[Convulsive syncope then convulsive seizure occurred in the long clinical course: a case report].

A 17-year-old woman presented with transient consciousness impairment attack and convulsion after bathing and prolonged standing since age 12. EEG showed WHAM ( wake, high amplitude, anterior, male) type of phantom spikes that usually carry the high risk of epilepsy at age 13. At age 17, EEG wise generalized spike and wave complex was recorded once, and head-up tilt test was positive. She was carefully observed without antiepileptic drugs since convulsive syncope due to neurally mediated syncope was most likely. During the follow-up period, she had eventually unprovoked generalized tonic-clonic seizures (convulsive seizure) twice and thus she was started with antiepileptic drug with success. Although both convulsive syncope and convulsive seizure differ in nature and effects on quality of life, in this patient, the latter occurred later and both occurs together. It is important to distinguish them by means of the degree of convulsion and EEG finding.

Scalp EEG Could Record Both Ictal Direct Current Shift and High-Frequency Oscillation Together Even With a Time Constant of 2 Seconds.

Herein, the authors report for the first time, scalp-recorded (1) focal ictal direct current (DC) shifts (active DC shifts; that precede conventional pattern) from the chronic focus of focal epilepsy and (2) ictal high-frequency oscillation after ictal DC shifts (passive DC shifts; that follow both conventional and high-frequency oscillation ictal patterns) from the acute focus of acute symptomatic seizures (Szs) in a 77-year-old man. Sixteen episodes of clinical Szs were recorded by scalp EEG with a 2-seconds time constant. Among the 16 recorded episodes of Sz, four EEG Sz patterns originated from the left posterior temporal area (chronic focus), and all patterns (100%) exhibited active DC shifts preceding the conventional pattern by 12 seconds. Twelve EEG Sz patterns originated from the right parietal area (acute focus), and the high-frequency oscillations (five Szs) (41.6%) and DC shifts (six Szs) (50%) occurred first, followed by the conventional pattern 8 seconds later. Because both the active and the passive DC shifts were recorded with a time constant of 2 seconds, which was smaller than that reported previously for ictal DC shifts (e.g., time constant of 10 seconds), clinically useful ictal DC shifts could be routinely inspected with a time constant of 2 seconds.

Low-dose perampanel improves refractory cortical myoclonus by the dispersed and suppressed paroxysmal depolarization shifts in the sensorimotor cortex.

OBJECTIVE: To elucidate the effects of perampanel (PER) on refractory cortical myoclonus for dose, etiology and somatosensory-evoked potential (SEP) findings. METHODS: We examined 18 epilepsy patients with seizure and cortical myoclonus. Based on data accumulated before and after PER treatment, correlations among clinical scores in myoclonus and activities of daily life (ADL); early cortical components of SEP; and PER blood concentration, were analyzed. RESULTS: PER (mean dose: 3.2 ±â€¯2.1 mg/day) significantly improved seizures, myoclonus and ADL and significantly decreased the amplitude of and prolonged latency of giant SEP components. The degree of P25 and N33 prolongations (23.8 ±â€¯1.6 to 24.7 ±â€¯1.7 ms and 32.1 ±â€¯4.0 to 33.7 ±â€¯3.4 ms) were significantly correlated with improved ADL score (p = 0.019 and p = 0.025) and blood PER concentration (p = 0.011 and p = 0.025), respectively. CONCLUSIONS: Low-dose PER markedly improved myoclonus and ADL in patients with refractory cortical myoclonus. Our results suggest that SEP, particularly P25 latency, can be used as a potential biomarker for assessing the objective effects of PER on intractable cortical myoclonus. SIGNIFICANCE: In this study, PER lessened the degree of synchronized discharges in the postsynaptic neurons in the primary motor cortex.

[A Case of Cowden Syndrome Associated with Lhermitte-Duclos Disease].

A 24-year-old woman slowly developed mild unsteadiness of gait. Neurological examination revealed mild dysmetria of the left upper and lower limbs. Standing and gait were unsteady, and tandem gait was impossible. Cranial magnetic resonance imaging (MRI) showed an enlarged left cerebellar hemisphere with striated lines, a characteristic finding of Lhermitte-Duclos disease. She also had papules on the forehead, goiter, lactating adenoma, glycogenic acanthosis in the esophagus, café-au-lait spot, and hemangioma and keratosis on the dorsum of foot. The diagnosis of Cowden syndrome was established by finding the mutation in the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene. Cowden syndrome is an autosomal dominant disorder characterized by multiple hamartomas in a variety of tissues. Recognition of Lhermitte-Duclos disease as a neurological condition of Cowden syndrome is important, and once the diagnosis of Lhermitte-Duclos disease is made, a close physical investigation is necessary because the hamartomas tend to develop malignancies. (Received March 15, 2017; Accepted July 24, 2017; Published December 1, 2017).

