Identification of a negative bitemporal component (N300) of the event-related potentials demonstrated by noncephalic recordings.

We studied the scalp distribution of auditory event-related potentials (P300), using simultaneously a cephalic (linked ears) and a noncephalic (balanced sternovertebra) reference. The recordings with noncephalic reference showed that infrequent, attended auditory stimuli evoke a negative bitemporal component (N300) as well as a positive vertex component (P300).

Cortical excitability after myoclonus: jerk-locked somatosensory evoked potentials.

Cortical excitability after myoclonus was investigated by electrically stimulating the median nerve just at the time of, or at intervals after, the onset of myoclonus and by averaging the EEG and EMG, using the myoclonus onset pulse as a trigger (jerk-locked somatosensory evoked potential technique). In a patient with "cortical reflex" myoclonus, cortical excitability was relatively enhanced for 20 msec just after the myoclonus, although it was suppressed throughout the postmyoclonus period. In a patient with Creutzfeldt-Jakob disease, cortical excitability was suppressed between periodic myoclonic jerks. In a patient with oculopalatal-somatic myoclonus, there was no change of cortical excitability in relation to myoclonus.

Accelerated aging of the brain in Werner's syndrome.

We report the electrophysiologic examination of a 55-year-old woman with Werner's syndrome. Needle EMG and peripheral conduction studies were normal. In contrast, EEG was moderately abnormal, the N20 and P25 potentials of SEPs were delayed and enlarged, and the event-related potential, P300, was delayed. These characteristic findings indicated accelerated aging of the brain, as in the other organs, in Werner's syndrome.

Neuroepithelial cyst presenting as recurrent aseptic meningitis.

A 41-year-old man had three episodes of acute aseptic meningitis from the age of thirty-six. With each episode he had severe occipital headache associated with a mononuclear pleocytosis and an increase in CSF protein. He had a neuroepithelial cyst originating from the choroid plexus of the right cerebellomedullary cistern. Spontaneous ruptures of the cyst probably caused recurrent chemical meningitis. A neuroepithelial cyst must be considered in the differential diagnosis of intracranial cystic tumors presenting with aseptic meningitis.

Numb chin syndrome secondary to Burkitt's cell acute leukemia.

We describe a case of Burkitt's cell acute lymphoblastic leukemia presenting with the bilateral numb chin syndrome as the initial symptom of the disease. Postmortem study of the trigeminal nerve showed heavy infiltrations of leukemic cells and destruction of axon and myelin by leukemic cells in the mandibular nerve.

Cortical tremor: a variant of cortical reflex myoclonus.

Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

Genetic analysis enables definite and rapid diagnosis of cerebrotendinous xanthomatosis.

Mutations in the sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis (CTX). Early diagnosis of CTX is crucial because treatment with chenodeoxycholic acid can prevent or reverse some of the neurologic disability associated with the disease. We report the identification of three types of mutations (Arg441Trp, Arg372Gln, and Arg441Gln) in the CYP27 gene in five patients with suspected CTX from four unrelated families by restriction endonuclease analysis.

Volitional movement is not preceded by cortical slow negativity in cerebellar dentate lesion in man.

Slow negative potential preceding voluntary self-paced middle finger extension, as recorded from scalp electrodes by backward averaging technique, was absent in two patients with dyssynergia cerebellaris myoclonica (Ramsay Hunt syndrome); but present in two patients with cerebellar cortical degeneration. As the main pathological lesion in Ramsay Hunt syndrome is in the dentate nucleus and its efferent pathway, the present results are in conformity with the experimental finding that the premotor and motor cortices receive strong inputs from the cerebellar efferent system.

Treatment of HTLV-I-associated myelopathy with high-dose intravenous gammaglobulin.

Fourteen patients with HTLV-1-associated myelopathy were treated with high-dose intravenous gammaglobulin (IVGG). Ten received 10 g/day of IVGG and 4 received 400 mg/kg of body-weight/day of IVGG for 5 consecutive days. Improvement of spastic paraparesis was observed in 10 within 7 days of the commencement of IVGG. The therapeutic effects were sustained for more than 3 weeks in some patients. There were no side effects. Analysis of factors of relevance to the clinical improvement with IVGG showed that the beneficial response was preferentially found in patients having a high CSF titre of anti-HTLV-I antibodies, a high CSF IgG level and a marked brain MRI abnormality.

