Evaluation of combination therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis.

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality, even with appropriate antiviral therapy. In the present investigation, the first to assess efficacy of corticosteroid treatment with aciclovir therapy in HSVE, multiple logistic regression analysis was performed of predictors of outcome in adult patients with HSVE. METHODS: A non-randomised retrospective study of 45 patients with HSVE treated with aciclovir was conducted. The patients were divided into poor and good groups based on outcome at three months after completion of aciclovir treatment. The variables evaluated were: clinical variables (sex, age, days after onset at initiation of aciclovir, Glasgow Coma Scale (GCS) at initiation of aciclovir, initial and maximum values for the cell numbers and protein concentration in the cerebrospinal fluid, and corticosteroid administration); neuroradiological variables (detection of lesions by initial cranial computed tomography and by initial magnetic resonance imaging); and one neurophysiological variable (detection of periodic lateralised epileptiform discharges on the initial electroencephalogram). Single variable logistic regression analysis was performed followed by multiple logistic regression analysis. The best set of predictors for the outcome of HSVE was estimated by stepwise logistic regression analysis. RESULTS: A poor outcome was evident with older age, lower GCS score at initiation of aciclovir, and no administration of corticosteroid. Patient age, GCS at initiation of aciclovir, and corticosteroid administration were found to be significant independent predictors of outcome on multiple logistic regression analysis, and these three variables also formed the best set of predictors (R(2) = 0.594, p<0.0001). CONCLUSION: Combination therapy using both aciclovir and corticosteroid represents one of the predictors of outcome in HSVE.

A continuing high incidence of subacute sclerosing panencephalitis (SSPE) in the Eastern Highlands of Papua New Guinea.

The aims of this descriptive study were to confirm the high incidence of subacute sclerosing panencephalitis (SSPE) previously reported from Papua New Guinea (PNG) and to relate SSPE to previous measles vaccination and measles illness. From February 1997 to April 1999 we diagnosed a total of 55 patients with SSPE at Goroka Base General Hospital in Eastern Highlands Province (EHP) of PNG. The diagnosis was based on high cerebrospinal fluid and serum measles virus antibody titres with progressive neurological disorder and myoclonic jerks. Of these 55 patients 42 were from EHP, including 32 whose onset was in the 2-year period 1997-1998. The annual incidence of SSPE in EHP in these 2 years was 98 per million population under 20 years of age, the highest ever reported. This incidence was more than ten times higher than the highest incidence in the prevaccine era reported from elsewhere. The mean age of onset of SSPE was 7.7 years (range 2.8-14.8 years) and the interval between measles and the onset of SSPE, where known, had a mean of 5.9 years and a range of 2.5-11.1 years. Among the SSPE patients 19 had a documented history of measles vaccination. Eight of these 19 also had documentation of previous measles illness; of these, seven were vaccinated after the development of measles and one was vaccinated 20 days before measles illness. Two non-SSPE children received vaccination twice which was documented and subsequently developed measles which was also substantiated by documentation. Two patients with SSPE yielded amplified nucleotide sequences of measles virus that were different from any of the vaccine strains. We found no evidence to implicate measles vaccination in the development of SSPE.

Correlations between P300 components and regional cerebral blood flows.

To evaluate the diagnostic importance of event-related potential P300, the correlation between P300 and regional cerebral blood flow (rCBF) was investigated in various brain regions in patients with multiple cerebral infarction (16 cases), chronic alcoholism (11 cases) and Alzheimer's disease (5 cases) and in seven healthy people. Cognitive function was also evaluated by mini-mental state examination. P300 latency and rCBF was measured by recording of evoked potentials using an oddball paradigm and stable xenon computed tomographic scanning, respectively. A significant (P<0.05) negative correlation between P300 and rCBF was observed in the thalamus in patients with multiple cerebral infarction and chronic alcoholism. In addition, a significant (P<0.01) negative correlation between P300 latency and the mini-mental state examination score and positive correlation between rCBF in the thalamus and the mini-mental state examination score were observed. These findings suggest that P300 latency is associated with rCBF in the thalamus and cognitive function.

