Soichiro Mochio

Effects of 1-Hz repetitive transcranial magnetic stimulation on acute pain induced by capsaicin.

&NA; The aim of this study is to investigate the efficacy of 1‐Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) on acute pain induced by intradermal capsaicin injection and to elucidate its mechanisms by single‐photon emission computed tomography (SPECT). We compared time courses of a subjective scale of pain induced by intradermal capsaicin injection in seven normal subjects under three different conditions: rTMS over M1, sham stimulation, and control condition (natural course of acute pain without any stimulation). In ten normal subjects, using SPECT, we also studied differences in regional cerebral blood flow (rCBF) after capsaicin injection between two conditions: rTMS over M1 and the control condition. rTMS over M1 induced earlier recovery from acute pain compared with the sham or control conditions. Under rTMS over the right M1 condition compared with the control condition, the SPECT study demonstrated a significant relative rCBF decrease in the right medial prefrontal cortex (MPFC) corresponding to Brodmann area (BA) 9, and a significant increase in the caudal part of the right anterior cingulate cortex (ACC) corresponding to BA24 and the left premotor area (BA6). A region‐of‐interest analysis showed significant correlation between pain reduction and rCBF changes in both BA9 and BA24. We conclude that rTMS over M1 should have beneficial effects on acute pain, and its effects must be caused by functional changes of MPFC and caudal ACC.

Cardiovascular dysautonomia in de novo Parkinson's disease

BACKGROUND Clinical symptoms of Parkinsons disease (PD) include not only motor distress, but also autonomic dysfunction. OBJECTIVE To clarify the progression of autonomic nervous dysfunction in PD. METHODS The subjects were 44 patients with de novo PD. Autonomic nervous function, including cardiac sympathetic gain, was evaluated on the basis of cardiac radioiodinated metaiodobenzylguanidine (MIBG) uptake, the response to the Valsalva maneuver, and spectral analyses of the RR interval and blood pressure. RESULTS Decreased cardiac MIBG uptake was found even in patients with early stage PD. MIBG uptake gradually decreased with increased disease severity. Hemodynamic studies using the Valsalva maneuver revealed that patients with early stage PD had reduced baroreceptor reflex sensitivity (BRS) in phase II, but not phase IV. Blood pressures normally rose in phases II and IV, but the increments decreased with disease progression. In early stage PD, the low frequency power of the RR interval (RR-LF) and the ratio (LF/HF) of RR-LF to the high frequency component of the RR interval (RR-HF) were significantly lower than the respective control values, despite no significant difference in RR-HF; these variables decreased with disease progression. CONCLUSION Our results show that latent sympathetic nervous dysfunction without parasympathetic dysfunction, especially that involving the sinus node, is already present in early stage de novo PD. It is unclear whether the responsible lesion is central or peripheral.

Cardiovascular autonomic dysfunction in dementia with Lewy bodies and Parkinson's disease

OBJECTIVE We estimated the extent and pattern of cardiovascular autonomic dysfunction in dementia with Lewy bodies (DLB) as compared with that in Parkinsons disease (PD). METHODS We performed meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy of the heart and hemodynamic autonomic function testing using the Valsalva maneuver in 27 patients with DLB, 46 with PD, and 20 controls. RESULTS (123)I-MIBG uptakes in DLB were reduced as compared with those in control and PD. Hemodynamic studies revealed that DLB had decreased baroreceptor reflex and reduced responses of SBP in phases II and IV as compared with PD and control. SBP responses on standing and the difference in plasma norepinephrine (NE) concentrations between supine and standing positions were reduced in PD as compared with those in control. Furthermore, SBP responses on standing, plasma NE concentrations in supine and standing positions, and the difference in plasma NE concentrations between these positions were significantly lower in DLB than in PD and control. Plasma NE concentrations in DLB with orthostatic hypotension (OH) were lower than that in DLB without OH, although some patients who had DLB with orthostatic hypotension had relatively normal plasma NE levels. CONCLUSION Cardiovascular autonomic dysfunction is more severe in DLB than in PD and is usually caused by the loss of postganglionic sympathetic nervous function, although dysautonomia in some patients with DLB may result from preganglionic dysfunction.

