flunarizine and Cerebral-Infarction

Topics: Animals; Anticonvulsants; Brain; Calcium Channel Blockers; Cerebral Infarction; Disease Models, Animal; Fatty Acids, Nonesterified; Flunarizine; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Nimodipine; Piperazines; Verapamil

An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery.. The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other "stroke therapies" were not allowed. Patients were followed up for 24 weeks.. After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group.. Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Calcium Channel Blockers; Cerebral Infarction; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Flunarizine; Humans; Male; Middle Aged; Netherlands; Neurologic Examination; Scandinavian and Nordic Countries; Tomography, X-Ray Computed

We prospectively studied 26 patients with ischemic stroke within 24 hr, after 2 wk, and after 6 mo with thallium-201-diethyldithiocarbamate single-photon emission computed tomography (SPECT) and neurologic and functional assessments. The admission flow deficits correlated with outcome. The admission and 6-mo scores correlated with clinical conditions at each time. At 2 wk, the flow deficits were smaller and did not correlate with clinical parameters. Nor did the presence or absence of hyperfixation of the radiopharmaceutical. Six months after the infarct, the flow defect had decreased in 9 of 15 patients in whom three serial scans were available, with better clinical improvement than in the remaining six whose flow deficits increased. More patients in the first group had been treated randomly with the calcium-entry blocker flunarizine. SPECT imaging of rCBF within 24 hr after stroke correlates with clinical outcome and condition, whereas rCBF imaging at 2 wk after the stroke shows no clinical correlation.

Topics: Aged; Aged, 80 and over; Cerebral Infarction; Cerebrovascular Circulation; Ditiocarb; Double-Blind Method; Female; Flunarizine; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

We report a 27-year-old woman, a known case of classical migraine headache, on oral contraceptive pills. She had a severe episode of migraine with visual aura attack, which continued late into the night. The next early morning, her headache persisted and she developed abrupt onset of dysarthria, right hemiparaesthesias. She attributed symptoms to her long-standing headache problem, and hence did not seek medical help for the next two weeks. The symptoms persisted despite her headache subsiding over the next 24 hours. She worsened 2 weeks later during another such episode of headache. This time, she developed right hemiparesis. The patient was admitted with provisional diagnosis of stroke. MRI of the brain showed left temporoparietal lesion and was radiologically compatible with cortical laminar necrosis.Extensive work-up was done to rule out other causes of young stroke. The patient improved with antiplatelets, antimigraine prophylaxis and stroke rehabilitation therapy.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Aspirin; Cerebral Cortex; Cerebral Infarction; Diagnosis, Differential; Female; Flunarizine; Fructose; Humans; Magnetic Resonance Imaging; Migraine with Aura; Naproxen; Necrosis; Stroke Rehabilitation; Topiramate

Four patients presented symptoms of a dementia syndrome. A man aged 67 showed gradual aggravation of disorders of memory and gait, as well as subcortical infarctions. A man aged 65 had disorders of concentration non compatible with the infarctions on the MRI scan, which disappeared after discontinuation of use of flunarizine. A woman aged 55 and a man aged 52 had changes of character and infarctions in the frontal lobe. Vascular dementia is, contrary to what most criteria suggest, often a subcortical syndrome. The relationship between cerebrovascular pathology on CT and MRI scans and cognitive and behavioural disorders is often hard to establish. If the criteria for vascular dementia are applied blindly, other causes of the subcortical dementia syndrome can be missed. The present criteria offer almost no room for detecting the subtle cognitive and behavioural disorders of cerebrovascular pathology. It is important to recognize the early changes of a threatened brain, because treatment and prevention might be effective in preventing further damage.