A case of bulbospinal muscular atrophy with large fasciculation manifesting as spinal myoclonus.

OBJECTIVE: This paper reports a patient with bulbospinal muscular atrophy (BSMA) who presented with spinal myoclonus, documented by video and surface electromyography. CASE REPORT: A 66-year-old man had progressive gait disturbance, dysphagia, and easy fatigability of all extremities over a period of 4 years. Neurologically, muscle atrophy, fasciculation, and weakness were observed in the bulbar and limb muscles. When the knees were kept in mild flexion in the supine position, fasciculation of the thigh adductor muscles was so large that it caused shock-like involuntary movements of the legs, corresponding to spinal myoclonus. A genetic test revealed 41 repeats of CAG in the androgen receptor gene, and the diagnosis of BSMA was made. SIGNIFICANCE: The present case suggests that extremely large fasciculation can cause spinal myoclonus.

[A case of MELAS associated with histochemical findings of muscles characteristic of MERRF].

We here report a 39-year-old woman of short stature with sensorineural deafness, who suddenly developed status epilepticus. T2-weighed image of brain magnetic resonance imaging (MRI) revealed a high signal lesion in the left temporal area, the distribution of which was not compatible with any particular arterial supply. Lactate and pyruvate were elevated in the serum and cerebrospinal fluid. As the mitochondrial gene analysis revealed the m.3243A>G mutation, diagnosis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) was made. In the histochemical study of a biopsied muscle, the intramuscular blood vessels reacted strongly with SDH (SSV), but the SSV was negative for cytochrome c oxidase (COX), the findings characteristic of myoclonic epilepsy with ragged-red fibers (MERRF). This is the first case of MELAS in which the muscle histochemistry showed positive SSV unassociated with increased COX.

[A case of myasthenia gravis presenting solely with bulbar palsy unassociated with easy fatigability].

A 69-year-old Japanese female was admitted because of progressive nasal voice and dysphagia. Neurological examination revealed paresis of the soft palate with marked dysphagia and rhinolalia. Otherwise there was no weakness or easy fatigability in extraocular muscles and extremities. On laboratory test, anti-acetylcholine receptor antibody (anti-AChR Ab) was positive, while anti-muscle-specific tyrosine kinase antibody (anti-MuSK Ab) was negative. Edrophonium test was positive, resulting in clear improvement in phonation and swallowing. Harvey-Masland test of ocular and extremity muscles did not show any waning. With the diagnosis of bulbar myasthenia gravis, the patient was treated with methylprednisolone and pyridostigmine, resulting in clear improvement of the symptoms. The present case shows that it is important to consider MG even in cases presenting solely with progressive bulbar palsy without easy fatigability. So far, cases of bulbar myasthenia gravis with positive anti-MuSK Ab have often been reported. As shown in the present case, bulbar myasthenia gravis can also be associated with positive anti-ACh-R Ab but negative anti-MuSK Ab.

[Case of post-anoxic reticular reflex myoclonus].

BACKGROUND: Reticular reflex myoclonus is a rare condition with only a few cases clearly documented on video. The purpose of this paper is to report a patient manifesting typical clinical picture documented on video and characteristic electrophysiological features of reticular reflex myoclonus. CASE: A 60-year-old woman presented with spontaneous and stimulus-sensitive myoclonic jerks involving the face, neck and upper extremities following anoxic episode. The patient was investigated electrophysiologically. Surface electromyogram showed brief myoclonic activity starting from the sternocleidomastoid and spreading up to the orbicularis oculi as well as down to the upper limb muscles. Cortical somatosensory evoked potentials and long-latency reflex were not enhanced. CONCLUSION: Clinical features and electrophysiological findings of this case are consistent with those of reticular reflex myoclonus originally reported by Hallett et al. in 1977.

[Elderly case of moyamoya disease presenting with hemichorea].

A 61-year-old Japanese female was admitted with sudden onset of choreic movements of the right extremities. MRI demonstrated no abnormality suggestive of acute infarcts. Cerebral angiography revealed high-grade stenosis of bilateral middle cerebral arteries at the origin and abnormal vascular network compatible with moyamoya disease. Administration of low-dose haloperidol rapidly resolved the choreic movements. SPECT obtained one month after the clinical onset demonstrated increase of the regional cerebral blood flow (rCBF) in the left basal ganglia. Moyamoya disease presenting chorea as its initial symptom was only infrequently reported in the elderly. In the present case, increased rCBF in the basal ganglia and remarkable effect of a dopamine D2 blocker suggest functional abnormality of the corresponding striatum as an underlying cause of hemichorea.

Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy.

