Regional cerebral blood flow following single-dose and continuous-dose tadalafil after stroke.

PURPOSE: Tadalafil is a potent and selective phosphodiesterase type 5 inhibitor that provides effective treatment for erectile dysfunction (ED). The purpose of this study was to explore the effect of a single on-demand dose of tadalafil compared to low-dose continuous administration on regional cerebral blood flow (rCBF), in patients after stroke. METHODS: Thirty consecutive male patients (mean age 58.3 ± 7.9 years) with ED and a history of stroke were included in the study. The baseline single-photon emission computed tomography (SPECT) study was performed 15 min after iv injection of 740 MBq Tc-99m-HMPAO (Ceretec; GE Healthcare Ltd. Chalfont St. Giles, UK). Fifteen randomized patients received a single dose of 20 mg tadalafil in the morning, and a second SPECT study was performed 6 h later. Fifteen other patients received 5 mg of tadalafil each morning for seven consecutive days, and the second SPECT study was performed 6 h after the last dose. The imaging data were evaluated using SPM software (Wellcome Department of Cognitive Neurology, University College, London). RESULTS: Associations between any of the risk factors/comorbidities and the perfusion changes were not detected. All patients showed areas of reduced relative rCBF in the affected hemisphere after tadalafil administration compared to baseline (P < 0.001). No significant difference was found between patients on 5 mg tadalafil and 20 mg dose. CONCLUSION: Tadalafil administration after cerebral stroke may be associated with diminished blood flow to areas adjacent to the stroke. The alterations in perfusion suggest a need for caution in prescribing tadalafil to patients with a history of stroke, especially with continuous administration that may impose constant stress on the cerebral circulation.

The effect of sildenafil citrate (Viagra) on cerebral blood flow in patients with cerebrovascular risk factors.

OBJECTIVES: Sildenafil citrate is widely used for erectile dysfunction. The present study examined the short-term effects of sildenafil administration in individuals with cerebrovascular risk factors, including patients with a history of stroke. MATERIALS AND METHODS: Twenty-five consecutive male patients with erectile dysfunction and vascular risk factors were included in the study. A perfusion brain SPECT study was performed at baseline and 1 h after the oral administration of sildenafil. RESULTS: Associations between any of the risk factors and the perfusion scores were not detected, with the exception of stroke. Stroke patients showed significantly more areas with diminished perfusion after sildenafil administration compared to baseline. CONCLUSIONS: In patients with diabetes or hypertension, a dose of 50 mg sildenafil does not appear to produce detrimental effects on cerebral blood flow. However, patients with a history of stroke may be at increased risk of hemodynamic impairment after the use of sildenafil.

Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin.

OBJECTIVE: To evaluate the efficacy and tolerability of the treatment with valproic acid (VPA) in patients with status epilepticus (SE) or acute repetitive seizures (ARS) comparing it with phenytoin (PHT) treatment. MATERIALS AND METHODS: Patients with SE or ARS were treated in a consecutive manner with either VPA or PHT intravenously. The primary endpoint was defined as clinical seizure cessation; the secondary endpoint was evaluation of drug tolerability. RESULTS: Seventy-four adult patients with SE or ARS participated in the study, 49 with VPA i.v. and 25 PHT i.v. In 43 (87.8%) of the VPA patients, the seizures discontinued, and no rescue medication was needed. Similar results were found in the PHT group in which seizures of 22 (88%) patients were well controlled. Side effects were found in 12% of the PHT group, and in none of the VPA group. CONCLUSIONS: VPA i.v. seems to be effective and well tolerated in adult patients with SE or ARS.

Minocycline treatment in acute stroke: an open-label, evaluator-blinded study.

BACKGROUND: Ischemic animal model studies have shown a neuroprotective effect of minocycline. OBJECTIVE: To analyze the effect of minocycline treatment in human acute ischemic stroke. METHODS: We performed an open-label, evaluator-blinded study. Minocycline at a dosage of 200 mg was administered orally for 5 days. The therapeutic window of time was 6 to 24 hours after onset of stroke. Data from NIH Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) were evaluated. The primary objective was to compare changes from baseline to day 90 in NIHSS in the minocycline group vs placebo. RESULTS: One hundred fifty-two patients were included in the study. Seventy-four patients received minocycline treatment, and 77 received placebo. NIHSS and mRS were significantly lower and BI scores were significantly higher in minocycline-treated patients. This pattern was already apparent on day 7 and day 30 of follow-up. Deaths, myocardial infarctions, recurrent strokes, and hemorrhagic transformations during follow-up did not differ by treatment group. CONCLUSIONS: Patients with acute stroke had significantly better outcome with minocycline treatment compared with placebo. The findings suggest a potential benefit of minocycline in acute ischemic stroke.

