Ischaemic posterior circulation stroke in State of Qatar.

BACKGROUND: Ischaemic stroke features may show regional differences. Posterior circulation stroke (PCS) is of special interest, as symptomatology, course and outcome are usually different and complex. No significant studies or registries have reported on the characteristics and outcomes of PCS in our region. METHODS: We prospectively collected data of 116 patients with PCS admitted from 2005 through 2008 in the only stroke admitting hospital in Qatar. Demographics, risk factors, clinical signs/symptoms, pattern of presentation, aetiology, imaging features, complications and outcome at discharge and follow-up were recorded. RESULTS: Mean age was 53 years with 25% aged < or = 45, 85% were males. Demographically 47% were Arabs and 51% of South-Asian origin. Mean duration from onset to presentation was 29 h. Major risk factors were obesity (66%) and hypertension (61%). Minimal or fluctuating symptoms were present in 64%, while 9% had maximal deficit at onset. Thirty nine per cent had lesions in proximal territory and 23% in multiple territories. Around 41% had no occlusion, 16% had vertebro-basilar, 16% vertebral, 8% basilar occlusion. Etiologically 53% patients had large artery disease, 16% small vessel disease, and 17% cardioembolism. Seventy per cent of patients were discharged home, while 10% expired. Modified Rankin score (mRS) at discharge was < or = 2 in 53% and > or = 4 in 13% patients. At 30-day follow-up, 68% had mRS of < or = 2. Ninety-day survival status showed 89% alive with mRS < or = 2 in 73%. CONCLUSION: The aetiology and lesion topography of PCS in this heterogeneous population differs from the pattern observed in other populations.

The level of awareness of stroke risk factors and symptoms in the Gulf Cooperation Council countries: Gulf Cooperation Council stroke awareness study.

OBJECTIVE: To assess the knowledge of stroke in the general public in the Gulf Cooperation Council (GCC) countries. BACKGROUND: The Arabian Gulf is a rapidly developing part of the world with major changes in the lifestyle that can increase the risk of stroke. To design effective stroke treatment and prevention strategies, an assessment of the public knowledge of stroke is required. METHODS: A cross-sectional community-based survey was conducted at primary health care centers (PHCs), in urban and semi-urban areas, of the GCC countries (Qatar, Saudi Arabia, Kuwait, Bahrain, the United Arab Emirates, Oman) on the level of stroke awareness in the general public. Health care workers completed 3,750 face-to-face interviews. RESULTS: 1,089 (29.0%) were familiar with the term 'stroke', and 29.3% considered the age group 30-50 at the highest risk for stroke. The commonest risk factors identified were hypertension (23.1%) and smoking (27.3%). People who did not know the term stroke had a higher incidence of diabetes, hypertension, and had more than one risk factor (p < 0.05). The most frequently identified stroke symptoms were weakness (23%) and speech problems (21.7%). Of those who recognized stroke, blockage of blood vessels was identified as the commonest cause of stroke (22%) followed by tension/worrying (20%). Doctors and nurses were regarded as the best source of stroke information (70%). In the univariate comparison, younger age (p < 0.001), higher level of education (p < 0.001), and female gender (p = 0.008) better predicted stroke recognition. In a multivariate logistic regression analysis, the level of education, monthly income and smoking were independent variables predicting stroke knowledge. CONCLUSION: The majority of the patients had not even heard the term stroke. Stroke knowledge was poorest among the groups that were at the highest risk for stroke. Stroke education has to focus on the high-risk groups, particularly the younger population. The health care workers at the PHCs and hospitals will need instructions on providing stroke information to the public. The level of knowledge of stroke risk factors and symptoms emphasizes the need for stroke education efforts in the community.

Pure isolated unilateral internuclear ophthalmoplegia from ischemic origin: report of a case and literature review.

