Takayo Chuma

Repetitive Transcranial Magnetic Stimulation of Contralesional Primary Motor Cortex Improves Hand Function After Stroke

Background and Purpose— A recent report has demonstrated that the contralesional primary motor cortex (M1) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition (TCI) in stroke patients. We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation (rTMS) caused an improved motor performance of the affected hand in stroke patients by releasing the TCI. Methods— We conducted a double-blind study of real versus sham rTMS in stroke patients. After patients had well- performed motor training to minimize the possibility of motor training during the motor measurement, they were randomly assigned to receive a subthreshold rTMS at the contralesional M1 (1 Hz, 25 minutes) or sham stimulation. Results— When compared with sham stimulation, rTMS reduced the amplitude of motor-evoked potentials in contralesional M1 and the TCI duration, and rTMS immediately induced an improvement in pinch acceleration of the affected hand, although a plateau in motor performance had been reached by the previous motor training. This improvement in motor function after rTMS was significantly correlated with a reduced TCI duration. Conclusions— We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected hand in stroke patients; this suggests a new neurorehabilitative strategy for stroke patients.

Motor learning of hands with auditory cue in patients with Parkinson’s disease

Summary.In the present research, changes in motor cortex function were observed in relation to repetitive, voluntary thumb movement (training) in patients with Parkinson’s disease (PD) and normal control subjects. Changes in the direction of thumb movement due to motor evoked potential (MEP) by transcranial magnetic stimulation (TMS), after motor training with and without rhythmic sound, were measured using a strain gauge for 12 patients with PD and 9 normal control subjects. PD patients who experienced the freezing phenomena showed poor change in direction of TMS-induced movement after self-paced movement; however, marked change in direction of TMS-induced movement was observed after training with auditory cue. PD patients who had not experienced the freezing phenomena showed positive effects with the auditory cue, producing similar results as the normal control subjects. Two routes for voluntary movement are available in the nervous system. The decreased function of basal ganglia due to PD impaired the route from the basal ganglia to the supplementary motor cortex. These data suggest that the route from sensory input to cerebellum to premotor cortex could compensate for the decreased function of the route via the basal ganglia to the premotor cortex. Once change in the motor cortex occurred, such change persisted even after the interruption of training. These phenomena suggest that motor memory can be stored in the motor cortex.

Dysferlinopathy associated with rigid spine syndrome

Dysferlinopathy and rigid spine syndrome occurring in a 50‐year‐old man is reported. The patient noticed stiffness of knee and ankle joints, which gradually extended to neck, wrist and elbow joints leading to difficulty in anterior flexion. Muscular weakness and wasting of the lower extremities  had  developed  since  age  40,  accompanied  by  a limitation of anterior bending of the spine. Elevated serum CK was noticed. Muscle CT revealed atrophy with moderate fatty replacement of muscles in the neck, shoulder and pelvic girdle, and marked replacement in the para‐vertebral muscles, posterior compartment of hamstrings and calf muscles. Electromyography showed a typical myogenic pattern, and muscle biopsy disclosed dystrophic changes, compatible with limb‐girdle muscular dystrophy 2B. Loss of dysferlin expression was verified by immunohistochemistry, which was confirmed by a mini‐multiplex Western blotting system. Gene analyses of the dysferlin gene disclosed compound heterozygotes for frameshift (G3016 + 1A) and a missense mutation (G3370T). This study might propose some clues to resolve the combination of musular dystrophies and rigid spine syndrome.

Disinhibition of the Premotor Cortex Contributes to a Maladaptive Change in the Affected Hand After Stroke

Background and Purpose— The mechanism of reorganization after stroke remains uncertain. Several studies that have measured reaction time (RT) delay by transcranial magnetic stimulation (TMS) have revealed some substrates responsible for the reorganization of motor recovery. In this study, we evaluated the RT delay and inhibitory functions by examining the silent period (SP) in the primary motor cortex (M1) and premotor cortex (PMC) of the affected hemisphere. Using these data, we investigated whether a change in the inhibitory system might influence motor recovery. Methods— This study was performed in 20 patients with chronic subcortical stroke. To evaluate the RT delay, TMS was applied to the affected hemisphere 100 ms after showing the cue that indicated paretic finger movement. The SP was induced by TMS over the affected hemisphere during voluntary contraction of the paretic hand. Results— The RT delays of the PMC were more prominent in patients with greater disability. The ratio of SP duration to RT delay in the PMC decreased with the decline in motor function. Moreover, upper arm function was better than hand function in patients with a decreased SP in the PMC. Conclusions— The inhibitory function of the PMC was disturbed in patients with poor motor function. Stroke patients with poor motor ability appeared to depend not only on the motor pathway from M1 but also on other parallel motor circuits to move the paretic side. However, this brain reorganization might result in the sacrifice of function of the affected hand.

Clinicopathological studies of peripheral neuropathy in Churg-Strauss syndrome.

