Quadripulse transcranial magnetic stimulation inducing long-term depression in healthy subjects may increase seizure risk in some patients with intractable epilepsy.

Objective: This study aimed to assess the efficacy and safety of quadripulse transcranial magnetic stimulation-50 (QPS-50) in patients with intractable epilepsy. Methods: Four patients were included in the study. QPS-50, which induces long-term depression in healthy subjects, was administered for 30 min on a weekly basis for 12 weeks. Patients' clinical symptoms and physiological parameters were evaluated before, during, and after the repeated QPS-50 period. We performed two control experiments: the effect in MEP (Motor evoked potential) size after a single QPS-50 session with a round coil in nine healthy volunteers, and a follow-up study of physiological parameters by repeated QPS-50 sessions in four other healthy participants. Results: Motor threshold (MT) decreased during the repeated QPS-50 sessions in all patients. Epileptic symptoms worsened in two patients, whereas no clinical worsening was observed in the other two patients. In contrast, MT remained unaffected for 12 weeks in all healthy volunteers. Conclusions: QPS-50 may not be effective as a treatment for intractable epilepsy. Significance: In intractable epilepsy patients, administering repeated QPS-50 may paradoxically render the motor cortex more excitable, probably because of abnormal inhibitory control within the epileptic cortex. The possibility of clinical aggravation should be seriously considered when treating intractable epilepsy patients with non-invasive stimulation methods.

Hemophagocytic Lymphohistiocytosis Associated with Disseminated Nontuberculous Mycobacterial Infection in a Patient with Mesenteric Panniculitis.

Mesenteric panniculitis is a chronic inflammatory disease characterized by non-specific inflammation of the adipose tissue in the mesentery. Hemophagocytic lymphohistiocytosis is a life-threating disease associated with aberrant macrophage overactivation, in which infections can be a leading cause in immunocompromised hosts. Here, we report a rare case of mesenteric panniculitis and hemophagocytic lymphohistiocytosis complicated by disseminated Mycobacterium intracellulare. A 71-year-old male with mesenteric panniculitis was admitted to our hospital for fever and pancytopenia. He was treated with oral prednisolone (15 mg/day) and cyclosporin A (150 mg/day) at presentation. Physical and laboratory examinations revealed disseminated infection with nontuberculous mycobacteria; Mycobacterium intracellulare was detected in cultures of cerebrospinal fluid, blood, sputum, and gastric fluid. Patient signs and symptoms fulfilled the five criteria for a diagnosis of hemophagocytic lymphohistiocytosis, including fever, cytopenia, hemophagocytosis, hyperferritinemia, and high soluble interleukin-2 receptor levels. Therefore, the diagnosis of nontuberculous mycobacteria-associated hemophagocytic lymphohistiocytosis was established. An anti-mycobacterial chemotherapy including chloramphenicol (800 mg/day), rifampin (450 mg/day) and ethambutol (750 mg/day) together with streptomycin (750 mg twice per week) was initiated at 30 days after admission; maintenance doses of prednisolone were increased to 60 mg/day. Fever and pancytopenia improved in response to anti-mycobacterial chemotherapy. The present case suggests that mesenteric panniculitis could be complicated with hemophagocytic lymphohistiocytosis caused by immunosuppressive therapy-associated infections as well as underlying disease activity. In conclusion, the possibility of disseminated nontuberculous mycobacteria infection with hemophagocytic lymphohistiocytosis should be considered if unexplained fever or hematological dyscrasia were presented in patients of mesenteric panniculitis.

IgG4-Related Disease Complicated by Brain Parenchymal Lesions Successfully Treated with Corticosteroid Therapy: A Case Report.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is distinguished by the infiltration of IgG4-positive plasma cells in a variety of tissues and organs including the pancreas, salivary glands, retroperitoneal lesions, kidney, and lymph nodes with elevated serum IgG4 levels. Even so, central nervous system (CNS) lesions such as brain parenchymal lesions associated with IgG4-RD are scarce. So far, only six cases of IgG4-RD in relation with brain parenchymal lesions have been described, with its characteristics still being not clear. Here we have detailed a case of IgG4-RD with brain parenchymal lesions and reviewed previously-reported cases of IgG4-RD with brain parenchymal lesions. A 62-year-old Japanese male suffering from lung silicosis was admitted to our hospital for abdominal discomfort and altered consciousness. He has shown no major neurologic abnormalities except for drowsiness, urinary retention, and fecal incontinence. Brain magnetic resonance imaging has shown scattered hyperintense signals in the brain parenchyma. The serum IgG4 levels were elevated and systemic lymph nodes were enlarged. Biopsy from inguinal lymph nodes has shown massive infiltration of IgG4-positive plasma cells: the ratio of IgG4-positive/IgG-positive plasma cells was nearly 100%. Based on clinical courses, images, laboratory data, and pathological findings, a diagnosis of IgG4-RD that was complicated by brain parenchymal lesions and sacral nerve disturbance was confirmed. The patient was then given methylprednisolone pulse therapy (1g for 3 days) succeeding oral prednisolone (1 mg per body weight). The clinical and radiological improvements together with steroid therapy proposed IgG4-RD to be the cause of the lesions.