PURPOSE: To report a case of pure isolated unilateral internuclear ophthalmoplegia from ischemic stroke, and to review its literature. METHODS: A 55-year old man, with a history of long-standing diabetes mellitus, developed acute-onset left internuclear ophthalmoplegia. MRI revealed a small paramedian dorsal pontine infarct ventral and lateral to the aquaductus cerebri. Intracranial MR angiography was normal. A systematic search was performed of the literature from January 1980 to December 2004 by using MEDLINE and EMBASE. Case reports with or series including patients with negative MRI findings were excluded. RESULTS: Nine cases of pure isolated MRI-proven unilateral INO resulting from ischemic stroke including this one, have been reported. In over 75% recovery was reported. CONCLUSION: Isolated unilateral internuclear ophthalmoplegia can be the sole manifestation of ischemic stroke and generally carries a good prognosis.

Vertical one-and-a-half syndrome. Supranuclear downgaze paralysis with monocular elevation palsy.

A patient with bilateral infarction in the mesodiencephalic region showed impairment of all downward rapid eye movements (including vestibulo-ocular movements) and foveal smooth pursuit (nondissociated downgaze paralysis) associated with monocular paralysis of elevation (vertical one-and-a-half syndrome). Bell's phenomenon and all types of horizontal eye movements were preserved. The lesions may have affected the efferent tracts of the rostral interstitial nucleus of the medial longitudinal fasciculus bilaterally and the premotor fibers to the contralateral superior rectus subnucleus and ipsilateral inferior oblique subnucleus, either before or after decussation in the posterior commissure.

Dissociated ipsilateral horizontal gaze palsy in one-and-a-half syndrome: a clinicopathologic study.

We report a patient with a one-and-a-half syndrome due to an isolated small infarction in the left rostral part of the paramedian pontine reticular formation and the ipsilateral medial longitudinal fasciculus. Oculocephalic movements toward the left were preserved (dissociated ipsilateral horizontal conjugate gaze palsy).

Controlled-release carbidopa/levodopa (CR) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations.

The efficacy of an oral controlled-release preparation of carbidopa/levodopa (Sinemet CR 50/200 mg) was compared with conventional carbidopa/levodopa (25/250 mg) in an open-label study. Twenty patients with idiopathic Parkinson's disease and severe response fluctuations participated. At the end of 6 months of CR treatment, the major clinical benefits included improvement of disability, reduction in number of "off" periods (predominantly end-of-dose hypokinesia), and increase in percentage of "on" time. Although dosages of CR required for an optimal therapeutic response were not significantly higher compared with conventional levodopa, bioavailability significantly increased. Delayed onset of antiparkinsonian effect of CR, resulting from an increase of Tmax for levodopa, was one of the major patient complaints and required additional small amounts of standard levodopa in some patients.

Current and emerging second-generation triptans in acute migraine therapy: a comparative review.

Sterile neurogenic inflammation within cephalic tissue, involving vasodilation and plasma protein extravasation, has been proposed as a pathophysiological mechanism in acute migraine. The action of 5-hydroxytryptamine (5-HT1B/1D) agonists--so-called triptans--on receptors located in meningeal arteries (5-HT1B) and trigeminovascular fiber endings (5-HT1D) has an inhibitory effect on this neurogenic inflammation. Recently, a series of second-generation 5-HT1B/1D agonists (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and zolmitriptan) have been developed and are reviewed in this article. Their in vitro pharmacological properties, pharmacokinetics, clinical efficacy, drug interactions, and adverse effects are evaluated and compared to the golden standard in the treatment of acute migraine, sumatriptan.

The effect of carbidopa on the pharmacokinetics and metabolism of intravenously administered levodopa in blood plasma and skeletal muscle.