Topics: Aged; Brain; Calcium Channel Blockers; Cerebral Infarction; Cognition Disorders; Dementia, Vascular; Depressive Disorder; Diagnosis, Differential; Fatal Outcome; Female; Flunarizine; Humans; Magnetic Resonance Imaging; Male; Mental Disorders; Middle Aged; Neurologic Examination; Neuropsychological Tests; Tomography, X-Ray Computed

We examined whether the anti-ischemic effect of lamotrigine (LTG), which inhibits the presynapic sodium channel, could be enhanced by the calcium channel blocker-flunarizine (FNR) in cerebral ischemia. Global ischemia was induced in Mongolian gerbils for 5 min under the monitoring of scalp temperature. LTG and FNR were administered intraperitoneally 1 h before ischemia. After 7 days, animals were killed and viable neurons in CA1 area were counted. LTG treated group showed significant protective effects compared to control group (P < 0.01). These effects were more prominent in group treated with LTG and FNR (P = 0.01). Combination of two drugs did not increase the mortality rate compared to single-treated group. These results show that a synergistic reduction of neuronal death can be achieved by combination of LTG and FNR without serious adverse reaction.

Topics: Animals; Brain; Brain Chemistry; Brain Ischemia; Calcium Channel Blockers; Cerebral Infarction; Drug Synergism; Flunarizine; Gerbillinae; Lamotrigine; Male; Neuroprotective Agents; Sodium Channels; Triazines

Topics: Adenosine Triphosphate; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Flunarizine; Humans; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Time Factors

21-day-old rats were subjected to unilateral carotid ligation, then, after 2 h of recovery, to 2 h of 8% hypoxia. Immediately following the insult they were treated with either flunarizine (30 mg/kg, i.p.) or with an equal volume of diluent. We have previously shown similar doses of flunarizine to be neuroprotective when given preinsult. After 5 days they were sacrificed for histological analysis. Cerebral injury was almost entirely confined to the ligated side. Full-thickness cortical infarction was noted in 55% of controls (n = 29) versus 36% of flunarizine-treated rats (n = 28; p = 0.14). Mean damage scores for all areas assessed including cortex, striatum, and hippocampus were not significantly different. These observations suggest that flunarizine is not significantly neuroprotective when given immediately after severe hypoxia-ischemia.

Topics: Animals; Animals, Newborn; Brain Ischemia; Cerebral Infarction; Dose-Response Relationship, Drug; Flunarizine; Hypoxia; Prosencephalon; Rats; Rats, Wistar

Unilateral photochemical infarcts were produced in the hind limb sensorimotor neocortex of 243 rats by intravenous injection of the fluorescein derivative Rose Bengal and focal illumination of the intact skull surface. Facial contact stimuli governed the degree and recovery rate of contralateral tactile/proprioceptive forelimb placing reactions. Contralateral forelimb placing recovered, whereas hind limb placing was resistant to recovery. Infarcted rats displayed marked recovery of spontaneous limb usage (beam traversing). However, deficits in isolated tactile/proprioceptive hind limb placing reactions endured. Posttreatment with the class IV calcium antagonist flunarizine after neocortical infarction protected sensorimotor function in a dose-dependent manner. This protective effect may be due to the peculiar ionic channel blocking profile of flunarizine. Scopolamine hydrobromide reinstated contralateral placing errors in infarcted rats at a dosage that did not affect neurologically intact rats. The cognitive enhancer sabeluzole, a novel benzothiazol derivative, dose-dependently blocked the anticholinergic-induced deterioration of a sensorimotor deficit in rats.

