The effect of flunarizine on essential tremor.

We investigated the effect of flunarizine treatment (10 mg/d) in 17 subjects with essential tremor in a double-blind placebo-controlled design. Tremor was assessed by clinical scoring, tremographic recordings, and subjective rating by subjects. Of the 15 subjects who completed the study, 13 showed improvement. We conclude that flunarizine is effective treatment for essential tremor.

Choroido-cerebral calcification syndrome with retardation.

We present a sibship with a rare syndrome characterized by mental retardation, dense calcification of the lateral ventricular choroid plexus, and increased CSF protein. Neurophysiologic studies yielded nonspecific results, and endocrine studies, including parathormone levels, were normal. Simultaneous measurements of CSF and serum calcium, magnesium, and other electrolytes were normal, but the CSF/serum ratio of phosphate was low, suggesting a possible role in the pathogenesis of this syndrome.

Neurobrucellosis: clinical characteristics, diagnosis, and outcome.

We report 13 patients with neurobrucellosis categorized into five groups: acute meningoencephalitis; papilledema and increased intracranial pressure, meningovascular, CNS demyelinization, and peripheral neuropathy. We treated the patients successfully, without relapse, with two or more antimicrobials: rifampicin, co-trimoxazole, and doxycycline.

The effect of nimodipine on essential tremor.

We investigated the effect of nimodipine (30 mg qid) in 16 de novo patients with essential tremor in a double-blind placebo-controlled study in which we assessed tremor by clinical scorings, tremorgraphic recordings, and patient self-evaluation. Of the 15 patients who completed the study, eight improved. We conclude that nimodipine is effective in some patients with essential tremor.

Neurological recovery in diabetic rats following spinal cord injury.

This study was designed to assess the effect of spinal cord injury on neurobehavioral, electrophysiological, structural, and biochemical changes in normal and diabetic rats. Experimental diabetes was induced in Sprague-Dawley male rats (weighing 250-280 g) with streptozotocin (50 mg/kg i.p.). Eight weeks after the treatment with streptozotocin the animals were anaesthetized with chloral hydrate and laminectomy was performed at T 7-8 level leaving the dura intact. A compression plate (2.2 x 5.0 mm) loaded with a weight of 35 g was placed on the exposed spinal cord for 5 min. Postoperative neurological function was assessed using inclined plane test, modified Tarlov score, and vocal and sensory score daily for 10 days. Electrophysiological changes were assessed using somatosensory and corticomotor evoked-potentials. The animals were sacrificed at different time intervals and injured site of the spinal cord was analyzed for changes in vitamin E and glutathione levels (as markers of oxidative stress). Pathological changes in spinal cord were also studied using light microscopy. The data on neurobehavioral study clearly indicated that the compression of spinal cord produced highly significant neurological deficit and poor recovery in diabetic rats as compared to nondiabetic rats. Our histopathological and electrophysiological results also confirmed that diabetic animals are more susceptible to compressive spinal cord injury as compared to nondiabetic animals. A higher depletion of antioxidant defense markers (vitamin E and glutathione) was observed in diabetic rats as compared to nondiabetic rats. These results point toward the role of free radicals in poor recovery in diabetic rats following neurotrauma. Further studies are warranted to assess the neuroprotective potential of antioxidants to retard the secondary pathophysiological events following neurotrauma and to enhance the recovery.

Diethyldithiocarbamate (DEDC) impairs neuronal recovery following sciatic nerve injury in rats.