Nationwide survey of the annual prevalence of viral and other neurological infections in Japanese inpatients.

OBJECTIVE: To estimate the annual prevalence of viral and other neurological infections at large hospitals in Japan during the period from 1989 to 1991. METHODS: A nationwide questionnaire survey on the numbers of inpatients with viral and other neurological infections was sent for completion to the chiefs of Departments of Internal Medicine, Neurology and Pediatrics at all hospitals with more than 200 beds. RESULTS: The average annual number of inpatients (and the number per 10(6) population) with encephalitis in large hospitals was estimated to be 2,200+/-400 (17.7+/-3.2), while it was 32,000+/-16,000 (258+/-129) for meningitis, and 650+/-50 (5.2+/-0.4) for myelitis. Among the inpatients with encephalitis, meningitis, and myelitis, an unknown etiology was the most common (51.2% in encephalitis, 73.2% in meningitis, and 36.3% in myelitis), followed by a viral etiology for all three diseases. CONCLUSION: The first estimate was made of the annual prevalence of viral and other neurological infections and their etiology in Japan.

'Iatrogenic' Wernicke's encephalopathy in Japan.

'Iatrogenic' Wernicke's encephalopathy has appeared to occur more frequently in Japan, probably induced by the change of our Japanese national health insurance policy in 1992. We report 4 nonalcoholic patients with such Wernicke's encephalopathy, which occurred during the early postoperative oral food intake period following intravenous nutrition without vitamin supplements. We analyzed the medical records of 4 patients, 3 men and 1 woman, aged between 55 and 71 years, who were admitted to our hospital between 1992 and 1995. Three patients underwent gastrointestinal surgery and 1 suffered chronic pyothorax. We diagnosed our patients as having Wernicke's encephalopathy based on typical neurological abnormalities, in addition to typical cranial magnetic resonance image findings, low serum vitamin B(1) levels, or both. Although all of the patients were treated with vitamin B(1) and showed some improvement, 1 patient developed Korsakoff syndrome, 2 made incomplete neurological recovery, and 1 died. We speculated that the body vitamin B(1) stores had been decreasing in our patients who did not receive any vitamin supplements during intravenous hyperalimentation or hydration. Subsequent administration of high calorie and high carbohydrate oral diets increased the demand for vitamin B(1), further depleting the vitamin stores, thereby causing 'iatrogenic' Wernicke's encephalopathy. The change of our national health insurance policy in 1992 discouraged the routine administration of vitamins, probably causing Wernicke's encephalopathy in our patients.

[A case of multiple cranial neuropathy with positive antinuclear antibody responded to steroid].

A 56-year-old woman was admitted to our hospital because of bilateral ptosis, total ophthalmoplegia, bilateral facial palsy and left hypoglossal nerve palsy. Antinuclear antibody (ANA) showed high titer of 1280 but other data were normal. With oral prednisolone therapy (40 mg/day), the symptoms improved gradually but ANA titer did not show any significant change. We thought multiple cranial neuropathy of the patient was due to autoimmune disease such as collagen disease or cranial nerve type of Guillain-Barré syndrome from her symptoms and positive ANA. In contrast to other reported cases of multiple cranial neuropathy with positive ANA, in our patient ANA titer was high, only motor cranial nerves were impaired, and total ophthalmoplegia was found. Steroid therapy was useful in accordance with other reports. Although our patient has no symptoms related to collagen diseases, a long follow-up of this patient is considered to be necessary.

Effects of bunazosin hydrochloride sustained-release formulation on cerebral circulation.

