This is a case report that describes 2 sisters with microcephaly, simplified gyri, and enlarged extraaxial space. Clinical features of the cases include dysmorphic features, congenital microcephaly, failure of postnatal brain growth, neonatal onset of seizures, quadriplegia, and severe psychomotor delay. Neuroradiological imaging demonstrated hypoplasia of bilateral cerebral hemispheres with enlarged extraaxial spaces, simplified gyral patterns without a thickened cortex, hypoplastic corpus callosum, and enlarged lateral ventricles, with a reduction in gray and white matter volume during the prenatal and neonatal periods. Repeat MRI revealed progressive atrophy of the cerebral gray and white matter, with enlarged lateral ventricles, although the sizes of the bilateral basal ganglia, thalamus, and infratentorial structures were relatively preserved. These neuroradiological findings imply that this disease is caused by the gene involved in neuronal and glial proliferation in the ventricular zone and in tangential neuronal migration from the ganglionic eminence. The nature of the progressive degeneration of the hemispheric structures should be clarified.

In the history, function of the Human body has been expanded with various vehicles like automobile, ship and plane, so exercise of the human body was tended to decrease by the vehicle, unfortunately. However, if the information of human body will be detected by the motor car and several kinds of intervention was added to the body, the automobile can become the treatment system. Several investigators have been studying about the man-machine interface.□@In this study, we added the diagnosis and therapeutic effect for the autonomic nervous system during driving. ECG recording system and pulse wave recording system was added to the handle and drive console in the experimental system. Air pressure sensors to detect the respiration and aortic pulse wave were inserted into the drive seat. By the evaluation of the ECG and pulse wave, we can evaluate the circulation dynamics. Furthermore, we can evaluate the pulse wave velocity, so, blood pressure was calculated from each driver data base. And fluctuations and baroreflex sensitivity were also calculated. By the use of the information, several kinds of Aroma, Massage to the Acu-points or the automatic Moxibustion will be added to the driver. So, the automobile can control the hemodynamics and autonomic nerve condition during driving (Jpn.Pt.Appl.2009-326215). After ethical committee allowance, we evaluated the effect of aroma therapy and acu point stimulation on driver during drive simulation and recognition tests by the use of the healthy adult male volunteers. Hemodynamics, HRV and baroreflex sensitivity were tended to altered depending of the kinds of Aroma and stimulation to the several kinds of acupoints, sugesting the effect of alternative treatment to the driver. So, baroreflex system may be contollable during driving by alternative medical treatment. Furthermore, the Arousal and driving behavior were tended to altered by the alternative therapeutic intervention. These results suggest that automobile can become diagnosis and treatment machine to prevent hypertension.

We investigated the effects of histamine H1 antagonists on acutely dissociated neurons from the rat cortex using the patch-clamp technique. First-generation antihistamines, such as pyrilamine, d-chlorpheniramine, diphenhydramine, and ketotifen, suppressed M-currents in a concentration-dependent manner with respective half-inhibition concentrations (C50) of 35.9, 48.5, 34.8, and 47.8 microM at a holding potential of -26.5 mV. Astemizole, a second-generation antihistamine, inhibited M-currents with a C50 of 18.1 microM, but cetirizine did not do so, up to a concentration of 300 microM. Neither ranitidine nor cimetidine, both H2 antagonists, suppressed M-currents. The C50 of pyrilamine significantly decreased with membrane hyperpolarization, suggesting that it acts directly on M channel pores. The inhibition of M channels may be involved in the neurotoxic effects of histamine H1 antagonist overdose.

We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy (1H-MRS). The single-voxel 1H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of −3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of −1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.

An 11-year-old boy presented with acute dysautonomia manifesting as severe orthostatic hypotension following fever. Serial orthostatic tests with measurement of the coefficient of variation in the R–R intervals showed improvement after one course and complete recovery after two courses of intravenous high-dose immunoglobulin therapy (IVIg). Repeated courses of IVIg should be considered to treat this disorder if spontaneous remission does not occur.

