Case report: Klinefelter syndrome may protect against the development of spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive motor neuron disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the androgen receptor (AR) gene. It is thought that the nuclear translocation of abnormal AR proteins following binding to testosterone triggers the onset of the disease. We report the case of a patient who had SBMA coincident with Klinefelter syndrome. He developed SBMA symptoms rapidly after receiving androgen replacement therapy for Klinefelter syndrome. No cases of coincident SBMA and Klinefelter syndrome have been reported, and if confirmed by further patients in future, that androgen hormones are strongly associated with the development and progression of SBMA in fact in humans.

Assessment of safety of self-controlled repetitive trans-vertebral magnetic stimulation.

OBJECTIVE: The aim of this study was to assess safety issues of self-controlled repetitive trans-vertebral magnetic stimulation (rTVMS) in humans. METHODS: We investigated effects of self-controlled rTVMS (≤20 Hz, ≤90% intensity) on vital signs and subjective sensations in 1690 trials of 30 healthy volunteers and 12 patients with spinal cord disorders. RESULTS: Healthy volunteers and the patients received 4595 ± 2345, and 4450 ± 2304 pulses in one day, respectively. No serious adverse events were observed in any participants, and only minor events were seen as follows. While blood pressure was unaffected in the patients, the diastolic blood pressure increased slightly after rTVMS in healthy volunteers. The peripheral capillary oxygen saturation increased after rTVMS in healthy volunteers. "Pain" or "Discomfort" was reported in approximately 10% of trials in both participants groups. Degree of the evoked sensation positively correlated with stimulus intensity and was affected by the site of stimulation. CONCLUSION: Self-controlled rTVMS (≤20 Hz and ≤90% intensity) did not induce any serious adverse effects in healthy volunteers and patients with spinal cord disorders. SIGNIFICANCE: Our results indicate that rTVMS can be used safely in physiological investigations in healthy volunteers and also as treatment for neurological disorders.

A possible role of low regulatory T cells in anti-acetylcholine receptor antibody positive myasthenia gravis after bone marrow transplantation.

BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. CASE PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months. He showed progressive decrement of compound muscle action potential in the deltoid muscle evoked by 3-Hz repetitive nerve stimulation, a positive edrophonium test, and elevated levels of serum anti-acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG. No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes). Administration of prednisolone and tacrolimus was insufficient to alleviate his symptoms; however, the use of rituximab successfully improved his condition. CONCLUSIONS: Myasthenic symptoms appeared in the process of tapering prednisolone for the treatment of chronic GVHD, supporting the diagnosis of MG associated with chronic GVHD. The present case proposes a possibility that reduction of Tregs might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy with rituximab is beneficial for treatment of refractory MG and GVHD.

Variability in Response to Quadripulse Stimulation of the Motor Cortex.

BACKGROUND: Responses to plasticity-inducing brain stimulation protocols are highly variable. However, no data are available concerning the variability of responses to quadripulse stimulation (QPS). OBJECTIVE: We assessed the QPS parameters of motor cortical plasticity induction in a systematic manner, and later investigated the variability of QPS using optimal parameters. METHODS: First, two different interburst intervals (IBI) with the same total number of pulses were compared. Next we investigated three different IBIs with a different total number of pulses but with same duration of intervention. We also compared the after-effects of monophasic and biphasic QPS. Finally, variability of QPS was tested in 35 healthy subjects. Twenty motor evoked potentials (MEPs) were measured every 5-10 min for up to one hour after intervention. RESULTS: QPS at an IBI of 5 s produced MEPs changes that are dependent on the interstimulus interval of the four magnetic pulses, consistent with previous reports. Unexpectedly, QPS at an IBI of 2.5 s did not induce any plasticity, even with the same total number of pulses, that is, 1440. QPS at an IBI of 7.5 s produced a variable response but was likely to be comparable to conventional QPS. Biphasic QPS had shorter lasting after-effects compared with monophasic QPS. Finally, the after-effects of QPS were relatively consistent across subjects: more than 80% of subjects responded as expected in the excitatory QPS at an IBI of 5 s. CONCLUSIONS: The IBI, total duration of the procedure and pulse waveform strongly affected the magnitude or duration of the plasticity induced by QPS. In this cohort, 80% of subjects responded to excitatory QPS as expected.