BACKGROUND: We investigated the cerebral blood flow in mild to moderately hypertensive patients with chronic cerebral infarction before and after the administration of bunazosin hydrochloride sustained-release formulation, a selective sympathetic alpha1 receptor blocker. METHODS: Eleven mild to moderately hypertensive patients (mean age 65.6 years) with chronic cerebral infarction were studied. INTERVENTIONS: The patients were on enalapril maleate, an angiotensin converting enzyme inhibitor, for one week and then enalapril maleate was switched to bunazosin hydrochloride sustained-release formulation. MEASURES: The cerebral blood flow study was performed before and 8 weeks after starting the administration of bunazosin hydrochloride sustained-release formulation. Cerebral blood flow was measured using the stable xenon CT method. The picture analysis was performed using AZ-7000. The regional cerebral blood flow was measured by placing the region of interest on the CT images. The regional cerebral blood flows were measured before and 20 minutes after intravenous injection of 17 mg/kg acetazolamide. RESULTS: The blood flows in the parietal cortex and caudate nucleus 8 weeks after starting the administration of bunazosin hydrochloride sustained-release formulation were significantly greater than those before. The cerebrovascular acetazolamide reactivity in the occipital cortex and caudate nucleus was significantly lower after switching to bunazosin hydrochloride sustained-release formulation than before. CONCLUSIONS: Considering the reports that angiotensin converting enzyme inhibitors show little influence on cerebral blood flow, the present study suggests that bunazosin hydrochloride sustained-release formulation may show a good influence on cerebral blood flow in mild to moderately hypertensive patients with chronic cerebral infarction.

Functional role of cyclin A on induction of fibroblast apoptosis due to ligation of CD44 matrix receptor by anti-CD44 antibody.

Ligation of cell surface matrix adhesion receptors such as integrins can increase expression of specific cell cycle regulatory proteins such as cyclin A, thereby regulating cell cycle progression. Disruption of cell surface matrix receptor interaction with the extracellular matrix can trigger apoptosis. Induction of apoptosis has been linked to unscheduled up-regulation of cyclin A and activation of cyclin-A-associated dependent kinase 2 activity due to cleavage of cyclin-dependent kinase inhibitors by caspases. We have found that ligation of the cell surface matrix adhesion receptor CD44 by anti-CD44 antibody induces cell detachment and triggers apoptosis. In this report we show that ligation of CD44 by anti-CD44 antibody increases the expression of cyclin A protein prior to activation of caspase-3-like activity and morphological changes of apoptosis. Down-regulation of cyclin A protein levels by cyclin A antisense oligonucleotides dramatically decreased fibroblast apoptosis in response to anti-CD44 antibody. These data identify an important functional role of cyclin A in the induction of fibroblast apoptosis due to the ligation of the cell surface adhesion receptor CD44 by anti-CD44 antibody.

Comparative study between chemiluminescence assay and two different sensitive polymerase chain reactions on the diagnosis of serial herpes simplex virus encephalitis.

OBJECTIVE: A prospective study was undertaken on the diagnosis of herpes simplex encephalitis (HSVE) by comparing chemiluminescence assay (CL) and two different sensitive polymerase chain reactions (PCRs). METHODS: The materials comprised 53 serial CSF samples from 31 patients with acute encephalitis with suspected HSVE. Each CSF was distributed to three independent laboratories to perform quantitative measurements by CL, the low sensitive (single) PCR, and high sensitive (nested) PCR. The CL provided a method of detecting HSV itself and the small fragment with HSV antigenicity which was composed of viral component proteins. The serial CSFs were found retrospectively to comprise 24 samples from 11 patients with HSVE due to HSV1 and 29 samples from 20 patients with non-HSVE. RESULTS: the CL showed 50 to 48 000 pfu/ml in all samples of HSVE (except one) taken from the 3rd to the 25th day. The low sensitive PCR demonstrated 50 to 47 000 pfu/ml in only six samples of HSVE. The high sensitive PCR disclosed less than 100 to 120 000 copies/ml in 11 samples of HSVE. At the acute stage from the 1st to 7th day, the sensitivities of CL and the high sensitive PCR were 100%, but that of the low sensitive PCR was 75%. The sensitivity of CL was significantly higher than those of both PCRs after the acute stage on the 15th to 32nd day. The specificities and positive predictive values of the three methods were 100%. However, the negative predictive value of CL was significantly higher than that of the low sensitive PCR. CONCLUSIONS: The sensitivity of CL is equivalent to that of the high sensitive PCR during the acute stage and significantly higher than that of the high sensitive PCR after the acute stage. A clear difference in sensitivity exists between the different PCRs. A combination of the PCR, chemiluminescence assay, and serological antibody diagnosis is currently considered the most effective approach for the clinical diagnosis of HSVE.