Effects of electromagnetic fields from long-term evolution on awake electroencephalogram in healthy humans.

Mobile phones are indispensable for daily life, and the adverse effects of the electromagnetic field (EMF) emitted by mobile phones have been a great concern. We studied the effects of long-term evolution (LTE) -like EMF for 30 min on an awake electroencephalogram (EEG). Thirty-eight healthy volunteers, aged 20-36 years old, participated in this study. The maximum local SAR (specific absorption rate) averaged over 10-g mass was 2.0 W/kg. The EEG was recorded before and after real or sham exposures. The effects of exposure conditions (real or sham) and the recording time (before, during, and after exposure) on each EEG power spectrum of θ, α, and ß frequency ranges were analyzed. The θ and α band waves were enhanced after both exposure conditions. These results may be explained by the participants' drowsiness during the EEG recording in both exposures. We conclude that an LTE-like exposure for 30 min in this study showed no detectable harmful effects on awake EEGs in healthy humans.

A Unique Shape of Brainstem Lesion that Caused Orthostatic Hypotension in Anti-NMDAR Encephalitis.

After experiencing upper respiratory-tract symptoms, a 41-year-old woman developed encephalitis with consciousness disturbance and respiratory failure. She had external ophthalmoplegia and facial diplegia. Magnetic resonance imaging revealed a brainstem lesion with spared longitudinal pontine bundles. Abnormal findings of the brainstem auditory-evoked potentials and blink reflex supported brainstem damage. The patient was positive for anti-N-methyl-D-aspartate receptor (NMDAR) antibodies. Repeated immunological treatments improved her symptoms, but severe orthostatic hypotension emerged. A head-up tilt test revealed no arginine vasopressin response to hypotension. The atypical symptoms of this case highlighted that the brainstem is one of the pivotal regions in anti-NMDAR encephalitis.

Frequency-dependent current perception threshold in healthy Japanese adults.

The purpose of the study involves measuring the threshold for electric currents (i.e., current perception threshold or CPT) under several stimulating current frequencies. Specifically, current perception threshold (CPT) was measured in 53 healthy volunteers between the ages of 21 and 67. The stimulation currents were applied on the right index finger with stimulus frequencies in the range of 50 Hz - 300 kHz. The method of limits and method of constant stimuli were combined to measure the CPT. In a manner consistent with the findings obtained by previous studies, the results indicated that CPT was higher in men than in women and in older individuals than in young subjects. Bioelectromagnetics. 9999:XX-XX, 2019. © 2019 Bioelectromagnetics Society.

Inflammatory myopathy with myasthenia gravis: Thymoma association and polymyositis pathology.

Objective: To provide evidence that idiopathic inflammatory myopathy (IM) with myasthenia gravis (MG) frequently shows thymoma association and polymyositis (PM) pathology and shares clinicopathologic characteristics with IM induced by immune checkpoint inhibitors (ICIs). Methods: We analyzed the clinicopathologic features of 10 patients with idiopathic IM and MG identified in 970 consecutive patients with biopsy-proven IM. Results: Seven patients (70%) had thymoma. IM and MG were diagnosed with more than 5-year time difference in 6 thymomatous patients and within 1 year in 1 thymomatous and 3 nonthymomatous patients. Seven thymomatous patients showed rhabdomyolysis-like features with respiratory failure (4/7), dropped head (3/7), cardiac involvement (2/7), and positive anti-acetylcholine receptor (anti-AChR) and anti-titin antibodies (7/7 and 4/6, respectively) but rarely showed ocular symptoms (2/7) or decremental repetitive nerve stimulation (RNS) responses (1/7) at IM diagnosis. Three nonthymomatous patients showed acute cardiorespiratory failure with rhabdomyolysis-like features (1/3), positive anti-AChR and anti-titin antibodies (3/2 and 2/2, respectively), and fluctuating weakness of the skeletal muscle without ocular symptoms (3/3). Muscle pathology showed a PM pathology with infiltration of CD8-positive CD45RA-negative T-lymphocytes (9/9), scattered endomysial programmed cell death 1 (PD-1)-positive cells (9/9), and overexpression of programmed cell death ligand 1 (PD-L1) on the sarcolemma of muscle fibers around the infiltrating PD-1-positive cells (7/9). Conclusion: Rhabdomyolysis-like features, positive anti-AChR antibody without decremental RNS responses, and PD-L1 overexpression are possible characteristics shared by ICI-induced IM. Frequent thymoma association in patients with idiopathic IM and MG may suggest thymoma-related immunopathogenic mechanisms, including dysregulation of the immune checkpoint pathway.