Effects of 1950 MHz W-CDMA-like signal on human spermatozoa.

There are growing concerns about how electromagnetic waves (EMW) emitted from mobile phones affect human spermatozoa. Several experiments have suggested harmful effects of EMW on human sperm quality, motility, velocity, or the deoxyribonucleic acid (DNA) of spermatozoa. In this study, we analyzed the effects on human spermatozoa (sperm motility and kinetic variables) induced by 1 h of exposure to 1950 MHz Wideband Code Division Multiple Access (W-CDMA)-like EMW with specific absorption rates of either 2.0 or 6.0 W/kg, using a computer-assisted sperm analyzer system. We also measured the percentage of 8-hydroxy-2'-deoxyguanosine (8-OHdG) positive spermatozoa with flow cytometry to evaluate damage to DNA. No significant differences were observed between the EMW exposure and the sham exposure in sperm motility, kinetic variables, or 8-OHdG levels. We conclude that W-CDMA-like exposure for 1 h under temperature-controlled conditions has no detectable effect on normal human spermatozoa. Differences in exposure conditions, humidity, temperature control, baseline sperm characteristics, and age of donors may explain inconsistency of our results with several previous studies. Bioelectromagnetics. 37:373-381, 2016. © 2016 Wiley Periodicals, Inc.

Influence of phasic muscle contraction upon the quadripulse stimulation (QPS) aftereffects.

OBJECTIVE: Contractions of the target muscle influence the aftereffects of repetitive transcranial magnetic stimulation (rTMS). The aim of this paper is to investigate whether or not voluntary hand movement influences the aftereffects of quadripulse stimulation (QPS) on the hand motor area. METHODS: Thirteen healthy volunteers participated in this study. After QPS-5 or QPS-50 intervention over the motor hot spot for the right first dorsal interosseous muscle (FDI), the subjects performed voluntary motor tasks (opening-closing right hand movements at 1 Hz for 1 min). We compared the time courses of MEP size between the conditions with and without voluntary movement. RESULTS: When the subjects moved their hands immediately after QPS, both QPS-5 and QPS-50 aftereffects were abolished. However, if they moved their hands at 20 min after QPS, the long-term aftereffects were preserved. CONCLUSIONS: Voluntary hand movement applied after intervention influences QPS aftereffects, but the magnitude of the influence depends on the delay between QPS and the voluntary movement. SIGNIFICANCE: In the plasticity induction experiments, we should always be mindful of the fact that voluntary movement, including the target muscle, seriously influences the induced long-term effects of QPS.

Effects of L-Dopa and pramipexole on plasticity induced by QPS in human motor cortex.

Abnormal plasticity has been reported in the brain of patients with Parkinson's disease (PD), especially in the striatum. Although both L-Dopa and dopamine agonist remain to be the mainstay of the treatment in PD, their differential effects on cortical plasticity are unclear. We applied quadripulse stimulation (QPS) over the primary motor cortex (M1) in ten normal subjects to induce bidirectional long-term motor cortical plasticity. A long-term potentiation (LTP)-like effect was induced in the primary motor cortex (M1) by high-frequency QPS5 (interpulse interval of 5 ms) over M1, whereas a long-term depression (LTD)-like effect was induced by low-frequency QPS50 (interpulse interval of 50 ms), and the effects lasted up to 90 min after the stimulation pulses have ceased. In a double-blind randomized placebo-controlled crossover design, L-Dopa carbidopa 100 mg, pramipexole 1.5 mg [150 mg LED (L-Dopa equivalent dose)], or placebo was administered to the subjects 30 min before applying QPS. L-Dopa enhanced both LTP- and LTD-like plasticity as compared to placebo. In contrast, neither an LTP-like effect nor an LTD-like effect was modulated by pramipexole. The lack of LTP enhancement by pramipexole is compatible with the finding that D1 activation strengthens LTP because pramipexole is almost purely a D2 agonist. The lack of LTD enhancement by pramipexole is also consistent with the finding that both D1 and D2 coactivation is required for LTD. This is the first report to show that dopamine enhances LTD as well as LTP in the human brain and that coactivation of D1 and D2 is a requisite for LTD enhancement in normal humans.