Increased plasma TGF‐β1 in patients with amyotrophic lateral sclerosis

Objectives– To investigate the levels of transforming growth factor‐β1 (TGF‐β1) in plasma of patients with amyotrophic lateral sclerosis (ALS). Material and methods– The TGF‐β1 plasma concentrations were measured with an enzyme‐linked immunosorbent assay from 11 patients with ALS and 13 age matched healthy controls. Results– The mean TGF‐β1 plasma concentration in the patients with ALS (2.15 ± 0.80 ng/ml, mean ± SD) was significantly higher than in the healthy controls (1.59 ± 0.32 ng/ml) (P=0.031). There was a significant positive correlation between the TGF‐β1 plasma concentration in the patients with ALS and the duration of illness (r=0.66, P=0.028). Conclusion– Our findings provide evidence that in ALS the plasma concentration of TGF‐β1 increases significantly with the duration of illness. These results suggest that TGF‐β1 is involved in the disease process of ALS.

Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury

The rewiring of neural networks is a fundamental step in recovering behavioral functions after brain injury. However, there is limited potential for axonal plasticity in the adult CNS. The myelin-associated proteins Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp) are known to inhibit axonal plasticity, and thus targeting the inhibitory pathways they participate in is a potential means of promoting plasticity and functional recovery. Each of Nogo, MAG, and OMgp interacts with both the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Here, we determined whether blocking PirB activity enhances axonal reorganization and functional recovery after cortical injury. We found that axons of the contralesional corticospinal tract sprouted into the denervated side of the cervical spinal cord after unilateral injury of the motor cortex. The extent to which this axonal reorganization occurred was far greater in mice lesioned during early postnatal days than in mice lesioned at an age when myelin had begun to form. This suggests that myelin-associated proteins might limit axonal remodeling in vivo. However, the number of sprouting fibers within either the corticospinal or corticorubral tract was not enhanced in PirB−/− mice. Blocking PirB signaling also failed to enhance functional recovery with three motor tests. Our results suggest that blocking the function of PirB is not sufficient to promote axonal reorganization or functional recovery after cortical injury.

Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension

Background:  Clinical symptoms of Parkinson’s disease (PD) include not only motor distress, but also autonomic dysfunction.

Reduced cardiac 123I-MIBG uptake reflects cardiac sympathetic dysfunction in Lewy body disease

Objective: To examine the relation between the results of cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphy and cardiovascular autonomic function in Lewy body disease (LBD). Methods: The subjects were 66 patients with LBD, 44 of whom had Parkinson disease (PD), 10 PD with dementia (PDD), and 12 dementia with Lewy bodies (DLB); 20 age-matched healthy subjects were studied as controls. Cardiovascular autonomic function was evaluated on the basis of cardiac 123I-MIBG uptake, cardiovascular autonomic response on the Valsalva maneuver (VM), and systolic blood pressure (SBP) response on head-up tilt table (HUT) testing. Results: Patients with LBD had reduced cardiac 123I-MIBG uptake, cardiovascular autonomic response on the VM, and SBP response on HUT testing as compared with controls. Cardiac 123I-MIBG uptake and cardiovascular autonomic function in PDD and DLB were severely impaired as compared with those in PD. Cardiac 123I-MIBG uptake in LDB was not significantly related to vasomotor sympathetic function, baroreceptor reflex gain, cardiac parasympathetic function, or the changes in SBP on HUT testing. Cardiac 123I-MIBG uptake was, however, significantly related to the blood pressure overshoot in phase IV of the VM. Conclusion: Cardiac 123I-meta-iodobenzylguanidine uptake clinically reflects cardiac sympathetic dysfunction in Lewy body disease. GLOSSARY: BRS = baroreceptor reflex sensitivity; DLB = dementia with Lewy bodies; H/M ratio = the ratio of the average pixel count in the heart to that in the mediastinum; HUT = head-up tilt table test; LBD = Lewy body disease; MIBG = 123I-meta-iodobenzylguanidine; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PDD = Parkinson disease with dementia; phase II E = systolic blood pressure decreases in early phase II; phase II L = systolic blood pressure increases in late phase II; PRT = pressure recovery time; VM = Valsalva maneuver; ROI = region of interest; SBP = systolic blood pressure; TH = tyrosine hydroxylase.