The effect of carbidopa on the pharmacokinetics and metabolism of levodopa (L-dopa) in blood plasma and skeletal muscle extracellular fluid (ECF) has been studied by repeated measurements in one beagle dog. The administration of a single dose of L-dopa (25 mg/kg i.v.) without carbidopa pretreatment (controls) resulted in an increase in the concentrations of L-dopa and 3-O-methyldopa (3-OMD) in blood plasma and skeletal muscle ECF dialysates. This effect was clearly potentiated for L-dopa in blood plasma (186% increase in AUC) and 3-OMD in skeletal muscle dialysates (108% increase in AUC) after pretreatment with carbidopa (100 mg/day). In addition, carbidopa prolonged the half-life of the elimination of L-dopa in blood plasma by 48% and in skeletal muscle ECF by 66% but did not influence its blood plasma distribution half-life (t 1/2 alpha = 0.17 h). The elimination half-life of L-dopa in the controls was higher in muscle (t 1/2 beta = 1.76 h) than in blood plasma (t 1/2 beta = 0.50 h). Carbidopa pretreatment resulted in a relatively small increase (29%) in the L-dopa content of skeletal muscle ECF as indicated by the AUC. The accumulation of 3-OMD in muscle dialysates, in contrast to that in plasma, was significantly enhanced after the administration of L-dopa following treatment with carbidopa. In the control experiments, dopamine (DA) was detectable only in the dialysates from muscle ECF.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle. A microdialysis study.

In the present study in vivo microdialysis sampling coupled to high-performance liquid chromatography with electrochemical detection, was used to study the pharmacokinetics of levodopa and 3-O-methyldopa in skeletal muscle in dog, after intravenous administration of levodopa. For comparison, the pharmacokinetic parameters of both compounds were simultaneously determined in plasma using blood collection. Muscle microdialysis samples and blood were continuously collected for 4 h after the administration of levodopa (25 mg/kg). Pharmacokinetic profiles of levodopa in plasma and muscle were different. The mean Tmax value of levodopa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf for levodopa in plasma was nearly 18-fold higher in plasma than in muscle. The 3-O-methyldopa concentration increased very rapidly after the administration of levodopa, to reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 for 3-O-methyldopa was 3.6-fold higher in plasma than in muscle. The ratio levodopa/3-O-methyldopa, reflecting the metabolic rate of levodopa, was 3.5 times higher in plasma than in muscle, at the peak value of levodopa, and then rapidly declined to values lower than 1, one hour after administration of the drug. We compared our results with literature data from postmortem studies done in rat experiments. We concluded that levodopa is not accumulating in muscle as such, but is converted to 3-O-methyldopa probably before leaving the plasma compartment.

Biotransformation of L-dopa in striatum and substantia nigra of rats with a unilateral, nigrostriatal lesion: a microdialysis study.

Microdialysis was used to study the biotransformation of L-DOPA in the striatum and substantia nigra of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. The animals were pretreated with carbidopa (50 mg/kg p.o.) for 5 days. They were anaesthetized, and microdialysis probes were implanted into the intact and denervated striatum and into the intact and lesioned substantia nigra. The biotransformation of L-DOPA (5 mg/kg i.p.) in these regions was investigated. These results were compared with those obtained after administration of a much higher dose of L-DOPA (100 mg/kg i.p.). Changes in extracellular L-DOPA, 3-O-methyldopa (3-OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC with electrochemical detection. Although rats with a unilateral nigrostriatal lesion did not show rotational behaviour after 5 mg/kg L-DOPA, DA levels were increased significantly both in the intact and the denervated striatum and in the intact and the lesioned substantia nigra. This increase was most pronounced in the denervated striatum. At 100 mg/kg L-DOPA, the increases in extracellular dopamine in intact and denervated striatum were about twice as high as the increases observed at the lower dose. A similar increase was observed in the intact substantia nigra. However, in the lesioned substantia nigra there was a fourfold increase. L-DOPA, at both doses, was evenly distributed between the brain areas studied and the lesion had no effect on the uptake of the drug at the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Symptomatic and prophylactic treatment of migraine: a critical reappraisal.