Do patients with Down's syndrome recognize Mickey Mouse?

In 47 patients with Down's syndrome who were too retarded to understand a conventional oddball paradigm, we studied event-related potentials (ERPs) by using task-irrelevant visual stimuli. As the patients had expressed interest in Disney cartoons and books, five pictures of Disney characters such as Mickey Mouse or Peter Pan were employed as the rare stimuli, and nine ordinary scenes such as mountains as the frequent stimuli. Five sets were constructed by intermingling each rare picture with nine frequent pictures, and each picture was presented on a TV screen. ERPs to the rare stimuli (N270-P380), which were different from the averaged waveforms to frequent stimuli and electrooculograms (EOGs), were clearly recorded in 35 out of 47 patients. Only 24 of these patients had ERPs using a conventional auditory oddball paradigm. The peak latencies in patients were significantly prolonged relative to age-matched normal controls, probably due to a slowed neural processing. The amplitude in patients was slightly larger than normal controls, probably due to the patients' greater interest or surprise when confronted with the Disney characters.

Physiological study of the spinothalamic tract conduction in multiple sclerosis.

This is the first paper to study the physiological function of the spinothalamic tract in multiple sclerosis (MS) using pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation. Among 12 patients with MS, hand- and foot-stimulated pain SEPs were significantly delayed or absent in 3 and 7, respectively. These results were totally consistent with clinical impairment of pain-temperature sensation. In contrast, the results of conventional electrically-stimulated SEPs were compatible with impairment of vibration sensation. Therefore, the examination of both pain and electric SEPs is very useful to evaluate the physiological function of the ascending spinal tract in patients with MS.

Recording of event-related potentials (P300) from human cortex.

Auditory event-related potentials were recorded simultaneously from chronically implanted subdural electrodes and from scalp electrodes in three patients who were being evaluated for surgical treatment of epilepsy. These three cases showed clearly defined scalp-P300 and scalp-N300. A cortex-P300 was recorded from the midtemporal area, and a cortex-N300 was recorded from the inferior frontal area with some reflection at the basal temporal region. There were no potentials from an interhemispheric region. We could not observe any component from the cortex studied corresponding to scalp-recorded N200. Therefore, while the activity generated from the mesial temporal lobe may only make minor contributions to scalp-P300, that generated from the midtemporal area might make a major contribution to the scalp-P300. Additionally, generators of N200, P300, and N300 are different from each other. These findings, together with previous reports regarding the generator source of P300, also suggest that P300 is a complex arising from multifactorial generator sources, including the midtemporal and inferior frontal area.

Electroencephalographic correlates of myoclonus.

Fifty-five consecutive cases of myoclonus owing to various etiologies were studied by conventional EEG-EMG polygraphic recordings and/or jerk-locked or back averaging. The technique of back-averaging was shown to be useful not only for detecting EEG correlates of myoclonus that are not recognizable on the routine polygraph but also for investigating the temporal and topographic relationship between the EEG activities and myoclonus. Thirteen of 17 cases of PME and related disorders, in whom back-averaging and SEP were studied, were shown to have both a myoclonus-related cortical spike over the contralateral central area, preceding the myoclonus of an upper extremity by 6 to 22 msec, and a giant SEP accompanied by an enhanced C reflex. In these cases of "cortical reflex myoclonus," the myoclonus-related spike was similar to the P25-N33 components of the giant SEP in its wave form, scalp topography, temporal relationship to myoclonus or to C reflex, succeeding cortical excitability, and drug effect. All of this suggests participation of common physiological mechanisms in those two activities. In two cases of PME, in which myoclonus involved bilateral proximal muscles synchronously, the myoclonus-related spike was maximal near the vertex, and there was no giant SEP. The significance of this subgroup remains undetermined. In six cases of the PME group, back-averaging was inapplicable because of rare occurrence of myoclonus, but they showed a typical giant SEP accompanied by an enhanced C reflex. In CJD, back-averaging demonstrated a sharp wave or PSD over the contralateral hemisphere, preceding the myoclonus by 50 to 85 msec. This form of myoclonus seems to be subcortical in origin. In essential myoclonus and oculopalatal-somatic myoclonus, there was neither myoclonus-related cortical spike nor giant SEP. Electrical stimulation of the peripheral nerve at variable intervals after the myoclonus onset (jerk-locked-SEP paradigm) was shown to be useful for investigating the influence of myoclonus on cortical excitability.

