Takenori Uozumi

Motor potentials evoked by magnetic stimulation of the motor cortex in normal subjects and patients with motor disorders

Motor evoked potentials (MEPs) elicited by magnetic coil stimulation of motor cortex were studied at rest and during maximum voluntary muscle contraction in 20 normal subjects and 42 patients with motor disorders. MEP parameters employed in this study included: onset latency, amplitude, MEP/M wave amplitude ratio and background EMG/MEP area ratio. Maximum voluntary contraction increased the amplitude of MEPs compared to the size of M waves elicited by peripheral nerve stimulation. A reduced MEP/M wave amplitude ratio had a higher correlation with pyramidal tract involvement than did a prolonged MEP onset latency. Analysis of MEP parameters may help in the differential diagnosis of cerebral infarction, ALS and cervical spondylotic radiculomyelopathy. The inhibitory period which follows MEPs during voluntary contraction was observed in all subjects; the mean duration in normal subjects was 126.6 +/- 29.5 msec. The mean duration of the inhibitory period in patients with cerebral infarction, ALS and cervical spondylotic radiculomyelopathy was 73.9 +/- 41.7 msec, 79.5 +/- 54.5 msec and 85.1 +/- 36.5 msec, respectively. These values were significantly shorter than in normal subjects.

Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats.

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.

Age-dependent changes in physiological threshold asymmetries for the motor evoked potential and silent period following transcranial magnetic stimulation

OBJECTIVE To study the effect of age on the physiological threshold asymmetries for the motor evoked potential (MEP) and silent period (SP) following transcranial magnetic stimulation. METHODS We studied 63 right-handed subjects and 13 young left-handed subjects (19-39 years). The right-handers were classified into three age groups; 22 young (20-38 years), 20 middle-aged (40-58 years) and 21 old (61-82 years) subjects. We measured the MEP thresholds at rest and during voluntary contraction (VC), and the SP thresholds from the right and left abductor pollicis brevis (APB) muscles. We also measured the side to side differences of the F wave persistency and the F wave/M wave amplitude ratio from the same muscles. RESULTS Among young subjects, all of the MEP and SP thresholds for the right APB were significantly lower than those for the left APB in the right-handers, and the reverse was true in the left-handers. The results in the middle-aged right-handers were similar to those in the young right-handers, but in the old right-handers, none of the thresholds were different between the two sides. We did not find any asymmetries of the F wave in the subjects of any age group. CONCLUSION We speculate that the age-dependent threshold asymmetries are preferentially related to functional asymmetries at the cortical level.

Usefulness of Quantitative Susceptibility Mapping for the Diagnosis of Parkinson Disease

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping allows overcoming several nonlocal restrictions of susceptibility-weighted and phase imaging and enables quantification of magnetic susceptibility. We compared the diagnostic accuracy of quantitative susceptibility mapping and R2* (1/T2*) mapping to discriminate between patients with Parkinson disease and controls. MATERIALS AND METHODS: For 21 patients with Parkinson disease and 21 age- and sex-matched controls, 2 radiologists measured the quantitative susceptibility mapping values and R2* values in 6 brain structures (the thalamus, putamen, caudate nucleus, pallidum, substantia nigra, and red nucleus). RESULTS: The quantitative susceptibility mapping values and R2* values of the substantia nigra were significantly higher in patients with Parkinson disease (P < .01); measurements in other brain regions did not differ significantly between patients and controls. For the discrimination of patients with Parkinson disease from controls, receiver operating characteristic analysis suggested that the optimal cutoff values for the substantia nigra, based on the Youden Index, were >0.210 for quantitative susceptibility mapping and >28.8 for R2*. The sensitivity, specificity, and accuracy of quantitative susceptibility mapping were 90% (19 of 21), 86% (18 of 21), and 88% (37 of 42), respectively; for R2* mapping, they were 81% (17 of 21), 52% (11 of 21), and 67% (28 of 42). Pair-wise comparisons showed that the areas under the receiver operating characteristic curves were significantly larger for quantitative susceptibility mapping than for R2* mapping (0.91 versus 0.69, P < .05). CONCLUSIONS: Quantitative susceptibility mapping showed higher diagnostic performance than R2* mapping for the discrimination between patients with Parkinson disease and controls.