The clinical implications of enlarged early cortical components of somatosensory evoked potentials in benign adult familial myoclonus epilepsy remain unknown. Somatosensory evoked potentials following electrical stimulation of the median nerve at the wrist were studied in 16 patients with a clinical diagnosis of benign adult familial myoclonus epilepsy (7 men and 9 women; mean age, 51 ± 18 years) and 19 age-matched apparently healthy control subjects (11 men and 8 women; mean age, 49 ± 18 years). Giant somatosensory evoked potentials were observed in 13 of the 16 patients. P25 and N35 amplitudes in the patient group were 11.4 ± 6.1 and 19.2 ± 11.5 µV, respectively, and both were significantly larger compared with those in control subjects (P = 0.008 for P25 and P < 0.0001 for N35). There was a significant positive relationship between age at somatosensory evoked potential examination and N20, P25, and N35 amplitudes, both in the patient and in the control groups (P < 0.05). The linear regression gradient of the N35 amplitude with respect to age was significantly larger in the patient group than in the control group (P = 0.04). Furthermore, regression analysis showed a significant positive relationship between the myoclonus rating scale and age at time of somatosensory evoked potential examination (R = 0.645, P = 0.007). Somatosensory evoked potential amplitude increased with age in patients with benign adult familial myoclonus epilepsy to a greater extent than in the control subjects, which suggests a progressive increase in cortical excitability based on progressive pathophysiology in benign adult familial myoclonus epilepsy.

[A case of Bickerstaff brainstem encephalitis concomitant with axonal Guillain-Barre syndrome and ballism successfully treated with intravenous immunoglobulin treatment].

A 39-year-old man acutely developed diplopia, vertigo, unsteady gait, and disturbance of consciousness following an upper respiratory infection. Neurological examination showed ophthalmoplegia, facial paralysis, tetraplegia and loss of deep tendon reflexes. Babinski reflex was positive on the left and there were bilateral flexor withdrawal reflexes. He also developed ballism-like involuntary movements in all extremities, loss of proprioception predominantly on the left, and severe truncal ataxia. Anti-GQ1b IgG antibody was selectively elevated in serum, and CSF protein was elevated to 53 mg/dl with cell count of 12/mm3. Nerve conduction study showed decreased amplitude of compound motor action potentials in all extremities, and no response in facial muscles. Cranial MRI showed no abnormalities whereas EEG was severely abnormal with lack of posterior dominant rhythm and the presence of continuous diffuse theta-waves. This case presented clinical characteristics of three syndromes concurrently-Fisher syndrome, Bickerstaff brainstem encephalitis, and Guillain-Barré syndrome-that may be collectively called 'anti-GQ1b IgG antibody syndrome'. The unique feature of the present case was development of deep coma and ballism-like movements, associated with selective increase of serum anti-GQ1b IgG antibody. It is thus conceivable that anti-GQ1b IgG antibody might underlie the pathogenesis of all three conditions.

[Case presenting both clinical features of progressive supranuclear palsy and amyotrophic lateral sclerosis].

A 70-year-old Japanese male farmer, born and living in Kyoto prefecture, developed gait disturbance, with tendency to fall at age 68, and muscle atrophy and weakness of the right shoulder and arm a year and half later. All symptoms have been progressive ever since. The patient manifested marked dementia, parkinsonism associated with limitation of ocular movements in all directions with slow saccade, loss of startle reflex, asymmetric muscle atrophy and weakness in shoulder girdles and upper limbs with hyperreflexia, and positive Babinski reflexes. The needle electromyogram showed evidence of active denervation. Brain MRI showed cortical atrophy in the frontal and temporal lobes, and midbrain tegmentum. Cerebral blood flow image on SPECT suggested hypoperfusion in the frontal, temporal and parietal cortices and basal ganglia bilaterally. Thus, it is most likely that the present case suffered from clinical features of amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy at the same time. Relation to the ALS/Parkinsonism/Dementia complex reported from Kii peninsula and Guam was discussed.

Transcranial magnetic stimulation (TMS) of the sensorimotor cortex and medial frontal cortex modifies human pain perception.

OBJECTIVE: Although recent neuroimaging studies have shown that painful stimuli can produce activity in multiple cortical areas, the question remains as to the role of each area in particular aspects of human pain perception. To solve this problem we used transcranial magnetic stimulation (TMS) as an 'interference approach' tool to test the consequence on pain perception of disrupting activity in several areas of cortex known to be activated by painful input. METHODS: Weak CO(2) laser stimuli at an intensity around the threshold for pain were given to the dorsum of the left hand in 9 normal subjects. At variable delays (50, 150, 250, 350 ms) after the onset of the laser stimulus, pairs of TMS pulses (dTMS: interpulse interval of 50 ms, and stimulus intensity of 120% resting motor threshold) were applied in separate blocks of trials over either the right sensorimotor cortex (SMI), midline occipital cortex (OCC), second somatosensory cortex (SII), or medial frontal cortex (MFC). Subjects were instructed to judge whether or not the stimulus was painful and to point to the stimulated spot on a drawing of subject's hand. RESULTS: Subjects judged that the stimulus was painful on more trials than control when dTMS was delivered over SMI at 150-200 ms after the laser stimulus; the opposite occurred when dTMS was delivered over MFC at 50-100 ms. dTMS over the SII or OCC failed to alter the pain threshold. CONCLUSIONS: These results suggest that TMS to SMI can facilitate whereas stimulation over MFC suppresses central processing of pain perception. Since there was no effect of dTMS at any of the scalp sites on the localization task, the cortical locus for point localization of pain may be different from that for perception of pain intensity or may involve a more complex mechanism than the latter. SIGNIFICANCE: This is the first report that TMS of SMI facilitates while that of MFC suppresses the central processing of pain perception. This raises the possibility of using TMS as a therapeutic device to control pain.