A method for real-time processing to study recovery functions of evoked potentials.

A new method for evaluating the recovery function of evoked potential (EP) in real time was reported. To record the test response of paired stimulation, the responses to alternate presentation of unpaired stimulus and several kinds of paired stimuli with various interstimulus intervals were averaged respectively and subtraction was made in real time. The EP's to the test stimulus obtained by the proposed method were proved to be accurate even under the changing recording conditions. A formula for computing the recovery correlation factor was derived as a measure of the recovery function of the recorded EP, and the recovery curves for three subjects were obtained.

Event-related brain potentials as indicators of visual recognition and detection of criminals by their use.

An event-related potential (ERP) was recorded, using photographs as stimuli, in 12 subjects for attended, 9 subjects for non-attended conditions and 14 subjects for a simulated criminal investigation. An ERP was detected only when a subject recognized a familiar image (target) mixed with other, unfamiliar images (non-target), regardless of whether he was asked to attend to or neglect the target image. ERPs in the subject who watched each picture but tried to ignore the relevant picture (non-attended) were more activated at the parietal region than at the central region, in contrast with ERPs in the subjects who paid attention to each picture without trying to ignore the relevant picture (attended). In the simulated criminal investigation, only a simulated thief, but not a simulated innocent subject elicited ERP only after the picture of a criminal site or thing was intermingled with pictures bearing no relationship to the crime. These findings indicate that the ERP using photographs as stimuli is useful as an objective indicator of crime-relevance.

[A case of Prader-Willi syndrome with bilateral middle cerebral artery occlusion and moyamoya phenomenon].

We report a case of Prader-Willi syndrome (PWS) complicated with juvenile stroke. The patient is a 19-year-old man with right hemiplegia, who has had a history of non-insulin-dependent diabetes mellitus (NIDDM) for ten years. The diagnosis of PWS was confirmed genetically by the method of fluorescence in situ hybridization which showed the deletion of chromosome 15. His brain MRI revealed abnormal signal intensities in the left basal ganglia and around the right trigone of the lateral ventricle. Angiographic examination showed occlusions of bilateral proximal middle cerebral arteries with basal moyamoya vessels. The left vertebral artery was also occluded at its origin. Only a few cases of PWS complicated with stroke have been reported before and, to date, there has been no case with arterial occlusion similar to our case. Though the cause of these arterial occlusions is unknown, it may be related to arteriosclerosis following NIDDM.

[A case of upper brainstem infarction developing symptomatic narcolepsy after the administration of anti-convulsant drugs].

A 52-year-old woman, who had ischemic infarction in the ventral upper brainstem due to subarachnoid hemorrhage in October 1986, had recurrent sleep and cataplexy attacks from May 1987. She was receiving valproate and phenytoin daily since 1986. The diagnosis of narcolepsy was made based on the clinical symptoms and EEG findings showing REM sleep during a sleep attack. Both sleep and cataplexy attack increased in parallel with an increase of the dose of anti-convulsant drugs and disappeared immediately after the discontinuation of the treatment. The findings that suggest that the administration of anti-convulsant drug as well as the brainstem vascular lesion was deeply involved in the development of narcolepsy in this case.

[Treatment of HTLV-I-associated myelopathy with alpha-interferon and high-dose of gamma-globulin].