Annexin V SPECT imaging of phosphatidylserine expression in patients with dementia.

The authors sought to use radiolabeled annexin V, a marker of phosphatidylserine expression, to image Alzheimer dementia (AD). Four of five patients with AD had multifocal cortical annexin V uptake, whereas all seven non-AD and six control patients had normal SPECT. The mean cortex/cerebellar activity in patients with AD (1.4 +/- 0.6) was higher than that of non-AD dementia patients (0.7 +/- 0.2; p = 0.02). Radiolabeled annexin V may be useful for imaging AD.

Transient global amnesia -- not always a benign process.

OBJECTIVES: Transient global amnesia (TGA) is an episodic dysfunction of declarative memory, which is assumed to be a benign disorder. Brain perfusion single photon emission computed tomography (SPECT) was shown to be abnormal during the acute stage and to become normal with normalization of memory function. No data are known about the brain perfusion pattern among these patients with recurrent TGA. MATERIAL AND METHODS: Sixteen patients with TGA were studied with an initial brain imaging during the acute stages of their attack, and a second imaging was performed after 3 months. In the event of a patients having a second abnormal brain perfusion HMPAO SPECT, a third imaging was performed after 1 year. RESULTS: Hypofusion perfusion was demonstrated in all cases during the acute stage. In all patients who had a first TGA, a normal SPECT was demonstrated after 3 months. In three patients with recurrent TGA, the brain perfusion remained abnormal after 3 months and after 1 year. CONCLUSIONS: A normal perfusion in TGA after 3 months can be expected in a patient with a first attack. In patients with recurrent TGA attacks, a persistent focal hypoperfusion can be expected. This subgroup of patients may demonstrate a non-benign type of TGA, eventually due to a different etiology of event.

Optic neuritis complicating west nile virus meningitis in a young adult.

A case of West Nile virus (WNV) infection with meningitis and optic neuritis in a 28-year-old man is presented. The patient had a number of unusual clinical and laboratory findings that broadened the differential diagnosis. The emergence of WNV infection in southern Europe and North America calls for increased awareness of physicians to this clinical entity.

Serum leptin level in women with idiopathic intracranial hypertension.

Leptin is a protein secreted by adipose cells which influences regulation of energy balance and body weight. Idiopathic intracranial hypertension (IIH) is recognised as a neurological disorder mainly affecting obese females. The aim of this study was to evaluate the association between IIH and serum leptin level in 15 obese patients and compare the results with those for 16 obese and 15 non-obese women. A significantly higher serum leptin level was found in patients with IIH than in controls (p<0.0001), and this did not correlate with body mass index (BMI). Serum leptin levels were significantly associated with BMI in both control groups (p<0.0006). Additional factors must therefore be involved in the phenomenon of serum leptin increase beyond weight gain. The cause can only be hypothesised, but it seems that the origin is central, probably hypothalamic.

Cerebrovascular reactivity in patients under long-term acetazolamide treatment.

BACKGROUND AND PURPOSE: The acetazolamide (AZA) test is a well-accepted method for measuring the vascular reactivity of the cerebral arteries. In order to investigate the nature of this reactivity after long-term daily AZA treatment, the cerebral blood velocity (CBV) was measured using transcranial Doppler in patients under continuous AZA treatment after a single AZA 1 g intravenous (IV) dose. METHODS: Thirteen patients (eight women, five men) on long-term daily AZA (750 mg/day, mean treatment duration 68 +/- 12+ months) were included in the study. The CBV of the middle cerebral artery (MCA) and the basilar artery (BA), including the values of peak velocity, mean velocity and pulsatility index (PI) were measured. The examination was performed twice - with the initial IV administration of AZA and 20 min later. The results were compared with those of 10 age matched volunteers. RESULTS: A consistent significant increase of CBV in the right and left MCA (P < 0.001 for both arteries) was found in all study participants. A highly significant decrease of peak CBV in the BA (P < 0.001) was found in the post-AZA velocities of the patient's group. In the control group, a consistent significant increase in all post-AZA tests was demonstrated (P < 0.001). CONCLUSIONS: A mild elevation of blood velocity in the MCAs concomitant with a highly significant decrease of velocity in the BA was present in all examined patients. These patterns of CBV changes indicate the presence of a 'steal phenomenon' from the posterior to the anterior circulation and stress the necessity for caution when evaluating the indications for performance of the AZA test in patients under continuous AZA therapy.