The pharmacologic management of migraine has traditionally focused on two approaches: symptomatic treatment and prophylactic therapy. The objective of symptomatic treatment is to reduce the intensity and duration of pain with its attendant symptoms and to optimize the patient's ability to function normally. The efficacy of most abortive antimigrainous drugs in probably related to their inhibitory effects on neurogenic inflammation mediated through serotoninergic control mechanisms. A variety of treatment strategies provide effective treatment for most attacks of moderate to severe migraine when utilizing one or a combination of the following classes of drugs: simple analgesics, nonsteroidal anti-inflammatory drugs, antiemetics, narcotic analgesics, ergot derivatives, and serotonin1-agonists. The choice of medication for an acute attack depends on factors such as the severity of the attack, the presence or absence of vomiting, time from onset of pain to peak pain level, rate of bioavailability of the drug, comorbid medical conditions, and the side effect profile of the drug. The major objective of prophylactic therapy is the reduction of frequency, duration, and intensity of attacks. Beta-blocking drugs without intrinsic sympathomimetic activity (such as propranolol), amitriptyline, flunarizine, serotonin antagonists (such as methysergide) and nonsteroidal anti-inflammatory drugs (such as naproxen) are the five main classes of drugs or agents that may be used as prophylactics.

Simultaneous in vivo microdialysis in plasma and skeletal muscle: a study of the pharmacokinetic properties of levodopa by noncompartmental analysis.

This in vivo study compared the pharmacokinetics of intravenously (iv) administered levodopa (L-dopa) in plasma and skeletal muscle. For this purpose, a single iv dose of L-dopa (25 mg/kg) was given to an anesthetized beagle dog, and L-dopa as well as its O-methyl metabolite, 3-O-methyldopa (3-OMD), were monitored in plasma and skeletal muscle simultaneously by microdialysis. The plasma and muscle dialysates were continuously collected during a 3-h period after the iv administration of the drug. The pharmacokinetic variables were then compared in both tissues with noncompartmental modeling. The mean maximum concentration (Cmax) for L-dopa in plasma was 173.10 +/- 9.85 ng/mL, whereas in skeletal muscle extracellular fluid, it was 14.56 +/- 2.27 ng/mL. The area under the curve of concentration versus time from time zero to infinity (AUC0- > inf) values for L-dopa were 20 times higher in plasma compared with muscle. The difference in half-life between the two tissues probably indicated the large contribution of the distribution phase in either or both tissues over the 3-h time interval. Interestingly enough, the AUC0- > 3h values for 3-OMD were within the same range in both tissues. These data demonstrated that over a period of 3 h, no distribution equilibrium for L-dopa was reached over the two tissues. The very low L-dopa/3-OMD ratios suggested that, in contrast to L-dopa, 3-OMD is accumulating in skeletal muscle. Whether these findings have any implication for the therapeutic response to L-dopa in Parkinson's disease remains to be determined.

Clinical and pharmacokinetic evaluation of controlled-release levodopa/carbidopa (CR-4) in parkinsonian patients with severe motor fluctuations: a six month follow-up study.

The results of a six month open-label study comparing the efficacy of controlled-release levodopa-carbidopa (Sinemet CR-4 200 mg/50 mg) with standard levodopa/carbidopa (250 mg/25 mg) in 17 patients with idiopathic Parkinson's disease and severe response fluctuations, are reported. Major clinical benefits included; improvement of disability, reduction of the number of 'off' periods (predominantly end-of-dose hypokinesia) and a slight increase in 'on' time. No improvement was observed in two of our patients. Mean levodopa plasma levels were comparable between the two types of formulations during optimal treatment, however systemic bioavailability was significantly higher with CR-4. Delayed onset of antiparkinsonian effect of CR-4, resulting from an increase of Tmax for levodopa, was one of the major complaints and required additional small amounts of standard levodopa in three patients.

Recurrent forms of sporadic brachial plexus neuropathy. A report of two cases.

Two patients presenting a relapsing form of sporadic brachial plexus neuropathy, the so-called Parsonage Turner syndrome, are reported. The diagnosis is based on clinical and electromyographic features. Recurrent attacks, although infrequently encountered, have been well described in the past. Sporadic cases of this syndrome must be differentiated from the familial varieties of neuralgic amyotrophy in which, two main subgroups of patients are distinguished: those showing facial dysmorphic features and those with findings of a tomaculous neuropathy predisposing them to pressure palsies. Apart from the obvious difference as regards familial occurrence, the familial and non-familial varieties of neuralgic amyotrophy differ in a number of respects: associated congenital defects, early age of onset and high rate of recurrence in the former. Finally some possible pathogenetic mechanisms of the syndrome are briefly reviewed.