PURPOSE: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC has received considerable attention because of its clinical applications and potential role in mediating both the toxic and therapeutic actions of disulfiram which is frequently used for alcohol aversion therapy. DEDC is known for its multiplicity of action that exerts both pro- and antioxidant effects. In rodents DEDC has been shown to produce neuroprotective as well as neurotoxic effects. The purpose of this study was to examine the effect of DEDC on neurological recovery following sciatic nerve crush injury (SNCI) in rats. METHODS: Adult female Wistar rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and then once daily for 60 days. The animals were observed for sciatic functional index (walking deficit), electrophysiological and histological changes. Vitamin E level was measured to deter-mine antioxidant status of sciatic nerve. RESULTS: Crush injury to the sciatic nerve resulted in a significant impairment of functional response which gradually recovered over a period of 22 days. Treatment of animals with DEDC caused a significant delay in functional recovery which was accompanied by poor histo-logical and electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a significant decrease in vitamin E levels in both injured and uninjured sciatic nerves. CONCLUSIONS: Our results demonstrate that exposure to DEDC adversely affects recovery from peripheral nerve injury. The delay may to some extent be attributed to DEDC induced oxidative stress.

Guillain-Barre syndrome: a series observed at Riyadh Armed Forces Hospital January 1984--January 1994.

A consecutive series of 47 hospitalized cases of Guillain-Barre syndrome seen over a 10-year period was analysed with respect to: (1) age and sex; (2) antecedent events and seasonal distribution; (3) patterns of clinical presentation; (4) CSF and neurophysiological findings; (5) results of treatment with plasma exchange; and (6) outcome. Twenty-two were children, 20 middle-aged and 5 aged; 37 were male and 10 were female. The most frequent antecedent event was upper respiratory tract infections; a seasonal peak incidence was found in winter. Clinical, CSF and neurophysiological findings concurred with those in the Western literature; 79% of the cases were severe. Plasma exchange performed within the first 2 weeks of onset benefitted in the short-term outcome, i.e. improvement by 1 grade at 4 weeks, but the long-term benefit, i.e. the ability to regain independent locomotion, was questionable. Plasma exchange helped in curtailing the time to walking unaided but had no benefit on the duration of artificial ventilation. Factors associated with an adverse outcome were: age over 15 years, severity of motor electrodiagnostic findings (especially a decreased distal CMAP amplitude and EMG signs of acute denervation), requirement for ventilation and slow progression (>3 weeks) to maximum deficit. After a mean follow-up of 11 months, 55% of the patients regained independent locomotion, which is a comparatively low proportion.

Vitamin E decreases valproic acid induced neural tube defects in mice.

The present study was undertaken to investigate the effect of vitamin E on valproic acid (VPA) induced teratogenesis. Pregnant Balb mice were divided into six groups of 10-11 animals each. The mice in group 1 served as control and were injected with saline subcutaneously on day 8 of gestation, whereas, animals in group 2 received a single injection of VPA (700 mg/kg (s.c.)). Groups 3 and 4 received an oral administration of vitamin E in the doses of 250 and 500 mg/kg, respectively, 1 h before VPA injection. Group 5 and 6 were given vitamin E only, in the same doses as group 3 and 4. On day 18 of gestation, the mice were killed by cervical dislocation. Embryotoxicity was assessed by counting the number of implants, live and dead fetuses, resorptions, crown rump length and fetal body weight. The fetuses were observed for malformations including neural tube defects (excencephaly), open eye lid and micrognathae. VPA administration resulted in a significant reduction of the average live fetuses/litter, fetal weight and crown rump length and a significant increase in malformations (excencephaly, open eye lid and micrognathae). Concomitant administration of vitamin E significantly attenuated VPA induced decrease in the fetal weight, crown rump length and malformations.

Nitric oxide synthase inhibitor aminoguanidine potentiates iminodipropionitrile-induced neurotoxicity in rats.

This investigation was undertaken to study the effect of nitric oxide synthase inhibitor, aminoguanidine on iminodipropionitrile (IDPN)-induced neurobehavioral and vestibular toxicity in rats. The dyskinetic syndrome was produced in male Wistar rats by i.p. injections of IDPN (100 mg/kg) for 6 days. Aminoguanidine was administered orally in the doses of 50, 150 and 300 mg/kg, 60 min before IDPN in three different groups. Control rats received vehicle only, whereas another group was treated with 300 mg/kg of aminoguanidine alone (without IDPN). Our results showed that aminoguanidine significantly and dose dependently exacerbated the incidence and intensity of IDPN-induced dyskinetic head movements. Aminoguanidine potentiated IDPN-induced loss of air righting reflex. The histopathological examination of inner ear showed aggravation of IDPN-induced degeneration of sensory hair cells in the crista ampullaris by aminoguanidine. These results suggest the role of nitric oxide in IDPN-induced neurobehavioral and vestibular toxicity.