Antiepileptic treatment in patients with early postischemic stroke seizures: a retrospective study.

Early seizures caused by stroke are a common cause of epilepsy in adults. The protocol for treatment in such a case is not clear. Patients were studied retrospectively after early poststroke seizures. Two groups of patients were compared: one treated group included 35 patients who continued therapy for 2 years; the second group of 23 patients were untreated following a first attack, receiving anticonvulsive therapy only after a second seizure. The data of 61 patients (35 treated and 26 untreated) were analyzed. In the treated group, 24 patients were on treatment with carbamazepine, 9 with valproic acid and 2 with phenytoin. Seizure-free rate after 2 years was 85% in group I and 61% in group II (p = 0.042). Comparing the seizure rate and the event-free period (number/follow-up at risk) during the 2 years of no anticonvulsive therapy, both groups experienced about the same seizure rate (4.8 vs. 6.2%, p = 0.605) and similar seizure-free curve survival analysis (p = 0.85). We conclude that treatment of seizures immediately after the first attack after cerebral infarctions decreases the risk of recurrent seizure during the first 2 years of antiepileptic treatment. This subgroup of patients receiving antiepileptic medication immediately after the first poststroke seizure continues to be at the same rate of risk after treatment was stopped as the untreated group during the first 2 years. Antiepileptic therapy is an option in the medical management of poststroke seizure patients, but has no influence on the development of recurrent seizures after discontinuing medication.

Benign intracranial hypertension: correlation of cerebral blood flow with disease severity.

UNLABELLED: Benign intracranial hypertension (BIH) is characterized by symptoms and signs of raised intracranial pressure in the absence of an intracranial mass lesion, infection or hydrocephalus. The purpose of this study was to evaluate the effect of disease severity on cerebral blood flow in patients with BIH on acetazolamide therapy. METHODS: 11 patients (nine females, two males; mean age 30.5 years; range 22-29 years) with BIH were studied. All patients underwent CT and MRI scanning which were normal. The CSF pressure of all patients was above 200 mm H2O. All patients were under treatment with acetazolamide (1 g/day). Disease severity was determined by visual field examination and by clinical symptoms. Five patients were categorized into mild to moderate BIH (group I) and six patients had severe BIH (group II). All patients underwent perfusion brain SPECT with 740 MBq of Tc-99m-HMPAO. RESULTS: Brain perfusion abnormalities were observed in six of the 11 patients. One out of five patients in group I (20%) and five out of six patients (83%) in group II, had abnormal SPECT findings (P<0.04). In four patients of group II the left parietal lobe was involved and another patient had a right occipital abnormality. The single patient from group I with SPECT abnormalities demonstrated focal decreased perfusion in the left temporal area and decreased perfusion in the left caudate nucleus. CONCLUSION: Patients with severe degree of BIH have a higher incidence of cerebral perfusion abnormalities. This group may have an increased risk of cerebrovascular complications. The continuous administration of acetazolamide which affects the vascular autoreactivity may contribute to the regional hypoperfusion. Further studies are recommended to evaluate the natural course of disease versus iatrogenic treatment effects.

Intravenous administration of magnesium sulfate in acute stroke: a randomized double-blind study.

A randomized, placebo-controlled, double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke. Patients who had cortical infarction in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included. The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator. Patients had follow-up for 30 days. The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale (80 points) and relative functional independence on the Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily living index and Rankin disability score were obtained on day 30. Forty-one patients (22 given treatment and 19 given placebo) demonstrated significant beneficial effects on the Orgogozo scale (84 +/- 11 vs. 64 +/- 10, p < 0.0001) and (83 +/- 14 vs. 70 +/- 15, p < 0.009), respectively. At the end of 1-month follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group (84 +/- 26 vs. 71.8 +/- 26, p < 0.143) than in control subjects (2.3 +/- 1.1 vs. 3 +/- 1.3, p < 0.077). Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke. Further studies on a larger scale are needed to confirm these findings.

Laboral outcome after acute unilateral vestibulopathy.

Sixty-five adult patients who had acute peripheral vestibulopathy (APV) were followed-up to determine their functional outcome. During the acute phase, they were treated with betahistine and mobilization. In the entire study population, APV was not significantly associated with a change in occupational activities, physical work or driving ability. Older individuals had significantly attributed a change in work to disease other than APV. Change attributed to APV occurred significantly more frequently in women than in men. The therapeutic approach seems beneficial.

