMd) to the ipsilateral primary motor cortex (M1) in young adults. We investigated whether aging affects this connectivity in 15 older and 15 young healthy adults. Transcranial magnetic stimulation in a paired-pulse paradigm was used to test the connectivity between left PMd and M1. Motor evoked potential in the right first dorsal interosseous muscle was recorded. We found that both the inhibitory effect with low intensity PMd stimulation and the facilitatory effect with high intensity PMd stimulation observed in young adults were decreased in older adults. We conclude that the connectivity between PMd and ipsilateral M1 is reduced in older adults.

Sixty six-month follow-up of muscle power and respiratory function in a case with adult-type Pompe disease treated with enzyme replacement therapy.

We report a patient with adult-type Pompe disease treated with enzyme replacement therapy (ERT) for 5.5 years. We evaluated pulmonary function and muscle strength using 6-minute walk test, manual muscle test, and dynamometer-based measurement. The long-term ERT resulted in a substantial improvement in the pulmonary function and a possible stabilization followed by mild deterioration in muscle power measured by dynamometer and 6-minute walk test. Our data may rationalize the long-term use of ERT for adult-type Pompe disease in terms of maintaining pulmonary function.

Chronic inflammatory demyelinating polyneuropathy due to the administration of pegylated interferon α-2b: a neuropathology case report.

We report a 35-year-old man who developed weakness in his extremities five months after pegylated interferon α (IFNα)-2b was administered. The serum tumor necrosis factor-α (TNFα) was elevated and nerve conduction studies revealed demyelination both in the distal and intermediate segments. The sural nerve pathology showed mild demyelinating process. The cessation of IFNα and administration of intravenous immunoglobulin improved both his clinical symptoms and the temporal dispersion in motor nerve conduction study. IFNα-induced CIDP is presumably a transient immunological condition that requires immunomodulatory therapy. The elevated serum TNFα may implicate the degree of downstream autoimmunity induced by IFNα.

[A case of noninvasive sinus aspergillosis showing orbital apex syndrome].

A 78-year-old man was admitted to our hospital with headache, nasal pain, left-sided ptosis, loss of visual field in his left eye, and left ophthalmoplegia. Serum levels of beta-D-glucan were elevated. T1-weighted magnetic resonance imaging with gadolinium enhancement showed hyperintense lesions in the left orbital apex and dura mater of the left middle cranial fossa. A few days later, culture of specimens collected by surgical debridement from the left sphenoidal sinus revealed numerous branching hyphae. The aspergillus antigen was found in the cerebrospinal fluid (CSF). Therefore, aspergillosis causing orbital apex syndrome was diagnosed. Administration of amphotericin B prevented further worsening of the patient's infection. Although noninvasive sinus aspergillosis showed that fungus did not destroy tissues in general, the condition resulted in intracranial impairments observed in this case, including orbital apex syndrome and hypertrophic pachymeningitis. Furthermore, detection of the aspergillus antigen in CSF was a clue for the diagnosis of aspergillosis, and administration of antifungal drugs in the early stages of infection was an effective treatment

[A rare complication of dysarthria in a patient with inclusion body myositis: a case report].

We reported a 71-year-old man with inclusion body myositis with clinically overt dysarthria. He had been suffering from gradual progression of weakness in the hand muscles and lower extremities as well as dysarthria three years before admission. His neurological examination revealed muscle atrophy and weakness in the tongue, the forearm flexors, and the vastus medialis muscles. He had dysarthria to a moderate degree, while he denied any dysphasia. A biopsy from vastus lateralis muscle showed variation in fiber size, infiltration of mononucleated cells, and numerous fibers with rimmed vacuoles, leading to the diagnosis of definite inclusion body myositis. The EMG findings of the tongue demonstrated low amplitude motor unit potentials during voluntary contraction, abundant fibrillation potentials at rest, and preserved interference pattern at maximal contraction, implying myogenic changes. We surmised the dysarthria seen in this patient, an atypical clinical feature in IBM, presumably caused by muscle involvement in the tongue muscle. Dysphasia is common symptom in IBM patient and has been much reported previously. But dysarthria in IBM patient has not been aware, for this reason this report should be the rare case.

Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine.

A 64-year-old woman was admitted to our hospital for recurrent stroke and cognitive impairment and was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Iodine-123 iodoamphetamine single photon emission computed tomography showed hypoperfusion in the whole brain, but cerebral blood flow increased dramatically after the administration of acetazolamide in the cerebral cortex. Lomerizine, a diphenylmethylpiperazine Ca2+ channel blocker, can selectively increase cerebral blood flow. Cognitive decline and cerebral hypoperfusion improved during 2-year administration of lomerizine in this CADASIL patient, and thus, lomerizine is a potential candidate for treating cognitive impairment in CADASIL patients.