Clinicopathological studies were performed on the visceral organs and the sural nerve of a male patient with Churg–Strauss syndrome (CSS) in order to understand the mechanisms of peripheral nervous system damage. A 67‐year‐old man, with a 2‐year history of bronchial asthma, developed acutely painful paraplegia and dyspnea. Laboratory data showed a leukocytosis, an elevated serum creatinine kinase (CK) and marked eosionophilia. Autoantibodies including p‐ and c‐ANCA were negative. Electrophysiological studies revealed a severe sensory‐motor neuropathy of multiple mononeuritis type. Steroid pulse therapy performed a day after biopsy of skin, muscle and sural nerve was effective in resolving his respiratory and neurological dysfunction but a perforation of an intestinal ulcer occurred which required surgical intervention. In the biopsied sural nerve and the surgically resected intestine and mesentery there was vasculitis with fibrinoid necrosis accompanied by numerous eosinophils and macrophages containing eosinophil cationic protein (ECP). These findings suggest that in addition to ischemic changes due to vasculitis some neurotoxic substances generated by the eosinophils may be involved in the development of neuropathy in CSS.

Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG) 11 in PABP2 gene

Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.

Cortical reorganization in training

Plasticity within the human central motor system occurs and has been studied with transcranial magnetic stimulation in patients with amputations, spinal cord injuries, and ischemic nerve block. These studies have identified a pattern of motor system reorganization that results in enlarged muscle representation areas and large motor evoked potentials (MEPs) for muscles immediately proximal to the lesion. Some of these changes are apparent minutes after ischemic nerve block, weeks after spinal cord injury, and as early as six months after amputation.These studies motivated us to study the cortical motor reorganization after finger movement training in normals and after anastomosis of intercostal nerves to the musculocutaneous nerve in young patients with cervical root avulsions due to a traumatic motorcycle injury.

Measurement of transcallosal inhibition in traumatic brain injury by transcranial magnetic stimulation

Primary objective: To study whether transcallosal inhibition (TCI) can evaluate the severity of traumatic brain injury (TBI). Research design: Case-control study. Methods and procedures: Twenty patients with a chronic TBI and 20 control subjects were studied. The following transcranial magnetic stimulation parameters were checked; resting motor threshold, central motor latency times, onset latency of TCI, duration of TCI, transcallosal conduction times and amount of TCI. The severity of TBI was evaluated using the Glasgow Coma Scale (GCS). Main outcome and results: The amount of TCI was significantly lower in the patients than the control subjects (p < 0.001). The amount of TCI was highly correlated with the GCS (r = 0.787, p < 0.001). Conclusion: An assessment of TCI was found to be a more sensitive and useful method for an evaluation of the severity of TBI.

Chronic demyelinating polyneuropathy in graft‐versus‐host disease following allogeneic bone marrow transplantation

In recent years a novel problem has arisen in organ transplantation medicine, namely GVHD. The nervous system has been involved mainly at the level of the CNS and this can lead to a serious outcome for the patient. In rare cases, peripheral nerves may be affected and show acute or chronic polyneuropathy. Here a case is reported of polyneuropathy associated with chronic GVHD. A 32‐year‐old man, suffering from chronic GVHD following an allogeneic bone marrow transplantation (BMT) for malignant lymphoma at the age of 25, developed a motor dominant polyneuropathy 5 years later. Electrophysiologic studies demonstrated the demyelinating type of polyneuropathy. Biopsy specimens from skin and skeletal muscle disclosed perivascular lymphocytic infiltrates expressing T‐cell markers. The sural nerve showed a loss of myelinated nerve fibers with epineurial fibrosis and rare occurrence of T cells, but without obvious vasculitic changes. The present case suggested that polyneuropathy could develop in association with chronic GVHD in some patients with a longstanding disease course.

Clinicopathological and virological analyses of familial human T-lymphotropic virus type I–associated polyneuropathy

Human T-lymphotropic virus type I (HTLV-I) is known to be the causative agent of the chronic myelopathy, HTLV-I-associated myelopathy (HAM), and on rare occasions infection is also associated with the development of polyneuropathy. Here the authors present an HTLV-I-positive family of whom four members developed a chronic demyelinating polyneuropathy without HAM. Four female patients in a family from Hokkaido in Japan developed distal dominant paresthesia and muscle weakness in the second and third decades of their life. Neurological findings at ages ranging from 50 to 65 years included mild painful sensorimotor disturbances with atrophy of the distal parts of the extremities but without pyramidal signs or hyperactive tendon reflexes. Magnetic resonance imaging (MRI) findings of brain and spinal cord were unremarkable. Serum HTLV-I antibody levels were elevated at 1:8,192 to 1:32,768, whereas those in cerebrospinal fluid were low at 1:4 to 1:8. Electrophysiological studies revealed polyphasic compound muscle action potentials with denervation potentials on nerve conduction studies and neurogenic patterns by electromyography, which were consistent with signs of chronic motor dominant demyelinating polyneuropathy. Sural nerve biopsy showed decreased myelinated fibers, occurrence of globule formation, myelin ovoid and remyelinated fibers, and an infiltration of CD68-positive macrophages with occasional CD4-positive T cells in the nerve fascicles. The polyneuropathy was responsive to steroid therapy. Analyses of serological human leukocyte antigen (HLA) types indicated that none of the patients possessed a high-risk HLA type known to be associated with adult T-cell leukemia (ATL), whereas they did have high responsive alleles to HTLV-I env similar to that observed in HAM. Nucleotide sequence analysis of the HTLV-I tax region demonstrated the B subgroup in all patients. This study suggests that HTLV-I infection can result in the development of a familial form of polyneuropathy that is associated with distinct HLA class I alleles, which might possibly involve a distinct virus subtype.