Simultaneous monitoring of levodopa, dopamine and their metabolites in skeletal muscle and subcutaneous tissue in different pharmacological conditions using microdialysis.

Microdialysis, in combination with ion-pair reversed-phase liquid chromatography and electrochemical detection is described for the simultaneous determination of levodopa, dopamine, 3-O-methyldopa and 3,4-dihydroxyphenylacetic acid in the extracellular space of skeletal muscle and subcutaneous tissue in vivo in beagle dog. The relative recoveries in vitro for levodopa, dopamine, 3-O-methyldopa and 3,4-dihydroxyphenylacetic acid with a 16 mm probe at a flow rate of 5 microliters min-1 were 29.1, 25.1, 34.7 and 30.1%, respectively. This technique was then applied for three types of pharmacological experiments. In the first experiment L-dopa was administered without carbidopa pretreatment, in the second one, L-dopa was administered following carbidopa pretreatment, and in the last experiment, following pretreatment with both carbidopa and the catechol-O-methyltransferase inhibitor, OR-611. After the administration of levodopa without carbidopa pretreatment, all four compounds could be detected in dialysates from skeletal muscle, whereas dopamine and 3,4-dihydroxyphenylacetic acid were not found in dialysates from subcutaneous tissue. After the administration of levodopa following carbidopa pretreatment and following pretreatment with both carbidopa and OR-611 all compounds could be measured except for dopamine. This method enables the pharmacokinetics and metabolism of levodopa to be studied in subcutaneous tissue and skeletal muscle simultaneously.

Simultaneous determination of levodopa, carbidopa, 3-O-methyldopa and dopamine in plasma using high-performance liquid chromatography with electrochemical detection.

An analytical method is described which allows a fast, reliable and precise determination of levodopa and its metabolises 3-O-methyldopa and dopamine, as well as the peripheral aromatic amino acid decarboxylase inhibitor carbidopa, in a single 1 ml plasma sample of Parkinsonian patients. The compounds are quantitatively isolated on small Sephadex G-10 columns and determined by HPLC with electrochemical detection. Dihydroxybenzylamine or alpha-methyldopa are used as the internal standard. An example of therapeutic drug monitoring in a patient with fluctuations in motor performances is given. It is confirmed that interference with absorption of levodopa from the stomach by food can be partly responsible for these observed fluctuations.

Continuous intravenous monitoring of levodopa and 3-O-methyldopa by microdialysis and high-performance liquid chromatography with electrochemical detection.

Microdialysis, in association with ion-pair reversed-phase high-performance liquid chromatography with electrochemical detection, was applied in vitro for the determination and quantification of levodopa and 3-O-methyldopa in blank spiked plasma and blood. The method presented gave accurate results; the calibration graphs for plasma were linear over the range of the expected values for both compounds. When using a dialysis probe with a membrane length of 1.6 cm at a 5 microliters min-1 perfusion speed, the recovery rate in plasma for levodopa was 30.1% and 68.5% for 3-O-methyldopa. However, less reproducible results were obtained for plasma levodopa levels in the range of 0.5 microliter ml-1 and lower. The microdialysis technique was subsequently successfully applied for the continuous intravenous monitoring of levodopa and 3-O-methyldopa in a levodopa-treated dogs.

Detection of muscle necrosis in dermatomyositis by 111In-labelled antimyosin Fab fragments.

This paper presents the findings on two patients with a final diagnosis of dermatomyositis in whom 111In-antimyosin imaging revealed diffuse muscle necrosis of the limbs. The potential application of this scintigraphic procedure for diagnosis and follow-up of patients with dermatomyositis-polymyositis is addressed.

Spinal osteomyelitis: an unusual complication in aortic graft surgery.

The case history of a patient with vertebral osteomyelitis due to a contiguous paraprosthetic aortic abscess is reported. This unusual complication may be associated with the indolent nature of paraprosthetic aortic infections. The diagnostic as well as therapeutic value of computerised tomography in this condition is emphasized.