Purpose: To investigate spatial and temporal cortical activity during clusters of naturally occurring epileptic spasms in patients with West syndrome (WS) by using multichannel near-infrared spectroscopy (mNIRS).Methods: Conventional magnetic resonance imaging (MRI) and interictal and ictal single-photon emission computed tomography (SPECT) were carried out in three patients with WS. Thereafter, cortical hemodynamics during naturally occurring epileptic spasms were measured by mNIRS with simultaneous video/electroencephalographic (EEG) monitoring.Results: Ictal SPECT revealed multiple hyperperfused areas within the cortex. With the use of mNIRS, an increase in regional cerebral blood volume (CBV) was observed in these areas, which is representative of cortical activation. The increase in CBV was accompanied by an increase in the concentrations of both oxy- and deoxyhemoglobin. The following heterogeneous regional changes in CBV during ictus were observed: (a) transient increases that were synchronized with spasms; (b) a gradual increase during an ictal event that fluctuated in synchrony with spasms; and (c) a combination of transient and gradual increases. An increase in regional CBV occurred in multiple areas that were activated either simultaneously or sequentially during an ictal event. Topographic changes in CBV were closely correlated with the phenotype of the spasm.Conclusions: During ictal events, multiple cortical areas were activated Simultaneously or sequentially. The pattern of cortical activation closely affected the phenotype of the spasm, which suggested that the cortex was involved in the generation of spasms.

The anticonvulsive effect of melatonin has been reported clinically and experimentally. 1, 2 However, most of clinical reports are based on relatively low dose administration (3-10mg/day) and small number of patients. We applied high dose melatonin therapy for treatment of extremely intractable epilepsy in childhood in order to evaluate its clinical efficacy. Twelve patients of 2 to 19 years old were enrolled in this study. Among 10 patients who were classified as secondary generalized epilepsy, 8 had West syndrome in infancy and their seizures had not been controlled since then. Two patients were classified as cryptogenic localization-related epilepsy. All patients had daily seizures in spite of intensive treatment with various antiepileptic drugs, and had severe mental retardation. Five patients had abnormal sleep-wake cycle. After receiving written informed consent from the parents and an approval of local ethical committee, melatonin was added to the baseline anti-epileptic drugs with gradual increase to about 1 mg/kg/day (10 mg to 40mg/ day), taken once every night. Seizure frequency and side effects were monitored. Period of high dose melatonin therapy ranged from 17 days to 90 days. Seizure frequency during high dose melatonin was compared with the same period before melatonin administration. More than 50% decrease in seizure frequency was taken as significant response. Two patients showed complete seizure disappearance with malatonin administration. One patient with infantile spasms showed complete disappearance of spasms and hypsarrhythmia at 1 mg/kg/day. She started walking alone, and her irregular sleep-wake cycle improved significantly. However, spasms re-appeared one months later and EEG showed worsening. In another patient with localizationrelated epilepsy, seizures completely disappeared after increasing the dose to 1 mg/kg/day, with seizure free period lasted more than 12 months. However, there was no significant improvement of EEG which showed multi-focal spike. Three other patients showed partial decrease in seizure frequency of >50%. Among them one patient had transient decrease that lasted for 2 months. Decrease in seizure frequency seen in these patients was associated with an improvement of abnormal sleep-wake cycle. There were no serious side effects and no abnormal laboratory tests including liver and kidney functions. Three patients showed somnolence in the morning or daytime. High dose melatonin may be considered as an alternative choice of treatment for extremely intractable epilepsy, since 5 out of 12 patients (42%) responded partially after administration of melatonin and there were no serious side effects. Patients with abnormal sleep-wake cycle may be particularly good candidate for the melatonin add-on therapy. However, habituation of anti-convulsive effect may be a significant drawback. Double blind controlled study is needed for better evaluation of the treatment. References

