Shinji Ohara

Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy

SummaryWe studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 μm in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.

Primary somatosensory cortex is actively involved in pain processing in human

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.

Low-frequency electric cortical stimulation has an inhibitory effect on epileptic focus in mesial temporal lobe epilepsy

Summary:  Purpose: This study was conducted to investigate the effect of low‐frequency electric cortical stimulation on epileptic focus in humans.

Lesions Limited to the Human Thalamic Principal Somatosensory Nucleus (Ventral Caudal) Are Associated with Loss of Cold Sensations and Central Pain

Central pain is neuropathic pain resulting from a lesion of the CNS, such as a stroke [poststroke central pain (CPSP)]. Lesions involving the posterior thalamus lead to reduction or loss of sensation and to CPSP, although the responsible nuclei have not been identified. We now examine the hypotheses that thalamic lesions must extend posterior to the ventral caudal nucleus (Vc) and include ventral medial posterior nucleus (VMpo), to result in loss of cold sensibility and CPSP. Patients with small thalamic strokes associated with CPSP were evaluated by atlas-based mapping of magnetic resonance imaging scans, and by somatosensory testing. All lesions involved posterior Vc; two lesions also involved nuclei posterior to Vc, but not VMpo. All patients tested had alterations of cold pain sensation and tactile sensation, as measured by von Frey hairs. Three patients had altered cool sensation, and the patient with the least involvement of Vc had normal cool thresholds, suggesting that a critical volume of Vc must be involved before cool sensation is impaired. Perception of warm was impaired only in lesions involving nuclei posterior to Vc. Heat pain perception was never affected. In a subject with cold allodynia, a single-subject protocol PET study measured the responses to immersion of either hand in a 20°C waterbath. The scan during stimulation of the affected hand was characterized by intense activation of contralateral sensorimotor cortex. Therefore, there are modality-specific subnuclear structures in the posterior thalamus, but lesions of Vc not involving VMpo are sufficient to impair cold sensibility and to produce CPSP.

Anti-neuronal autoantibody in Hashimoto's encephalopathy: neuropathological, immunohistochemical, and biochemical analysis of two patients

Hashimotos encephalopathy (HE) is thought to be caused by disorders of immune mechanisms. Although immunologically mediated central nervous system vasculitis or unidentified anti-neuronal autoantibodies have been suspected of causing HE, its pathogenesis is still unclear. For the study presented here, two patients with typical clinical and laboratory/electrophysiological findings of HE were analyzed to clarify the role of anti-neuronal autoantibodies in the pathogenesis of HE. The autopsied brain of one of the patients was histopathologically examined. For Western blotting analysis and immunohistochemistry, serum and purified immunoglobulin G obtained from the other patient were used. Autopsy revealed no evidence of central nervous system vasculitis or other abnormal findings in the brain. The patients serum contained an anti-neuronal autoantibody that immunohistochemically labeled neurons of mouse and human cerebral cortices and reacted with the 36-kDa antigenic protein present in a soluble fraction obtained from human cerebral cortex. Our results indicate that anti-neuronal autoantibodies may be associated with the pathogenesis of HE.

Hemiballism with hyperglycemia and striatal T1-MRI hyperintensity: an autopsy report.

We report on an autopsy findings of a 92‐year‐old male with hemiballism‐hemichorea associated with hyperglycemia and striatal hyperintensity on T1‐weighed magnetic resonance imaging (MRI), a recently described clinicoradiological syndrome. Histologically, the putamen contralateral to the hemiballism consisted of multiple foci of recent infarcts associated with reactive astrocytic and interneuronal response. Substrate responsible for the MRI signal changes is still inconclusive.