Sympathetic skin responses evoked by magnetic stimulation of the neck

We studied sympathetic skin responses (SSRs) following magnetic stimulation of the neck in 40 normal subjects and 54 patients with neurological diseases and active sweat gland densities (ASGDs) at the foot induced by pilocarpine in 39 patients. SSRs at the hand following magnetic stimulation showed the lowest coefficients of variability of the latencies and amplitudes in eight consecutive responses compared with SSRs following other types of stimuli (electrical and auditory stimulation, and deep inspiration) in 12 normal subjects. Fourteen of 38 patients with neuropathies (37%) showed the presence of SSRs after magnetic stimulation, but not after median nerve stimulation, although SSRs to magnetic stimulation corresponded with those to nerve stimulation in all patients with multiple sclerosis or multiple system atrophy. These results suggest that the absence of SSRs after nerve stimulation in patients with neuropathies may be due to abnormalities of the peripheral sensory afferent fibers. ASGDs significantly correlated with SSRs at the foot following magnetic stimulation, but not with those following nerve stimulation in patients with neuropathies. Magnetic stimulation of the neck is the highly reproducible method of evoking SSRs because this technique is able to produce strong sensory afferent inputs proximally. Furthermore, SSRs following magnetic stimulation, little influenced by sensory afferent fiber involvement, are very useful for evaluating the postganglionic sympathetic function in patients with neuropathies.

A novel tract imaging technique of the brainstem using phase difference enhanced imaging: normal anatomy and initial experience in multiple system atrophy

ObjectivesTo develop a new tract imaging technique for visualising small fibre tracts of the brainstem and for detecting the abnormalities in multiple system atrophy of the cerebellar type (MSA-C) using a phase difference enhanced (PADRE) imaging technique, in which the phase difference between the target and surrounding tissue is selectively enhanced.MethodsTwo neuroradiologists compared the high-spatial-resolution PADRE imaging, which was acquired from six healthy volunteers, three patients with MSA-C, and 7 patients with other types of neurodegenerative diseases involving the brainstem or cerebellum.ResultsVarious fine fibre tracts in the brainstem, the superior and inferior cerebellar peduncles, medial lemniscus, spinothalamic tract, medial longitudinal fasciculus, central tegmental tract, corticospinal tract and transverse pontine fibres, were identified on PADRE imaging. PADRE imaging from MSA-C demonstrated the disappearance of transverse pontine fibres and significant atrophy of the inferior cerebellar peduncles, while the superior cerebellar peduncles were intact. PADRE imaging also demonstrated that the transverse pontine fibres and inferior cerebellar peduncle were not involved in the other neurodegenerative diseases.ConclusionPADRE imaging can offer a new form of tract imaging of the brainstem and may have the potential to reinforce the clinical utility of MRI in differentiating MSA from other conditions.

Early and late inhibition in the human motor cortex studied by paired stimulation through subdural electrodes

OBJECTIVES To evaluate the focal nature of the early and late inhibition of corticospinal neurons demonstrated by a paired-pulse stimulation paradigm. METHODS We performed paired-electric pulse stimulation studies using subdural electrodes implanted in 4 patients with intractable partial epilepsy. RESULTS Inhibition of motor evoked potentials in the first dorsal interosseous muscle was obtained by paired-pulse stimulation of the hand motor cortex (M1) with a subthreshold conditioning stimulus at conditioning-test intervals between 1 and 6ms. This early inhibition was abolished when the conditioning stimulus was moved to the sensory cortex (S1) or the arm M1. The inhibition was also produced by paired-pulse stimulation of the hand M1 with a suprathreshold conditioning stimulus between 50 and 300ms in all 3 patients. This late inhibition was still recognized when moving the conditioning stimulus to the hand S1 only in one of 3 patients. CONCLUSIONS The early inhibition arises from very small areas in the M1 and is little mediated by neuronal circuits in the S1. On the other hand, the focal nature of the late inhibition is complicated and it arises mainly from the M1 but the S1 may be related to the generation of the late inhibition in some cases.