A significant correlation between cauda equina conduction time and cerebrospinal fluid protein in chronic inflammatory demyelinating polyradiculoneuropathy.

We investigated the relationship between the involvement of the cauda equina in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the increment of cerebrospinal fluid (CSF) protein. We measured cauda equina conduction time (CECT) in 14 CIDP patients using magnetic stimulation with a MATS coil. Statistical analysis revealed that CECT and CSF protein had a significant positive linear correlation. Conduction time of the peripheral nerve trunk, in contrast, had no significant linear correlation with CSF protein. We revealed that the involvement of the cauda equina and increment of CSF protein are closely related. In CIDP cases with elevated CSF protein, spinal nerves including the cauda equina are very likely involved.

Influence of radiofrequency-electromagnetic waves from 3rd-generation cellular phones on fertilization and embryo development in mice.

The purpose of this study was to evaluate the effects of 3rd-generation (3G) cellular phone radiofrequency-electromagnetic wave (RF-EMW) exposure on fertilization and embryogenesis in mice. Oocytes and spermatozoa were exposed to 3G cellular phone RF-EMWs, 1.95 GHz wideband code division multiple access, at a specific absorption rate of 2 mW/g for 60 min, or to sham exposure. After RF-EMW exposure, in vitro fertilization and intracytoplasmic sperm injection were performed. Rates of fertilization, embryogenesis (8-cell embryo, blastocyst), and chromosome aberration were compared between the combined spermatozoa and oocyte groups: both exposed, both non-exposed, one exposed, and the other non-exposed. Rates of fertilization, embryogenesis, and blastocyst formation did not change significantly across the four groups. Considering that the degree of exposure in the present study was ≥100 times greater than daily exposure of human spermatozoa and even greater than daily exposure of oocytes, the present results indicate safety of RF-EMW exposure in humans. Bioelectromagnetics. 38:466-473, 2017. © 2017 Wiley Periodicals, Inc.

Impairment of triad conditioned facilitation in amyotrophic lateral sclerosis.

OBJECTIVES: The triad conditioned facilitation (TCF) technique has been shown to detect motor cortical intrinsic rhythms depending on the functioning of specific cortical layers by measuring motor evoked potential (MEP) enhancement after a triad of conditioning TMS pulses at a certain interval. However, the influence of cortical degeneration on TCF is still undetermined. We therefore studied TCF in patients with amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterised by degeneration of the motor cortex. METHODS: Thirteen patients with ALS and 11 age-matched disease control patients with cervical myelopathy (CM) or radiculopathy (CR) participated in the study. We studied short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and TCF using the paired-pulse and triad conditioned TMS paradigm. RESULTS: TCF was significantly reduced in ALS patients compared to CM/CR patients, who had normal TCF. SICI and ICF did not differ between groups. CONCLUSION: The absence of TCF with preserved SICI and ICF suggests changes in the intrinsic rhythm generation within the motor cortex due to cortical neurodegeneration in ALS patients. In contrast, TCF was normal in patents with CM/CR in whom the motor cortical intrinsic circuits are not involved. This technique may be valuable to differentiate patients with ALS from those with CM/CR.

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.

Somatosensory-evoked potential modulation by quadripulse transcranial magnetic stimulation in patients with benign myoclonus epilepsy.

OBJECTIVE: In patients with benign myoclonus epilepsy (ME), giant sensory-evoked potential (SEP) reflects the hyperexcitability of the sensory cortex. The aim of this study was to compare the effect of quadripulse transcranial magnetic stimulation (QPS) on the median nerve SEP between ME patients and healthy subjects. METHODS: Ten healthy volunteers and six ME patients with giant SEP participated in this study. QPSs at interpulse intervals (IPIs) of 5, 30, 50, 100, 500 and 1250 ms were applied over the left primary motor cortex (M1) for 30 min. The peak-to-peak amplitudes of N20 to P25 (N20-P25) and P25 to N33 (P25-N33) components were measured at the left somatosensory cortex. RESULTS: In healthy participants, the P25-N33 was bidirectionally modulated by QPS over M1, following the Bienenstock-Cooper-Munro (BCM) theory. The N20-P25 was not affected by any QPSs. In ME patients, the giant P25-N33 was potentiated after any QPSs. Furthermore, the N20-P25 was also potentiated after QPS at IPIs of 5, 30, 50 100 or 500 ms. CONCLUSIONS: In ME patients, the cascade for long-term depression-like effects may be impaired. SIGNIFICANCE: The giant SEP was furthermore enhanced by 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.