Summary: Purpose: To assess the biochemical properties of band heterotopia in comparison with other cortical developmental malformations (CDMs) by using proton magnetic resonance spectroscopy ( 1 H‐MRS). Methods: We performed localized single‐voxel 1 H‐MRS studies on 13 patients [five band heterotopia (BH), two focal cortical dysplasia (CD), two unilateral CD, one bilateral perisylvian dysplasia, three hemimegalencephaly]. CDMs other than BH were categorized as CD. Spectra were acquired from volumes of interest (VOIs) localized in the CD and in normal‐appearing cortex on the contralateral side. In BH patients, the VOIs were the external cortex and the laminar heterotopia. For the BH study, spectra also were obtained from the cortex of age‐matched normal volunteers. Results: The spectra of CD lesions were characterized by significantly lower ratios of N ‐acetyl aspartate to creatine (NAA/Cr) and by higher choline to Cr (Cho/Cr) ratios than in the contralateral remote cortex (p = 0.01 and 0.01, respectively). The NAA/Cr and Cho/Cr ratios of the external cortex of BH were not significantly different from those of normal volunteers. The NAA/Cr ratio of the laminar heterotopia was not significantly different from that of the external cortex (p = 0.12) or normal volunteers (p = 0.60), whereas Cho/Cr was significantly higher in laminar heterotopias than in the external cortex (p = 0.04) or controls (p = 0.03). Conclusions: 1 H‐MRS can distinguish between the metabolic properties of BH and CD.

The clinical significance of the pressor response triggered by blood pressure measurement, the so-called "white-coat effect," was studied in relation to left ventricular structure and function in patients with essential hypertension. We studied 75 consecutive, never-before treated patients with essential hypertension (54 +/- 2 (SE) years; 31 men). Beat-to-beat blood pressure (Finapres) was monitored at rest, during conventional blood pressure measurement by a doctor, and during a mental stress test. The left ventricular mass index and diastolic function (EIA ratio) were determined by echocardiography. The systolic blood pressure response triggered by the doctor's visit (deltaSBP) correlated positively with the left ventricular mass index (r= 0.326, p<0.03) and negatively with the EIA ratio (r=-0.325, p<0.02). A positive relationship between the deltaSBP and left ventricular mass index was observed in men (r=0.556, p<0.01) but not in women. The greater ASBP also was associated with lower EIA ratio in women (r=-0.434, p<0.02). The deltaSBP correlated with the mental stress-induced increase in systolic blood pressure in men (r=0.586, p<0.005) but not in women (r=0.148, n.s.). Blood pressures outside the clinic were higher in men than in women (p<0.05 for systolic and p<0.005 for diastolic) despite the similar level of clinic blood pressures between the sexes. Stepwise multiple linear regression analysis showed that the deltaSBP was an independent predictor of the left ventricular mass index in men (beta=0.783, p=0.0009) and of the EIA ratio in women (beta=-0.003, p=0.05). These data suggest that the pressor response triggered by a doctor's visit has clinical significance in never-before treated hypertensive patients, possibly because it mirrors real-life stress reactivity in men.

Potassium bromide was tried for two children with daily convulsive e focal motor seizures with unconsciousness and focal motor seizure status. The treatment resulted in complete cessation of the attacks.It has been reported that bromide is effective for generalized tonic-clonic seizures and not for complex partial seizures, such as convulsive focal motor Seizures with unconsciousness, However our experiences providence that bromide is one of the useful therapeutic agents for intractable symptomatic localization-related epilepsy. (C) 2002 Elsevier Science B.V. All rights reserved.

The effects of nitrooxy alkyl apovincaminate VA-045 ((+)-eburunamenine-14-carboxylic acid(2-nitroxy-ethyl ester), VA) were investigated in acutely dissociated rat neocortical neurons by using a nystatin-perforated patch recording configuration. VA activated a steady-state outward current in a concentration-dependent manner, with an EC50 of 0.65 μM. The reversal potential for the current shifted 56.5 mV with tenfold changes in the extracellular K+ concentration, suggesting that the current was carried by K+. The VA-induced current was not suppressed by apamin (1 μM), charybdotoxin (1 μ M), Cs + (3 μM), Ba2+ (3 μM), 4-aminopyridine (10 μM) or glibenclamide (10 μM), whereas tetraethylammonium suppressed the current with an IC50 of 1.4 μM. These pharmacological properties of the VA-induced current were compatible with a slowly inactivating delayed rectifier current (Ik). It was suggested that the current activated by VA was Ik. The VA-induced current was not affected by Ca2+ depletion or by staurosporine (0.1 μM), quinacrine (10 μM), wortmanin (1 μM) or genistein (1 μM). The intracellular perfusion of GDPβS (0.4 μM) also had no significant effect. Thus, VA may directly activate the K+ channels.