Volitional walking via upper limb muscle-controlled stimulation of the lumbar locomotor center in man.

Gait disturbance in individuals with spinal cord lesion is attributed to the interruption of descending pathways to the spinal locomotor center, whereas neural circuits below and above the lesion maintain their functional capability. An artificial neural connection (ANC), which bridges supraspinal centers and locomotor networks in the lumbar spinal cord beyond the lesion site, may restore the functional impairment. To achieve an ANC that sends descending voluntary commands to the lumbar locomotor center and bypasses the thoracic spinal cord, upper limb muscle activity was converted to magnetic stimuli delivered noninvasively over the lumbar vertebra. Healthy participants were able to initiate and terminate walking-like behavior and to control the step cycle through an ANC controlled by volitional upper limb muscle activity. The walking-like behavior stopped just after the ANC was disconnected from the participants even when the participant continued to swing arms. Furthermore, additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in voluntary walking. These results demonstrate that the ANC induces volitionally controlled, walking-like behavior of the legs. This paradigm may be able to compensate for the dysfunction of descending pathways by sending commands to the preserved locomotor center at the lumbar spinal cord and may enable individuals with paraplegia to regain volitionally controlled walking.

[Two cases of posterior spinal artery syndrome (PSAS)].

We have reported two patients with posterior spinal artery syndrome. Both of them had sudden onset back pain, paraparesis, loss of deep sensation and bladder-bowel disturbances. MRI disclosed spinal cord lesions positioned at its posterior part including the posterior column or posterior horn at thoracic levels. Spinal artery syndrome is a rare disorder, especially the posterior spinal artery syndrome (PSAS). In our department, only ten patients had spinal artery syndrome out of 2,064 patients admitted to our hospital these 20 years. All the other 8 patients had anterior spinal artery syndrome. It supports the notion that PSAS is rare. The detection rate of PSAS may increase after the routine use of spinal MRI in clinical practice. Our two patients had bilateral, symmetric symptoms. These symmetric signs and symptoms are usually seen in PSAS. The bilateral posterior spinal arteries connect with each other through many complex anastomoses. Moderate blood flow insufficiency may produce no clinical symptoms because of compensation by these anastomoses. When symptoms appear, these anastomoses do not compensate blood flow deficit and may produce bilateral symptoms.

[Infliximab treatment trial in a patient with neuro-Behçet's disease unresponsive to other treatments].

A 22-year-old man with a previous uveitis episode was admitted to our hospital because of persistent hiccup. On admission, he presented right-upper quadrantanopia, mydriasis and lack of the light reflex in the left eye, left-sided hemiplegia, and bilateral pathologic hyperreflexia. The MR fluid attenuated inversion recovery images showed left side dominant, high intensity lesions on the brainstem and the diencephalon. The HLA-B51 was positive. The CSF IL-6 was extremely elevated (998 pg/ml: reference value < = 6.0 pg/ml). Based on these, we concluded he had the neuro-Behçet's disease and treated him by high dose intravenous corticosteroids. This treatment improved his symptoms and MRI lesions, and decreased the CSF IL-6 levels initially. On 13th day after the first his discharge, however, dysarthria appeared and the CSF IL-6 levels elevated again. In addition to the high dose intravenous corticosteroids therapy for acute attack, 15 mg/week of methotrexate was started to prevent the recurrence. Even with this prevention, meningitis related to neuro-Behçet's disease occurred within six weeks. We administered 5 mg/kg of infliximab intravenously at 0, 2, 6, and 14 weeks. After the infliximab treatment, his symptoms improved and the IL-6 levels decreased, and no recurrence has occurred. This case supports that infliximab, anti-TNF-alpha agent, is a good candidate for neuro-Behçet's disease treatment when it is resistant to conventional immunosuppressive agents such as corticosteroids or methotrexate.