Complex fasciculation potentials and survival in amyotrophic lateral sclerosis.

OBJECTIVE: We investigated the relationship between fasciculation potentials (FPs) and survival in patients with ALS. METHODS: In 85 ALS patients, we prospectively performed needle EMG in five to seven muscles of each patient. The shape of the detected FPs was analyzed by inspection, and FPs with >4 phases were judged as complex FPs. We analyzed the correlation between complex FPs and survival period using the Cox proportional hazard model. RESULTS: Complex FPs were observed in 47 patients, more frequently in the muscles with normal strength or mild weakness. The presence of complex FPs was associated with shorter survival (hazard ratio 3.055; p=0.004). The greater the number of muscles with complex FPs, the shorter the survival and the faster the progression speed. CONCLUSION: Wide distribution of complex FPs is associated with shorter survival in ALS. SIGNIFICANCE: Complex FPs are useful to predict prognosis of ALS patients and should be evaluated in the EMG examination.

Effects of electromagnetic fields emitted from W-CDMA-like mobile phones on sleep in humans.

In this study, we investigated subjective and objective effects of mobile phones using a Wideband Code Division Multiple Access (W-CDMA)-like system on human sleep. Subjects were 19 volunteers. Real or sham electromagnetic field (EMF) exposures for 3 h were performed before their usual sleep time on 3 consecutive days. They were exposed to real EMF on the second or third experimental day in a double-blind design. Sleepiness and sleep insufficiency were evaluated the next morning. Polysomnograms were recorded for analyses of the sleep variables and power spectra of electroencephalograms (EEG). No significant differences were observed between the two conditions in subjective feelings. Sleep parameters including sleep stage percentages and EEG power spectra did not differ significantly between real and sham exposures. We conclude that continuous wave EMF exposure for 3 h from a W-CDMA-like system has no detectable effects on human sleep.

Cortical hemoglobin concentration changes underneath the coil after single-pulse transcranial magnetic stimulation: a near-infrared spectroscopy study.

Using near-infrared spectroscopy (NIRS) and multichannel probes, we studied hemoglobin (Hb) concentration changes when single-pulse transcranial magnetic stimulation (TMS) was applied over the left hemisphere primary motor cortex (M1). Seventeen measurement probes were centered over left M1. Subjects were studied in both active and relaxed conditions, with TMS intensity set at 100%, 120%, and 140% of the active motor threshold. The magnetic coils were placed so as to induce anteromedially directed currents in the brain. Hb concentration changes were more prominent at channels over M1 and posterior to it. Importantly, Hb concentration changes at M1 after TMS differed depending on whether the target muscle was in an active or relaxed condition. In the relaxed condition, Hb concentration increased up to 3-6 s after TMS, peaking at ∼6 s, and returned to the baseline. In the active condition, a smaller increase in Hb concentrations continued up to 3-6 s after TMS (early activation), followed by a decrease in Hb concentration from 9 to 12 s after TMS (delayed deactivation). Hb concentration changes in the active condition at higher stimulus intensities were more pronounced at locations posterior to M1 than at M1. We conclude that early activation occurs when M1 is activated transsynaptically. The relatively late deactivation may result from the prolonged inhibition of the cerebral cortex after activation. The posterior-dominant activation at higher intensities in the active condition may result from an additional activation of the sensory cortex due to afferent inputs from muscle contraction evoked by the TMS.

Quadri-pulse stimulation induces stimulation frequency dependent cortical hemoglobin concentration changes within the ipsilateral motor cortical network.