Evaluation of Baroreflex Sensitivity by the Sequence Method Using Blood Pressure Oscillations and R–R Interval Changes during Deep Respiration

Background: Baroreflex sensitivity assessments have been considered to be important to evaluate cardiac autonomic neuropathy. The phenylephrine method, Valsalva maneuver or sequence method at rest caused several problems. We evaluated the usefulness of the sequence method during deep respiration. Method: Baroreflex sensitivity was evaluated in 20 normal volunteers and 50 patients with Parkinson’s disease. R–R intervals and systolic blood pressures were obtained by electrocardiogram and tonometry using a continuous blood pressure monitoring system. The sequence method is an evaluation of baroreflex sensitivity using sequences of 3 or more consecutive beats for 4 min. Baroreflex sensitivity was also assessed by the Valsalva maneuver at 5 beats before the peak systolic blood pressure of phase IV. The slope of the linear interrelationship between systolic blood pressure and the following R–R interval, i.e. baroreflex sensitivity (ms/mm Hg), was calculated with a correlation coefficient greater than 0.8. Result: The mean value of baroreflex sensitivity obtained by the Valsalva maneuver was 7.91 in normal volunteers and 5.35 in patients with Parkinson’s disease; the one obtained by the sequence method at rest was 9.10 in normal volunteers and 8.42 in patients with Parkinson’s disease, and the one obtained by the sequence method during deep respiration was 10.23 in normal volunteers and 6.73 in patients with Parkinson’s disease. In some cases with Parkinson’s disease, baroreflex sensitivities could not be found, whereas in all patients with Parkinson’s disease, the sequence method during deep respiration could be used for evaluations. Significant correlations were found among the baroreflex sensitivities obtained by the Valsalva maneuver, and the sequence method at rest or during deep respiration in normal volunteers and patients with Parkinson’s disease. Conclusions: The baroreflex sensitivity obtained by the sequence method during deep respiration could be investigated noninvasively in all cases with PD, being thus a useful method for clinical evaluation of baroreflex sensitivity.

Prolongation of QTc Interval in Patients with Parkinson’s Disease

QTc intervals were measured in 30 patients with Parkinsons disease and 30 healthy control subjects. The mean value of QTc intervals in patients with Parkinsons disease significantly exceeded that of healthy controls (418 +/- 14 ms vs. 403 +/- 18 ms). Prolongation of the QTc interval was unrelated to the administration of levodopa. The mean QTc interval in patients whose Hoehn and Yahr score was III or more was significantly greater than that of patients whose score was II or less (424 +/- 12 ms vs. 410 +/- 12 ms). A significant correlation between the QTc interval and the Valsalva ratio, as well as the overshoot, was identified. The QTc interval is closely related to autonomic nervous system dysfunction, including abnormal baroreceptor reflex function, in patients with Parkinsons disease.

Changes in auditory P300 event‐related potentials and brainstem evoked potentials in diabetes mellitus

To investigate the influence of diabetes mellitus on higher cognitive functions electrophysiologically, we studied auditory P300 event‐related potentials (P300) in 40 NIDDM patients, taking into account wave I‐V latencies (I‐V) in auditory brainstem evoked potentials, clinical parameters and head MRI findings. Compared with 20 controls, diabetics had significantly longer P300 and I‐V latencies. P300 latencies in diabetics correlated with neither I‐V. HbA1, blood glucose levels, nor disease duration. Of the 13 diabetics investigated neuroradiologically, four had lacunar infarcts with prolonged electrophysiological values. The remaining nine had normal MRI scans, but their physiological parameters were still significantly longer than those of controls. These findings suggest that NIDDM can independently alter higher cognitive and the central auditory pathway functions. Our data also suggest that these alterations occur regardless of the recent metabolic derangement and disease duration. Cerebrovascular ischemia, if present, also appears to contribute in part to cognitive alterations.