To clarify the pathophysiology of tonic spasms, 21 patients with West syndrome were analyzed using ictal and interictal single photon emission computed tomography (SPECT). We focused on whether ictal perfusion changes were observed in the focal cortical region. Eight of the patients studied showed definite focal cortical ictal hyperperfusion, indicating that there is a unique subset of West syndrome that can be classified as infantile localization-related epilepsy. Of those eight patients, only two showed asymmetric spasms, suggesting that seizure symptomatology in infants gives only limited information on the localization-related nature of epilepsy. Furthermore, the activation of subcortical structures by focal cortical regions might be attributable to the symmetric seizure phenomena. Thirteen patients showed a diffuse pattern in their ictal SPECTs; this probably included patients with diffuse hyperperfusion and those with no changes. The following have yet to be determined: (1) whether West syndrome is divided into subgroups based on the origin of spasms, in that some patients have the origin in the cortical hemisphere and some have the origin in structures other than the cortical hemisphere, such as the brain stem; (2) whether differences in ictal SPECT patterns reflect a unique nature of tonic spasms in West syndrome, where tonic spasms appear in clusters and the interval of each spasm is different among each patient.

Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is the widespread accumulation of Rosenthal fibers. The most common form affects infants and young children, and is characterized by progressive failure of central myelination, usually leading to death before adulthood. Definitive diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the presence of Rosenthal fibers. However, missense mutations in the coding region of the glial fibrillary acidic protein (GFAP) gene have recently been associated with a high percentage of pathologically proven cases. Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A α-helix domain of GFAP. The nucleotide change was not found in 65 normal individuals (130 alleles). These results provide further support for a causative role for GFAP mutations in Alexander disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.

Two children with influenza A-related encephalopathy were treated with a combination of mild hypothermia (deep body temperature of the forehead: 35 degrees C) and anticytokine agents (high-dose methylprednisolone and ulinastatin), while receiving amantadine. One of the cases exhibited acute necrotizing encephalopathy on computed tomography (CT). Although no severe complications occurred, correctable hypokalemia and hyperglycemia occurred in both cases. Both patients recovered without any neurological sequelae. Our therapeutic protocol appears to be effective for managing influenza A-related encephalopathy.

We used interictal single photon emission computed tomography (SPECT) on 40 patients with West syndrome to determine whether cortical perfusion abnormalities are closely related to the development of West syndrome and whether they are correlated with the long-term seizure prognosis or the developmental outcome. Localized cortical perfusion abnormalities were seen in 24 patients (60%), while 15 patients (38%) were classified as normal. The remaining patient showed hyperperfusion of the basal ganglia bilaterally. Of 24 patients with localized perfusion abnormalities, unifocal cortical hypoperfusion was present in 11, multifocal hypoperfusion in 10, multiple cortical hypo- and hyperperfusion in one, hyperperfusion of the bilateral frontal cortices and brain stem in one, and focal hyperperfusion in the residual frontal cortex in one. For statistical analysis, we focused on 26 patients (cryptogenic; 10, symptomatic; 16), who were followed for more than 2 years after the onset of tonic spasms (mean 5.0 years). The results showed that focal cortical perfusion abnormalities were not correlated with the long-term seizure prognosis, the developmental outcome, or the response to ACTH therapy. In agreement with previous reports, the results of interictal SPECT suggested that focal cortical lesions play an important role in the development of West syndrome. However, statistical analysis showed that the existence of cortical dysfunction as defined by SPECT did not predict the seizure prognosis or the developmental outcome.

We report on a 3-year-old girl with West syndrome and with focal hypsarrhythmia. The left hemisphere of the patient was virtually completely defective and continuous hypsarrhythmia was only seen in the residual right frontal cortex, where an interictal single photon emission computed tomography (SPECT) showed hyperperfusion. Despite a focal epileptic pattern, the tonic spasms were quite symmetrical. In our patient, spasms might not require the sensorimotor cortex, but the brainstem containing the descending pathways that control spinal reflexes and other infratentorial structures seem to be essential for the occurrence of spasms. This is in accordance with the result of an ictal SPECT that showed hyperperfusion of the brainstem and cerebellum. These findings suggest that hypsarrhythmia originates from cortical lesions, while subcortical structures may be primarily responsible for the tonic spasms in this patient.