BACKGROUND: Imaging studies investigating repetitive transcranial magnetic stimulation (rTMS) mediated hemodynamic consequences revealed inconsistent results, mainly due to differences in rTMS parameters and technical difficulties with simultaneous recordings during rTMS. OBJECTIVE/HYPOTHESIS: Quadri-pulse rTMS (QPS) induces bidirectional long-term plasticity of the human primary motor cortex (M1). To evaluate its on-line effects, near infrared spectroscopy (NIRS) recordings were performed during QPS. We hypothesized that on-line effects during QPS are different from long-term aftereffects. METHODS: Using a novel TMS - on-line multi-channel NIRS setup we recorded hemoglobin concentration [Hb] changes at the stimulated M1 and adjacent sensory-motor areas during QPS protocols inducing oppositely directed aftereffects (QPS-5: interstimulus interval (ISI) 5 ms, potentiation; QPS-50: ISI 50 ms, depression). In two experiments we studied NIRS changes during either single or repeated QPS bursts. RESULTS: The repetitive QPS-5 bursts significantly decreased oxyhemoglobin concentration ([oxy-Hb]) in the ipsilateral M1. A single QPS-5 burst decreased [oxy-Hb] in the M1 and premotor cortex. QPS-50 induced no significant NIRS changes at any sites. CONCLUSIONS: QPS can significantly alter cortical hemodynamics depending on the stimulation frequency. While bidirectional long-term aftereffects of QPS reflect synaptic efficacy changes, unidirectional on-line effects during QPS may represent pure electrophysiological property changes within the cell membrane or synapse. Since neuronal postexcitatory inhibitory postsynaptic potentials typically peak within the first 10-20 ms, only pulses delivered at higher frequencies may lead to summation of the inhibitory effects, resulting in [oxy-Hb] decrease only after QPS-5. Our new TMS-NIRS setup may be valuable to investigate TMS induced neurovascular coupling mechanisms in humans.

Bidirectional modulation of sensory cortical excitability by quadripulse transcranial magnetic stimulation (QPS) in humans.

OBJECTIVE: Quadripulse transcranial magnetic stimulation (QPS) is a newly designed patterned repetitive transcranial magnetic stimulation (TMS). Previous studies of QPS showed bidirectional effects on the primary motor cortex (M1), which depended on its inter-stimulus interval (ISI): motor evoked potentials (MEPs) were potentiated at short ISIs and depressed at long ISIs (homotopic effects). These physiological characters were compatible with synaptic plasticity. In this research, we studied effects of QPS on the primary sensory cortex (S1). METHODS: One burst consisted of four monophasic TMS pulses at an intensity of 90% active motor threshold. The ISI of four pulses was set at 5 ms (QPS-5) or at 50 ms (QPS-50). Same bursts were given every 5s for 30 min. QPS-5 and QPS-50 were performed over three areas (M1, S1 and dorsal premotor cortex (dPMC)). One sham stimulation session was also performed. Excitability changes of S1 were evaluated by timeline of somatosensory evoked potentials (SEPs). RESULTS: QPS-5 over M1 or dPMC enhanced the P25-N33 component of SEP, and QPS-50 over M1 depressed it. By contrast, QPSs over S1 had no effects on SEPs. CONCLUSIONS: QPSs over motor cortices modulated the S1 cortical excitability (heterotopic effects). Mutual connections between dPMC or M1 and S1 might be responsible for these modulations. SIGNIFICANCE: QPSs induced heterotopic LTP or LTD-like cortical excitability changes.

Ataxic hemiparesis: neurophysiological analysis by cerebellar transcranial magnetic stimulation.

The aim of this study was to investigate physiological mechanisms underlying ataxia in patients with ataxic hemiparesis. Subjects were three patients with ataxic hemiparesis, whose responsible lesion was located at the posterior limb of internal capsule (case 1), thalamus (case 2), or pre- and post-central gyri (case 3). Paired-pulse transcranial magnetic stimulation (TMS) technique was used to evaluate connectivity between the cerebellum and contralateral motor cortex. The conditioning cerebellar stimulus was given over the cerebellum and the test stimulus over the primary motor cortex. We studied how the conditioning stimulus modulated motor evoked potentials (MEPs) to the cortical test stimulus. In non-ataxic limbs, the cerebellar stimulus normally suppressed cortical MEPs. In ataxic limbs, the cerebellar inhibition was not elicited in patients with a lesion at the posterior limb of internal capsule (case 1) or thalamus (case 2). In contrast, normal cerebellar inhibition was elicited in the ataxic limb in a patient with a lesion at sensori-motor cortex (case 3). Lesions at the internal capsule and thalamus involved the cerebello-thalamo-cortical pathways and reduced the cerebellar suppression effect. On the other hand, a lesion at the pre- and post-central gyri should affect cortico-pontine pathway but not involve the cerebello-thalamo-cortical pathways. This lack of cerebello-talamo-cortical pathway involvement may explain normal suppression in this patient. The cerebellar TMS method can differentiate cerebellar efferent ataxic hemiparesis from cerebellar afferent ataxic hemiparesis.