Sympathetic skin responses recorded from non-palmar and non-plantar skin sites : their role in the evaluation of thermal sweating

OBJECTIVE To characterize the sympathetic skin responses (SSRs) recorded from non-palmar and non-plantar (non-Pa/P1) skin sites and to evaluate their clinical usefulness. METHODS SSRs were recorded from 6 non-Pa/P1 sites as well as palmar and plantar (Pa/P1) sites using magnetic neck stimulation in 33 normal subjects, 17 neurological patients with dysautonomia and one patient with lumbar sympathectomy. A conventional thermoregulatory sweat test (TST) was also carried out in 3 patients. RESULTS Clear and reproducible SSRs were obtained from all recording sites in all of the normal subjects when the skin temperatures of the subjects were maintained above 34 degrees C and the subjects drank 100-200 ml of hot water. The distribution of absent SSRs was closely correlated with that of anhidrosis or a sweating delay shown by the TST in the patients. Nine of the 17 neurological patients (53%) showed normal responses at Pa/P1 sites, and abnormal responses at non-Pa/P1 sites. CONCLUSIONS Recording SSRs from multiple skin sites including non-Pa/P1 sites after magnetic stimulation is more sensitive in detecting sudomotor dysfunction than is the conventional method of recording SSRs from only Pa/P1 sites. In addition, this new method is very useful for the objective clinical evaluation of thermal sweating.

Cerebellar stimulation in acute cerebellar ataxia.

OBJECTIVES To report follow-up studies of cerebellar stimulation in patients with acute cerebellar ataxia (ACA). METHODS We studied two patients with ACA. One patient also had decreased deep sensations in the feet due to combined diseases such as diabetic polyneuropathy and lumbosacral radiculopathies. We applied the technique of electrical stimulation over the cerebellum which was reported previously (Ugawa et al., J Physiol 441 (1991a) 57). RESULTS Conditioning stimulation over the cerebellum did not reduce the size of motor-evoked potentials to test magnetic stimulation of the motor cortex at conditioning-test intervals of 5, 6, and 7 ms in the acute stage in both patients. However, normal suppression was recognized in the recovery stage in both patients. CONCLUSIONS This technique was useful for follow-up evaluation of cerebellar function in patients with ACA and was also useful for distinguishing cerebellar ataxia from sensory ataxia in a patient with combined diseases.

An adult form of Alexander disease: a novel mutation in glial fibrillary acidic protein

Glial fibrillary acidic protein (GFAP) mutation has been reported in Alexander disease. We report a patient with the adult form of Alexander disease who shows a novel mutation in GFAP. This case presented with progressive dysarthria, dysphagia and spastic gait on the right side. Brain and spinal cord MRI showed marked atrophy of the medulla oblongata and spinal cord. Abnormal high signal intensities in the ventral medulla oblongata were detected bilaterally. There were no white matter lesions or contrast enhancing lesions. Recently, there have been reports of patients with a juvenile form of Alexander disease presenting with atrophy or signal abnormalities of the medulla or spinal cord. Atrophy of the medulla and spinal cord have specifically been described as suggestive of Alexander disease [1]. Sequence analysis of the GFAP gene of this patient showed a heterozygous c.221T>C mutation, predicting a p.M74T amino acid change. In all patients suspected of Alexander disease on the basis of MRI findings, GFAP analysis is necessary to confirm the diagnosis.