Amyotrophic lateral sclerosis with IgM antibody against gangliosides GM2 and GD2.

We report a case of amyotrophic lateral sclerosis (ALS) with IgM antibody against gangliosides GM2 and GD2. A 57-year-old woman presented with slowly progressive muscular weakness of the upper extremities and dysarthria. She fulfilled the clinical and electrophysiological criteria of ALS, and died from sudden suffocation about 3 years after the onset of illness. The patient's serum IgM antibody was shown to recognize the structure shared by GM2 and GD2. Since anti-GM2 antibodies have been implicated in motor neuropathy or motor neuron syndrome, this rare case might contribute to the understanding of the immunological aspects of ALS.

Functional and morphological changes in the hippocampal neuronal circuits associated with epileptic seizures.

PURPOSE: We review what is currently known about functional and morphologic plasticity of hippocampal neuronal circuits in animal epilepsy models. RESULTS: Perforant-path kindling has been shown to enhance excitatory synaptic transmission in the dentate gyrus significantly, and this enhancement has lasted for > or =1 month after kindling. However, in our rapid kindling experiment with an interstimulus interval of 5 min, perforant-path kindling resulted in behavioral convulsions and prolonged the afterdischarge duration, but dentate synaptic transmission remained depressed during kindling. CONCLUSIONS: These results indicate that kindling-induced synaptic potentiation is not necessary for kindling development. Conversely, epileptic seizures have led to the anomalous sprouting of mossy fibers, a process thought to induce hyperexcitation of granule cells. We conclude that the sprouting of mossy fibers did not play a critical role in kindling, because we observed no significant correlation between the mossy fiber sprouting and kindling development. Epileptic seizures also have been shown to increase gamma-aminobutyric acid (GABA)A receptor-mediated inhibition during interictal periods. Although this strengthening of GABAergic inhibition is likely to be a defensive measure against seizure initiation, some studies have suggested that another type of GABAergic response facilitates seizure activity. The possibility of GABAA receptor-mediated excitation during ictal periods is theoretically examined.

Cortical potentials related to assessment of pain intensity with visual analogue scale (VAS).

OBJECTIVES: To elucidate brain mechanisms underlying the psychophysical processes to measure pain intensity, pain-related somatosensory evoked potentials (pain SEPs) following painful CO(2) laser stimulation were studied while employing a task to measure intensity of pain on a visual analogue scale (VAS). METHODS: In 12 healthy subjects, 3 kinds of CO(2) laser stimuli, different in intensity as determined by irradiation duration of 40, 60 and 80ms, were randomly delivered to the left hand dorsum at an irregular interval of 4-6s. The subject was requested to assess the intensity of each pain stimulus and point to the VAS scale by moving a pointer held with the right hand according to the subjective feeling of pain sensation (pain intensity assessment (PIA) condition). For the control condition, the subject moved the pointer to the midpoint of the VAS line irrespective of the pain intensity (control motor task condition). Electroencephalograms were recorded from 21 scalp electrodes, referenced to the linked earlobes, and were averaged time-locked to the stimulus onset for each stimulus duration as well as for each task condition. RESULTS: The VAS scores were 2.8+/-0.5/10 for the stimulus of 40ms duration, 4.8+/-0.8/10 for 60ms and 6.1+/-0.9/10 for 80ms, and showed a highly significant positive correlation with the stimulus duration. Following the early components of pain SEPs which were affected by stimulus duration but not modulated by task conditions, a surface-positive peak at latency of 612-642ms was identified exclusively under the PIA condition regardless of the stimulus intensity and was called 'intensity assessment-related potential (IAP)'. The IAP was maximal at the midline parietal area and symmetrically distributed over the scalp. Neither latency nor amplitude of the IAP was significantly different among the 3 different stimulus intensities. CONCLUSIONS: IAP is an event-related potential (ERP) associated with assessment of pain intensity but not influenced by pain intensity itself. From its scalp distribution, it can be assumed that the assessment of pain intensity involves multiple areas in both hemispheres.