Baclofen attenuates harmaline induced tremors in rats.

Recent experimental and clinical studies clearly suggest the role of gamma-aminobutyric acid (GABA) in the pathogenesis of tremors. The present study was undertaken to investigate the effect of baclofen, a GABA B receptor agonist on harmaline induced tremors. Four groups of female Wistar rats weighing 100+/-15 g were injected with harmaline (10 mg/kg, intraperitoneally) for inducing experimental tremors. The animals in groups 2, 3 and 4 were given baclofen by gavage at doses of 2.5, 5 and 10 mg/kg, respectively, half an hour before harmaline administration, whereas, the rats in group 1 served as control and received water. The latency of onset, intensity and duration of tremor and electromyographic (EMG) responses were recorded. Treatment with baclofen resulted in a dose dependent decrease in the intensity of tremor. Our EMG study also revealed a significant decrease in the amplitude of tremors in baclofen treated rats. A highly significant increase in latency of onset of tremor was observed in the rats treated with high dose (10 mg/kg) of baclofen only. This study clearly suggests beneficial effects of baclofen in harmaline induced tremors.

A new neurocutaneous syndrome possibly related to Ota's nevus.

The case of a 42-year-old Sudanese man is reported who had developed hyperpigmentation of the left face and rapidly progressive right hemiparesis followed by myoclonus at the age of 30. Blue-grey hyperpigmentation was noted in the territory of the left ophthalmic, maxillary and mandibular trigeminal nerve branches, with alopecia of the right face and axilla. CT of the brain revealed left-sided paraventricular calcifications and MRI showed atrophy of the left cerebral hemisphere and mesencephalon, a calcified haemangioma in the left basal ganglia, an old infarct in the right central pons, and cerebellar atrophy. This case resembles Ota's syndrome; however, atypical distribution of the facial nevus, the epidermal location of hyperpigmentation, and the combination of vascular and degenerative cerebral malformations indicate that this is a new hitherto unreported neurocutaneous vascular syndrome.

Heat strokes: aetiopathogenesis, neurological characteristics, treatment and outcome.

Heat stroke is a thermal insult to the cerebral thermoregulatory system controlling heat production and heat dissipation. The thermal insult may be environmental as in 'classic heat stroke' or endogenous as in 'exertional heat stroke' in joggers or runners. The insult will lead to a steady rise in body core temperature to 40 degrees C or more, exhaustion of sweating with hot dry skin and central nervous system disturbances ranging from confusion to deep coma. Multisystem insult will follow leading to a fatal outcome, if not diagnosed and treated promptly. Rapid evaporative cooling and support of vital organs are the essential factors in the management of this condition. If treated early, no sequelae results, however, pancerebellar syndrome and spastic or flaccid paraparesis have been described in a few cases. Limited sun exposure, proper use of sunscreens, adequate fluid and electrolyte replacement and acclimatization are the key factors for prevention. Despite appropriate prevention and prompt treatment, heat stroke is unlikely to be totally prevented, but the mortality has improved dramatically to less than 10%.

Intractable hiccup induced by brainstem lesion.

Four patients with brainstem lesions presented with intractable hiccup and mild to moderate neurological signs. Two of the patients had been initially diagnosed as having a psychogenic cause for their hiccup. Magnetic resonance imaging (MRI) demonstrated brainstem infarction in one case, tuberculoma at the junction of the medulla oblongata and the cervical spinal cord in two, and a vermian tuberculoma compressing the brainstem in one. The brainstem infarct and one of the medullary tuberculoma were not detected on high resolution enhanced computed tomography. The 3 patients with CNS tuberculoma were free of hiccup 1-5 months after antituberculous chemotherapy. It is proposed that hiccup is not an abnormal reflex, but a myoclonus generated by repetitive activity of the "inspiratory solitary nucleus" due to release of higher nervous system inhibitory/-regulatory control. The neuroanatomical network and the mechanisms underlying the formation of intractable hiccup are outlined. The value of MRI in the initial diagnosis and follow-up of patients with intractable hiccup due to brainstem lesions is emphasised.