We administered alpha-interferon (alpha-IFN) and gamma-globulin (gamma-gl) to patients with HTLV-I-associated myelopathy (HAM). Patients selected for this study fulfilled the diagnostic criteria of HAM by Osame et al. As for alpha-IFN, 12 patients were injected intramuscularly with a dose of 3 X 10(6) IU/day of alpha-IFN for 28 days. As for gamma-gl, 10 patients were injected intravenously with a dose of 10 g/day of human gamma-gl for 5 days. alpha-IFN exerted therapeutic effects in 7 of 12 patients and gamma-gl in 6 of 10. The therapeutic effects were shown by the improvement in time for a 20-meter walk, muscle power of lower limbs and urinary frequency. All patients having a history of improvement by corticosteroid therapy showed beneficial responses to both treatments with alpha-IFN and gamma-gl. Contrarily, patients who had not improved by corticosteroid therapy did not show any improvement after gamma-gl and alpha-IFN administration. The therapeutic effects of gamma-gl and alpha-IFN were observed predominantly in cases with shorter duration of illness, more marked abnormality in cerebral MRI findings and higher CSF antibody titers to HTLV-I. There was no correlation between the therapeutic efficacy and clinical severity or serum antibody titers to HTLV-I. We conclude that therapies with alpha-IFN and gamma-gl were safe and effective for the treatment of HAM.

[A case of adult-onset spike-wave stupor associated with hypoparathyroidism and hyperostosis frontalis interna (HFI)].

A 34-year-old women without history of seizures was admitted to our hospital because of the diminished responsiveness and the repeated blinking for two days. Her past history showed neither surgery nor inflammation of the thyroid gland. General physical examination was normal. On neurological examination, the patient was blinking frequently and staring without any responsiveness. However, she occasionally became able to respond correctly to verbal orders, such as "open your eyes", "open your mouth", "stand up" and so on, which occurred abruptly just like the switch-on. She was otherwise normal neurologically. The laboratory data showed hypocalcemia, hyperphosphatemia, decreased level of parathyroid hormone and normal renal function, indicating the presence of idiopathic hypoparathyroidism. EEG showed the continuous generalized 2-4 Hz spike and wave complexes with the maximum intensity on frontal lobes. Skull roentgenograms and MRI CT of the head disclosed hyperostosis frontalis interna (HFI) and the compression of superior medial frontal lobes by the HIF. SPECT also showed the diminished circulation and hypometabolism in the superior frontal lobes. Based on clinical and EEG findings, the diagnosis of spike-wave stupor was made. She was successfully treated with valproic acid and ethosuximide. Spike and wave complexes on EEG completely disappeared after administration of alfacalcidole. It is assumed that both hypoparathyroidism and HFI were deeply involved in the development of spike-wave stupor in this adult case.

[New protocol for memory-related potential].

A new P300 testing protocol for evaluating memory function is proposed. Four stimuli (S1, S2, S3 and S4) are presented to the subject at 1.5 sec intervals and the subject is instructed to judge whether S4 was the same (80%) or not (20%) as S1, as well as whether S3 was the same (80%) or not (20%) as S2. The S2-S3 comparison acts as an attention shifting mechanism, and by inserting this comparison between S1 and S4, the subject must memorized S1 at the memory site in the brain until S4 is presented. This protocol was performed using both auditory and visual stimulations with 24 college students (age range: 19-28 years old) and a patient (23 years old) with bilateral medial temporal lobe lesions caused by limbic encephalitis. The P300 brain potentials after S3 and S4 were compared. The Wechsler memory scale-revised (WMS-R) test was also assessed in all subjects. The latency of P300 after S4 had a significantly (p < 0.01) longer than that after S3. The latency of P300 after S4 in the patient, who showed the severe auditory as well as the mild visual memory impairment, was longer than the mean + 2 SD in the normal subjects for auditory stimuli, but not for visual stimuli, whereas the latency of P300 after S3 in the patient was longer than the mean + 2 SD in the normal subjects only for visual stimuli. The brain potential after S4 might be more reflective of a degree of memory disorder as compared with that after S3. Furthermore, the latency of P300 after S4 showed a more significant correlation with some WMS-R scores (verbal memory, general memory and verbal delay) than the latency of P300 after S3. These results suggest that measuring the P300 latency after attention shifting in the new protocol is useful for the evaluation of memory functions.