Topics: Animals; Calcium Channel Blockers; Cerebral Infarction; Flunarizine; Male; Movement; Nervous System; Physical Stimulation; Piperidines; Rats; Rats, Inbred Strains; Scopolamine; Somatosensory Cortex; Thiazoles

A rat cardiopulmonary arrest model was used to study the effects of flunarizine on survival and on the development of postischemic brain damage. Ischemia was induced by a combination of hypovolemia and intracardiac injection of a cold potassiumchloride solution. To validate the model; survival rate and histological damage were assessed after ischemic periods ranging from 5 to 20 minutes. A 6-minute cardiac arrest period was withheld for further therapeutic investigations. In one group (n = 12), flunarizine was administered successively in doses of 0.5 mg/kg intravenous at 5 minutes, 10 mg/kg intraperitoneal at 1 hour, and 20 mg/kg orally at 16 and 24 hours after recirculation. The second group (n = 13) received only the vehicle. Flunarizine, although not affecting mortality; significantly reduced the mean number of ischemic neurons in CA1 hippocampus from 83% in the control to 44% in the drug-treated series (P = 0.014). The results are indicative of the usefulness of this cardiac arrest model to study morphologic aspects of cerebral injury. The results obtained with flunarizine show the effectiveness of this drug even when it is administered after a severe ischemic insult such as global complete ischemia.

Topics: Animals; Cell Survival; Cerebral Infarction; Disease Models, Animal; Flunarizine; Heart Arrest; Hippocampus; Male; Neurons; Rats; Rats, Inbred Strains; Resuscitation; Shock; Time Factors

Topics: Calcium Channel Blockers; Cerebral Infarction; Cerebrovascular Disorders; Epilepsy; Flunarizine; Humans; Intracranial Arteriosclerosis; Migraine Disorders; Nimodipine

We produced unilateral photochemical infarcts in the hindlimb sensorimotor neocortex of 186 rats by intravenous injection of the fluorescein derivative rose bengal and focal illumination of the intact skull surface. Infarcted rats showed specific, long-lasting deficits in tactile and proprioceptive placing reactions of the contralateral limbs, mostly the hindlimb. Placing deficits were most prominent during transition to immobility and/or when independent limb movements were required. Administration of flunarizine, a Class IV calcium antagonist, 30 minutes after infarction resulted in marked sparing of sensorimotor function in 30 rats. In contrast to 20 vehicle-treated rats, which remained deficient for at least 21 days, 15 (75%) of the rats treated with 1.25 mg/kg i.v. flunarizine showed normal placing on Day 1 after infarction, whereas the remaining five (25%) recovered within 5 days. Oral treatment of 10 rats with 40 mg/kg flunarizine was also effective. Neocortical infarct volume and thalamic gliosis, assessed 21 days after infarction, did not differ between 30 flunarizine- and 30 vehicle-treated rats. However, when 4-hour-old infarcts were measured in 16 rats, posttreatment with intravenous flunarizine reduced infarct size by 31%. In combination with appropriate behavioral analyses, photochemical thrombosis may constitute a relevant stroke model, in which flunarizine preserved behavioral function during a critical period, corresponding to the spread of ischemic damage.

Topics: Animals; Cerebral Infarction; Disease Models, Animal; Flunarizine; Hindlimb; Light; Male; Motor Cortex; Proprioception; Psychomotor Performance; Rats; Rats, Inbred Strains; Rose Bengal; Time Factors; Touch

In an open pilot study 55 patients suffering from acute stroke were treated with Flunarizine, a calcium overload blocker, in addition to standard therapy including diet, physiotherapy, adequate management of accompanying disorders, and hemodilution. The initial high-dose i.v. treatment (2 X 25 mg Flunarizine/day) and the subsequent oral regimen were well-tolerated. The main side effect was slight transient weariness. No adverse effects regarding blood pressure, heart rate, enzymes, blood analysis, renal function and, especially, no extrapyramidal motor symptoms or depression were detected. Flunarizine may be regarded as a relatively safe drug in acute stroke. The probable beneficial effect on the patient's recovery will be evaluated in a multicenter double-blind study.

Topics: Aged; Aged, 80 and over; Cerebral Infarction; Drug Administration Schedule; Female; Flunarizine; Humans; Infusions, Intravenous; Male; Middle Aged; Pilot Projects

Topics: Animals; Calcium Channel Blockers; Cerebral Infarction; Cinnarizine; Flunarizine; Intracranial Arteriosclerosis