Rhabdomyolysis induced by simvastatin and ketoconazole treatment.

Rhabdomyolysis is described as an adverse event of simvastatin therapy either by itself or in combination with other medications. It is unclear whether this phenomenon is specific to simvastatin or to all cholesterol-lowering agents as single-dose therapy or caused by the association of special coadministered medications. We describe two cases in which rhabdomyolysis developed after coadministration of simvastatin (20 mg/d) and the antifungal ketoconazole. The clinical features, blood examination results, and positive outcome were very similar in both cases. We concluded that ketoconazole, an antifungal sterol synthetic inhibitor of the azol group, may induce rhabdomyolysis in patients undergoing treatment with simvastatin, a lipid lowering agent, and increase the possibility of muscle-damaging adverse events of the agents.

Bilateral ptosis and changes in state of alertness in thalamic infarction.

Uni- or bilateral supranuclear ptosis is known to be caused by cerebral lesion. The exact anatomical cortical and subcortical basis is still undefined. We report a case of a patient developing bilateral ptosis with a left thalamic lesion. The bilateral ptosis was associated with transient changes in the state of alertness. We postulate that the thalamus, especially the anterior region, may have an influential role on the pathway from the cortex via the posterior branch of the internal capsule to the levator palpebrae superioris nuclei.

Self and body esteem perception in multiple sclerosis.

Self esteem and body esteem were examined in a group of 35 relapsing-remitting multiple sclerosis (MS) patients using the Body Esteem Scale (BES) and the Eysenck Self Esteem Scale (ESES) and compared to age and sex matched normal controls. There were 23 females and 12 males in the MS patient's group; average age 38.9 years (range: 22-52). All participants completed the self-rated BES evaluating the following subscales: females - sexual attractiveness, physical condition and weight concern; males - physical attractiveness, physical condition and upper body strength. In addition all participants were scored, following a semi-structured interview, on the ESES. Psychiatric co-morbidity was excluded using a semi-structured interview by the consulting psychiatrist. All evaluations were carried out during the remitting phase. Statistical analysis, comparing patients to healthy controls, demonstrated lowered self-rating of the physical condition (males < 0.05, females < 0.001). On the other hand, no significant differences were found in the physical (male) or sexual (female)�attractiveness subscales. The mean ESES score in the patients group was 23.2 ± 4.0, slightly above the reported average. The controls mean ESES was 28.4 ± 3.6, (P < 0.05). No correlation was found between self and body esteem amongst M.S. patients. This study emphasizes impaired perception of body esteem in multiple sclerosis patients even in remission. The preservation of physical and sexual attractiveness may be related to the non-disfiguring nature of the disease. Preservation of self-esteem in MS patients suggests that body-esteem should be the focus of supportive treatment.

Cerebrospinal fluid magnesium level as a prognostic factor in ischaemic stroke.

Magnesium has been reported to have a dilatatory effect on cerebral arteries. Reduction of extracellular Mg+2 has been shown to be directly correlated with the intensity of cerebral spasm. A neuroprotective effect of magnesium in stroke has also been hypothesized. The aim of our study was to examine the Mg+2 levels in serum and cerebrospinal fluid (CSF) in the early stage of stroke and to evaluate the correlation between Mg+2 levels and the development of neurological deficits. Between 1986 and 1994, 96 patients who had a stroke of 24- to 48-h duration were enrolled in the study. Serum and CSF levels of magnesium were checked on admission, 2448 h after the onset of stroke. Using a neurological score, the neurological deficit was assessed on the 1st day, 1 and 4 weeks later. Computed tomography (CT) was performed after 1 week, and the volume and location of infarction were calculated and measured. Statistical analysis was performed for cortical and subcortical patients separately, using Spearman correlation and multiple linear and logistic regression analyses. Significant correlation was found between CSF Mg+2 and the size of the infarct (P < 0.0001). There was no correlation between serum Mg+2 and CSF Mg+2 levels. Regression analysis demonstrated an increase in the values of the Mathew Neurological Score with higher CSF Mg+2 levels. This association remained true after other factors such as age, associated heart disease, diabetes and infarction size had been taken into account by the regression model. The results confirm that there is a relationship between a low Mg+2 concentration in CSF during the first 48 h after onset of ischaemic stroke and the intensity of the neurological deficit. The therapeutic consequence of this finding may have some importance.