Non-progressive familial congenital cerebellar hypoplasia.

A syndrome is reported of congenital non-progressive, gradually slightly improving, ataxia in 3 out of 5 male sibs, issues of a first-order consanguineous mating. Additional characteristic features included: moderate microcephaly, generalised muscle weakness and hypotonia, nystagmus, and moderate mental retardation. A pyramidal syndrome of hyperreflexia and Babinski signs, without any spasticity, became manifest in the 2nd or 3rd year of life. In all three, the caudal part of the vermis was absent, the enlarged IVth ventricle opening up via Magendie's foramen into the cisterna magna. The middle and rostral vermian parts as well as the sagittal paravermian parts of the cerebellar hemispheres were hypoplastic. The differential diagnosis of this syndrome is analysed and the developmental pathogenetic mechanisms likely to produce the typifying distribution of aplasia are indicated.

Bickerstaff brainstem encephalitis. A grave non-demyelinating disease with benign prognosis.

We describe 6 patients with ophthalmoplegia, ataxia and normal or exaggerated deep tendon reflexes. All had been preceded by a febrile illness and had a full recovery without sequelae. The brainstem auditory evoked potentials showed a localised lesion in the upper brainstem while the pattern shift visual evoked potentials were normal and did not show any additional silent lesions. CSF IgG oligoclonal bands were not detected in any of the patients. MRI in 2 patients showed a confluent high intensity lesion in the upper mesencephalon and thalamus involving white and gray matter. Follow-up ranged from 6 to 24 months and showed no relapse.

Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents.

Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30 mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30 and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two hours after the last injection of MPTP, striata were collected for the analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6-OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4 days, while first injection was given 30 min before 6-OHDA. On day 5, rats were sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6-OHDA significantly reduced striatal DA, which was significantly attenuated by QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA-induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2 in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA2 inhibitors for the treatment of Parkinson's disease.

Dipyridamole attenuates the development of iminodipropionitrile-induced dyskinetic abnormalities in rats.

The present investigation was undertaken to study the effect of dipyridamole on experimental dyskinesia in rats. The movement disorders were produced by intraperitoneal administration of iminodipropionitrile (IDPN) in the dose of 100 mg/kg per day for 12 days. Dipyridamole was administered orally, daily 30 min before IDPN in the doses of 0.5 g/kg, 1 g/kg, and 1.5 g/kg bodyweight in three different groups of rats. Twenty-four hours after the last dose of IDPN, animals were observed for neurobehavioral changes including vertical and horizontal head weaving, circling, backwalking, grip strength, and righting reflex. Immediately after behavioral studies brain specimens were collected for analysis of vitamin E, conjugated dienes, and lipid hydroperoxides as indices of oxygen-derived free radical (OFR) production. Our results showed that concurrent use of dipyridamole significantly protected rats against IDPN-induced neurobehavioral changes in a dose-dependent manner. Treatment of rats with dipyridamole inhibited IDPN-induced decrease of vitamin E and increase in conjugated dienes and lipid hydroperoxides in brain. These findings suggest the involvement of OFR in dipyridamole induced protection against the development of IDPN dyskinesia. Further studies are warranted to determine the role of dipyridamole as a prophylactic agent against the drug induced dyskinetic abnormalities.

Effect of aluminum on neurological recovery in rats following spinal cord injury.