Electrocorticogram–electromyogram coherence during isometric contraction of hand muscle in human

OBJECTIVE To clarify how the primary sensorimotor and supplementary motor areas are involved in the generation of the rhythmicity of electromyogram (EMG) activity during continuous muscle contraction. METHOD We analyzed the coherence between subdurally recorded cortical electroencephalograms (EEG) and EMGs of the contralateral wrist extensor muscle during continuous isometric contraction in 8 patients with medically intractable epilepsy. RESULTS In all subjects, a significant coherence between the primary motor area (M1) and EMG was observed at the peak frequency of 15+/-3 Hz (means+/-SD). In the primary somatosensory area (S1) of 7 subjects and the supplementary motor area proper (SMA proper) of 4 subjects, significant coherence with EMG was observed at 12+/-5 and 15+/-4 Hz, respectively. The time lags revealed by cross-correlogram were 10+/-3, 7+/-1 and 22+/-8 ms in the M1, S1 and SMA proper, respectively, with the EMG lagging in all areas. CONCLUSION These findings suggest that the rhythmic activity in the SMA proper, as well as in the S1 and M1, is related to the generation of the rhythmicity of EMG activity.

Multisensory convergence at human temporo-parietal junction – epicortical recording of evoked responses

OBJECTIVE Previous lesion studies in patients and functional imaging studies in normal subjects have led to the notion that the temporo-parietal junction (TPJ) has an integrative function for multisensory inputs. However, its electrophysiological properties such as response latencies and distributions of responses to various stimulus modalities in humans have not been fully investigated. The aim of the study is to clarify this issue. METHODS We recorded evoked potentials to different kinds of sensory stimuli including somatosensory, auditory and visual modalities in 6 patients with intractable partial epilepsy, who underwent chronic implantation of subdural electrodes in TPJ for presurgical evaluation. RESULTS In 5 out of 6 subjects, at least one electrode located in TPJ for each subject showed a maximum somatosensory evoked response commonly to electric, passive joint motion and pain stimuli. These electrodes showed the maximum responses also to tone stimuli in all of 4 subjects studied, and to visual motion stimuli in 3 out of 5 subjects studied. The polarity was consistent regardless of the stimulus modality within each individual subject, although the anatomical location, polarity and latency varied among subjects. CONCLUSIONS A small area in TPJ for each individual subject receives sensory information of multiple modalities possibly coming from different receptive sites, although the electrophysiological properties of the responses may vary among subjects. SIGNIFICANCE We confirmed the convergence of somatosensory, auditory and visual evoked responses at human TPJ.

Functional mapping of human medial frontal motor areas

Abstract. Two functional brain-mapping techniques, functional magnetic resonance imaging (fMRI) and cortical stimulation by chronically implanted subdural electrodes, were used in combination for presurgical evaluation of three patients with intractable, partial motor seizures. Brain mapping was focused on characterizing motor-related areas in the medial frontal cortex, where all patients had organic lesions. Behavioral tasks for fMRI involved simple finger and foot movements in all patients and mental calculations in one of them. These tasks allowed us to discriminate several medial frontal motor areas: the presupplementary motor areas (pre-SMA), the somatotopically organized SMA proper, and the foot representation of the primary motor cortex. All patients subsequently underwent cortical stimulation through subdural electrodes placed onto the medial hemispheric wall. In each patient, the cortical stimulation map was mostly consistent with that patients brain map by fMRI. By integrating different lines of information, the combined fMRI and cortical stimulation map will contribute not only to safe and effective surgery but also to further understanding of human functional neuroanatomy.

Human supplementary motor area is active in preparation for both voluntary muscle relaxation and contraction : Subdural recording of bereitschaftspotential

Bereitschaftspotentials (BPs) preceding muscle relaxation and contraction were compared by using subdural electrodes which were implanted onto the right medial frontal surface in two patients with supplementary motor area (SMA) seizure. The applied movement paradigm (muscle relaxation and contraction tasks) was completely the same as employed in our previous study [Terada, K., Ikeda, A., Nagamine, T. and Shibasaki, H., Electroenceph. clin. Neurophysiol., 95 (1995) 335-345]. In both patients, either negative or positive BPs were observed in the SMA-proper and supplementary negative motor area (SNMA) starting at 1.2-1.8 prior to both movements. In one patient, BP was more widespread in the relaxation task whereas more restricted to the hand area in the contraction task. In the other patient, the BPs were observed in the cortical area rostral to SNMA (pre-SMA), in addition to the SMA-proper, in both tasks. It is concluded that SMA-proper and SNMA, and probably pre-SMA as well, in humans are similarly active in preparation for both voluntary muscle contraction and relaxation.