[A case of post-infectious wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome].

The patient is a 72-year-old man who had tonsillitis and underwent incision on March 6, 1998. He complained headache and nausea from March 10 and double vision from March 12. He was admitted to our hospital on March 14. Neurological examination on March 18 revealed bilateral internuclear ophthalmoplegia with exotropia (WEBINO), bilateral ptosis and disturbance of convergence. Lumbar puncture revealed moderately elevated protein (46 mg/dl) with normal pressure and cells. The T2-weighted images of head MRI showed multiple high intensity lesions in anterior commissure and right pons. After he was treated with methylprednisolone, his headache and ptosis disappeared. The lesion in anterior commissure on MRI disappeared also. But WEBINO remained at the time of discharge. WEBINO syndrome is caused by lesion of pons and midbrain. The most common cause of bilateral internuclear ophthalmoplegia is multiple sclerosis in the European and American countries, but the frequency of vascular origin is higher in Japan than in the European and American countries. All the cases of WEBINO syndrome reported in Japan are vascular origin. This is the first case of WEBINO syndrome not of vascular origin.

Blinded, prospective, and serial evaluation by quantitative-EEG in interferon-alpha-treated hepatitis-C.

OBJECTIVES: To estimate the effect of brain function due to IFN-alpha in chronic hepatitis C patients by the quantitative EEG. METHODS: 56 chronic hepatitis C patients were administered IFN-alpha intramuscularly at 9x10(6) IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained in each subject before, at 2 and 4 weeks, and after completing the treatment. Resting EEG without artifacts was selected for quantitative EEG analysis, which was performed blindly. The frequency range was divided into delta to beta. The absolute and relative powers of each frequency band in each subject were calculated and the differences of these powers at different stages were analyzed statistically. RESULTS: The absolute powers of slow waves (delta, theta 1, and theta 2) increased while alpha 2 and fast wave (beta) decreased significantly at all locations during IFN-alpha administration. The total power and alpha 1 values revealed no significant alterations. The relative power revealed the same alteration during treatment. These changes disappeared following the treatment. Such diffuse slowing in the EEG was revealed by the total change in the whole subjects. CONCLUSIONS: Diffuse slowing in the EEG was induced by IFN-alpha, was reversible, and was evident as the total change in the subjects. These findings suggested mild IFN-alpha-induced encephalopathy.

Central and peripheral motor conduction time in chronic alcoholics with polyneuropathy and/or spasticity.

We measured central and peripheral motor conduction time to demonstrate lesions in the upper and lower motor neurons of 11 chronic alcoholics with polyneuropathy without spasticity, 7 chronic alcoholics with spasticity with and without alcoholic polyneuropathy, and 16 healthy volunteers as controls. Peripheral motor conduction time was significantly prolonged in all extremities in all of the chronic alcoholics, and was accompanied by a considerable reduction in motor conduction velocity. Central motor conduction time was considerably prolonged in the lower extremities of the alcoholics with spasticity compared with both the controls and the alcoholics without spasticity. Central motor conduction time in the patients with alcoholic polyneuropathy without spasticity was slightly prolonged in comparison with the controls, but not significantly. Based on the electrophysiological findings, we conclude that peripheral neuropathy is a lesion common to chronic alcoholics whether or not they have clinically evident polyneuropathy. Chronic alcoholics with spasticity have significantly longer central motor conduction time in the lower extremities. Spasticity in chronic alcoholics develops not independently but concomitantly with peripheral neuropathy, suggesting that peripheral neuropathy develops earlier than spasticity.