OBJECT: This investigation was undertaken to study the effect of aluminum on neurobehavioral, electrophysiological, structural, and biochemical changes in rats following spinal cord injury (SCI). METHODS: Adult male Sprague-Dawley rats classified into different groups were given aluminum sulfate-dosed drinking water in the concentrations of 0%, 0.25%, 0.5% and 1%, respectively. After 30 days of aluminum treatment, the animals were subjected to spinal cord trauma. Laminectomy was performed at T7-8 in anesthetized rats, followed by placement of a compression plate (2.2 x 5 mm) loaded with a 35-g weight over the exposed spinal cord for 5 minutes. Control animals underwent the same surgical procedure, but the compression injury was not induced (sham). Postoperative neurological function was assessed using the inclined-plane test and by obtaining a modified Tarlov score and vocal/sensory score daily for 10 days. Electrophysiological changes were assessed using corticomotor evoked potentials, whereas pathological changes were assessed by light microscopy. The level of vitamin E in the spinal cord was measured as an index of antioxidant defense. The behavioral, biochemical, and histological analyses were performed in a blinded fashion. CONCLUSIONS: Analysis of results obtained in the behavioral studies revealed that the compression of spinal cord produced transient paraparesis in which a maximum motor deficit occurred at Day 1 following SCI and resolved over a period of 10 days. Administration of aluminum significantly impaired the recovery following SCI. Analysis of the results of the biochemical, electrophysiological, and histopathological studies also confirmed the deleterious effects of aluminum on recovery from SCI in rats.

Effect of lidocaine on harmaline-induced tremors in the rat.

The present study was undertaken to investigate the effect of lidocaine on harmaline-induced tremors in the rat. Four groups of Wistar rats weighing 45-50 g were injected with harmaline (50 mg/kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3, and 4 were also given lidocaine i.p. at doses of 12.5, 25, and 50 mg/kg, respectively, 10 min after the onset of tremors (therapeutic study). In a separate four groups of animals intraperitoneal lidocaine injection was given 10 min before harmaline (prophylactic study) in the same dose regimen as mentioned above. The latency of onset, intensity, and duration of tremor and electromyographic responses were recorded. Lidocaine dose dependently attenuated harmaline-induced tremors in rats. The latency period was increased, and duration and intensity of harmaline-induced tremors was reduced by lidocaine. Our electromyography (EMG) study also revealed a decrease in the amplitude of harmaline-induced tremors in lidocaine-treated rats. In conclusion, the results of this study clearly suggest beneficial effects of lidocaine in harmaline-induced tremors.

Exacerbation of iminodipropionitrile-induced behavioral toxicity, oxidative stress, and vestibular hair cell degeneration by gentamicin in rats.

This study describes the effect of gentamicin, an aminoglycoside antibiotic on iminodipropionitrile (IDPN)-induced abnormal neurobehavioral syndrome in female Sprague-Dawley rats. The animals were exposed to IDPN in the dose of 100 mg/kg/day intraperitoneally for 7 days. Gentamicin (GM) was administered intraperitoneally daily 1 h before IDPN in the doses of 10, 40, and 80 mg/kg body weight in three different groups of rats. One more group of animals received gentamicin alone (80 mg/kg) and served as the gentamicin-alone group. The intensity of IDPN induced characteristic excitation with choreiform, and the circling movement (ECC) syndrome was examined using an observational test battery including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of the righting reflex on days 6, 8, 10, 12, 19, 26, and 33. The animals for histopathological observation were sacrificed on day 10, whereas the remaining animals that were used for long-term behavioral studies were sacrificed on day 35 for biochemical observations. The blood and brain samples were collected for the analysis of blood urea nitrogen (BUN), serum creatinine, cerebral malondialdehyde (MDA), conjugated dienes, and lipid hydroperoxides, whereas temporal bones were collected for inner ear histopathology. Our results showed that gentamicin significantly and dose dependently exacerbated the incidence and the severity of the IDPN-induced behavioral syndrome. The histopathology of the inner ear demonstrated more severe loss of sensory hair cells in the crista ampullaris of the rats treated with IDPN plus gentamicin compared to the IDPN-alone treated animals. Concomitant treatment with gentamicin also potentiated IDPN-induced increase in free radical indices, suggesting a possible role of oxidative stress in gentamicin-induced aggravation of IDPN toxicity. Further studies are warranted to determine the role of aminoglycosides in nitrile toxicity and drug-induced movement disorders.