To examine sympathetic and vagal cardiovascular regulatory mechanisms in the pathogenesis of orthostatic hypotension in pheochromocytoma, we continuously monitored blood pressure (Finapres) and RR interval (electrocardiogram) in supine and standing positions in 12 patients with pheochromocytoma, 43 patients with essential hypertension, and 30 normotensive subjects. Mayer wave power spectrum of systolic blood pressure variability (approximate to 0.1 Hz) and respiratory power spectrum of the RR interval variability (approximate to 0.25 Hz) were taken as measures of sympathetic vascular and cardiac vagal modulations, respectively Systolic blood pressure decreased more upon standing in pheochromocytoma patients (-21 +/- 7 mm Hg) than in normotensive subjects (-5 +/- 2 mm Hg) or essential hypertensive patients (-3 +/- 2 mm Hg) (P < .005 for both), whereas heart rate tended to increase most in the pheochromocytoma group. Postural reduction in systolic blood pressure was highly correlated-with postural increase in heart rate (reciprocal change in RR interval) in the pheochromocytoma group (r = 0.716, P < .01) suggesting that baroreflex is well functioning in those patients. The Mayer wave power spectrum in recumbency was extremely depressed in pheochromocytoma patients (1.1 +/- 0.2 mm Hg-2) compared with normotensives (4.5 +/- 0.8 mm Hg-2) or essential hypertensives (5.6 +/- 0.6 mm Hg-2) (P < .001 for both). This parameter increased. significantly with standing in all groups but remained lower in patients with pheochromocytoma (5.1 +/- 1.0 mm Hg-2) than in normotensives (7.1 +/- 0.9 mm Hg-2, P = NS), whereas essential hypertensive patients demonstrated far greater value (19.2 +/- 3.8, P < .01 for both). The respiratory power spectrum of the RR interval in recumbency of pheochromocytoma patients (189 +/- 54 msec(2)) was less than in normotensive subjects (714 +/- 100 msec(2), P < .001) but did not differ from that in patients with essential hypertension (214 +/- 41 msec(2)). The respiratory power spectrum of the RR interval upon standing was markedly suppressed in pheochromocytoma patients (36.9 +/- 16.7 msec(2)) compared with normotensive subjects (129.5 +/- 23.6 msec(2)) or essential hypertensive patients (126.6 +/- 28.6 msec(2)) (P < .001 for both). Postural decrement in the respiratory power spectrum of the RR interval correlated positively with postural increase in heart rate (r = 0.577, P < .05) in patients with pheochromocytoma. After successful surgery (n = 9), the Mayer wave power spectrum of the systolic blood pressure and the blood pressure response to orthostasis were normalized. These data suggest that altered sympathetic vascular regulation is central to the pathogenesis of orthostatic hypotension in pheochromocytoma, whereas cardiac vagal regulation acts to compensate. (C) 1999 American Journal of Hypertension, Ltd.

We evaluated the ictal and interictal single photon emission computed tomography (SPECT) of 9 patients with West syndrome (WS). In this group, we noted two clear patterns of cortical hyperperfusion and subcortical hyperperfusion in the ictal SPECT. Both patterns were different from the previously documented ictal patterns for complex partial seizures (CPS) or secondarily generalized seizures. Our results suggest that the tonic spasms of WS do not always have a single neurophysiological basis; e.g., patients with hemihypsarrhythmia and focal hypsarrhythmia did not show ictal hyperperfusion of the lesion with hypsarrhythmia. These findings indicate that the origin of hypsarrhythmia as an EEG feature and the origin of tonic spasms may be different in such patients. In particular, hypsarrhythmia appears to originate from cortical lesions, whereas the subcortical structures may be primarily responsible for the tonic spasms. Our report is the first published study of ictal SPECT in patients with WS.