[The clinical features of cervical spondylosis with boule musculaire].

To clarify the pathophysiology of boule musculaire associated with cervical spondylosis, we investigated the 13 patients (11 males and 2 females) with cervical radiculopathy caused by cervical spondylosis. None of the patients had any subjective symptoms such as sensory disturbance, weakness in the boule musculaire, and muscle atrophy of the insurround region near the boule musculaire. Among 21 tendon reflexes of the biceps muscle of the arm, 9 were normal, 8 were decreased and 4 were increased. Among the 13 patients there was only 2 clinical cases of cervical myelopathy. MRI obtained from 3 patients demonstrated a compressed cervical cord. Electromyography obtained from 7 patients demonstrated mild neurogenic changes such as polyphasic or prolonged motor unit potential (MUP) in the boule musculaire and in the atrophic regions. However, there was no giant MUP, fasciculation, fibrillation, nor positive sharp waves suggesting denervating lesions below the anterior horn in any patient. It was considered that the boule musculaire observed in cervical spondylosis gradually developed from a relatively mild disturbance of the ventral root. Moreover, the boule musculaire developed more often in the male patients, and predominantly on the right side. Cervical spondylosis accompanying boule musculaire may be a prodromal stage or a mild type of cervical spondylotic amyotrophy.

Central motor conduction time in Parkinson's disease.

Central motor conduction time (CMCT) was analysed in 11 patients with Parkinson's disease and 10 age matched healthy controls. CMCT was measured during muscle relaxation, muscle contraction and in patients with Parkinson's disease before and 1 h after intravenous infusion of L-dopa (0.25%, 20 ml). Although the CMCT during muscle contraction did not differ significantly between Parkinson's disease and healthy controls, the CMCT during muscle relaxation was significantly shorter in Parkinson's disease than in healthy controls. The CMCT during muscle relaxation in Parkinson's disease was significantly longer after intravenous infusion of L-dopa than before, but the CMCT during muscle contraction did not differ significantly before and after intravenous infusion of L-dopa. The CMCT during muscle contraction was significantly shorter than the CMCT during muscle relaxation in healthy controls. However, in Parkinson's disease, the CMCT did not differ significantly between muscle relaxation and contraction. We consider that the central motor conduction pathway during muscle relaxation in Parkinson's disease is modified to be similar to that during muscle contraction in healthy subjects. Copyright 1999 Harcourt Publishers Ltd.

Regional differences in cerebrovascular reactivity to acetazolamide in Alzheimer's disease.

The cerebral blood flow and cerebrovascular reactivity to acetazolamide were investigated in Alzheimer's disease using stable xenon computed tomography (CT). Ten patients with Alzheimer's disease and 10 healthy controls were studied. The regional cerebral blood flow was measured using the xenon delivery and analysis system (AZ-7000 model, Anzai Sogyo, Tokyo, Japan) and CT (PreSage, Yokogawa Medical Systems, Tokyo, Japan). The subjects inhaled room air followed by a mixture of 30% xenon and 50% oxygen for 3 min. Serial scanning was performed once before xenon inhalation, three times in the wash-in process and five times in the washout process of 5 min. The xenon concentration in the end-tidal expired gas was recorded continuously by the thermoconductivity method. The regional cerebral blood flow was measured before and 20 min after i.v. injection of 17 mg/kg acetazolamide. The blood flows in the frontal lobe, parietal lobe and temporal lobe were reduced but the blood flows in the caudate nucleus, putamen and thalamus were normal in the Alzheimer's disease group. The cerebrovascular reactivity to acetazolamide was reduced in the frontal, parietal and temporal cortex but was normal in the other areas. There is a regional difference in the cerebral blood flow and the cerebrovascular reactivity to acetazolamide in Alzheimer's disease Copyright 1999 Harcourt Publishers Ltd.

Simultaneous measurement of velocity and length of moving surfaces by a speckle velocimeter with two self-mixing laser diodes.

A novel laser speckle velocimeter with two self-mixing laser diodes (SM-LD's) for velocity and length measurements of moving surfaces is reported. The mean frequency of the speckle signal obtained in the measurement system depends on the surface path illuminated by the SM-LD. This behavior of the speckle signal in the SM-LD's is exploited to detect the front and the end edges of a target surface by sampling continuously the number of intensity changes in a speckle signal waveform. Once the edges are determined, the velocity and the length of the surface are calculated easily. The error for length and velocity measurements of a target with a homogeneous rough plane surface of 60-mm length, moving at a velocity of 200 mm/s, can be as low as 2.1% and 1.75%, respectively.

Magnetic stimulation in cervical radiculopathy and health controls.

Magnetic stimulation was performed in 15 cases of unilateral cervical radiculopathy and 16 age-matched healthy controls. Among the muscle potentials which have acute slope and high amplitude, the difference between the minimal and the maximal latency in the same muscle was defined as variability. In the healthy control group, the variability of the muscle potentials evoked by head magnetic stimulation was approximately 2 ms. In cervical radiculopathy, the muscle potential latencies in head magnetic stimulation were normal except for one case because of the wide normal range. However, the interside difference of the muscle potential latency in head magnetic stimulation was significantly greater in the cervical radiculopathy group than in the healthy control group. This suggests that the interside difference of the muscle potential latency is more sensitive than the muscle potential latency in head magnetic stimulation in unilateral radiculopathy.

Central motor conduction time and regional cerebral blood flow in patients with leuko-araiosis.

Central motor conduction time (CMCT) and regional cerebral blood flow were investigated in 21 patients with leuko-araiosis. The severity of dementia was examined using mini-mental state examination. The head magnetic stimulation was performed using an SMN-1100 magnetic stimulator and a round coil with a diameter of 17 cm. The regional cerebral blood flow was measured using the stable xenon computed tomography method. The CMCT was significantly longer in the patients with dementia than in the patients without dementia. The blood flows in the parietal cortex, frontal white matter and thalamus were significantly lower in the patients with dementia than in the patients without dementia. There were significant negative correlations between the CMCT and the blood flows in the frontal cortex, temporal cortex, frontal white matter and thalamus. The significant negative correlations suggest that the prolongation of CMCT in patients with leuko-araiosis is related to the decrease in regional cerebral blood flows.

Improvement of P300 latency by treatment in non-insulin-dependent diabetes mellitus.

P300 event-related potentials were investigated in 24 cases of non-insulin-dependent (Type II) diabetes mellitus (NIDDM) without apparent central nervous system (CNS) symptoms and without cerebrovascular diseases on head magnetic resonance imaging, and in 16 age-matched healthy control subjects. N200 and P300 latencies were significantly prolonged and N200 and P300 amplitudes were significantly smaller in the NIDDM group than in the healthy control group. P300 latency was significantly shorter after the treatment than before. N200 and P300 waves have been recognized as useful indicators of cognitive function. The present study suggests that cognitive function is impaired in NIDDM patients and may improve with treatment of hyperglycemia.

Effectiveness of traditional Chinese medicine in Alzheimer disease.

Effects of traditional Chinese medicine on dementia, P300, cerebral blood flow, and cerebrospinal fluid (CSF) examination were investigated. Ten patients with Alzheimer disease (AD) who agreed to take traditional Chinese medicine were studied. The traditional Chinese medicine was given for 3 months and the Mini-Mental State Examination (MMSE), P300 examination, cerebral blood flow examination, and CSF examination were performed before and after taking the traditional Chinese medicine. The scores of the MMSE, the P300 latency, and blood flow in the cerebral cortex in AD improved with treatment with the traditional Chinese medicine. The concentration of alpha-aminobutyric acid in the CSF decreased with treatment with the traditional Chinese medicine. The improvement is considered to be not a placebo effect. Key Words: T