Symptomatic idiopathic intracranial hypertension triggered by Ramadan intermittent fasting: a case report.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disorder that primarily affects obese women of reproductive age. The exact pathogenesis of IIH is unknown though multiple etiologies have been proposed. CASE PRESENTATION: We report a case of IIH triggered by first-time Ramadan intermittent fasting (RIF) in an 18-year-old woman. Our patient developed new onset headaches, diplopia, and pulsatile tinnitus with examination notable for bilateral papilledema and lumbar puncture revealing an elevated opening pressure. Her symptoms resolved after cessation of RIF, apart from persistent left sided tinnitus which later resolved with acetazolamide administration. CONCLUSION: This case report uniquely illustrates that RIF may provoke symptomatic IIH. We hypothesize that a decreased concentration of glucagon-like peptide-1 (GLP-1) induced by fasting results in decreased GLP-1 receptor activation in the choroid plexus, allowing for increased CSF secretion into the ventricles invoking increased intracranial pressure (ICP). This theoretical mechanism provides further insight as to the possible underlying pathophysiology of IIH.

Genetic variation at CR1 increases risk of cerebral amyloid angiopathy.

OBJECTIVE: Accumulated evidence suggests that a variant within the CR1 gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences ß-amyloid (Aß) deposition in brain tissue. Given the biologic overlap between AD and cerebral amyloid angiopathy (CAA), a leading cause of intracerebral hemorrhage (ICH) in elderly individuals, we investigated whether rs6656401 increases the risk of CAA-related ICH and influences vascular Aß deposition. METHODS: We performed a case-control genetic association study of 89 individuals with CAA-related ICH and 280 individuals with ICH unrelated to CAA and compared them with 324 ICH-free control subjects. We also investigated the effect of rs6656401 on risk of recurrent CAA-ICH in a prospective longitudinal cohort of ICH survivors. Finally, association with severity of histopathologic CAA was investigated in 544 autopsy specimens from 2 longitudinal studies of aging. RESULTS: rs6656401 was associated with CAA-ICH (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17, p = 8.0 × 10(-4)) as well as with risk of recurrent CAA-ICH (hazard ratio = 1.35, 95% CI 1.04-1.76, p = 0.024). Genotype at rs6656401 was also associated with severity of CAA pathology at autopsy (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Adjustment for parenchymal amyloid burden did not cancel this effect, suggesting that, despite the correlation between parenchymal and vascular amyloid pathology, CR1 acts independently on both processes, thus increasing risk of both AD and CAA. CONCLUSION: The CR1 variant rs6656401 influences risk and recurrence of CAA-ICH, as well as the severity of vascular amyloid deposition.

Boosting enrolment in clinical trials: validation of a regional network model.

BACKGROUND: Clinical trials of stroke therapy have been hampered by slow rates of enrolment. PURPOSE: Our purpose is to validate a previously developed model for accelerating enrolment in clinical trials by replicating it at new locations. The model employs coordinators who travel from a host institution to enrol participants from a network of participating hospitals. Active surveillance assures identification of all eligible patients. METHODS: Among 70 U.S. investigators participating in National Institutes of Health-funded trial of stroke prevention, five investigators were invited to develop local identification and outreach networks (LIONs). Each LION comprised a LION coordinating centre servicing multiple hospitals. Hospitals provided names of patients with stroke or transient ischaemic attack to researchers at the LION coordinating centre who initiated contact; patients were offered home visits for consent and randomization. Outcomes were feasibility, enrolment, data quality, and cost. RESULTS: Five LIONs varied in size from two to eight hospitals. All 24 hospitals we approached agreed to participate. The average monthly rate of enrolment at the research sites increased from 1.4 participants to 3.5 after expanding from a single institution model to the LION format (mean change = 2.1, range 0.9-3.7). Monthly performance improved over time. Data quality was similar for LIONs and non-LION sites, except for drug adherence which was lower at LIONs. The average cost to randomize and follow one participant during the study interval was 2.4 times the cost under the per-patient, cost-reimbursement strategy at non-LION sites. The cost ratio declined from 3.4 in year one to 1.8 in year two. LIMITATIONS: The LION strategy requires unprecedented collaboration and trust among institutions. Applicability beyond stroke requires confirmation. CONCLUSION: LIONs are a practical, reproducible method to increase enrolment in trial research. Twelve months were required for the average site to reach its potential. The per-participant cost at LIONs was higher than conventional sites but declined over time.

Family history of stroke and severity of neurologic deficit after stroke.

BACKGROUND: A family history of stroke is an independent risk factor for stroke. OBJECTIVE: To assess whether severity of neurologic deficit after stroke is associated with a family history of stroke. METHODS: The Ischemic Stroke Genetics Study, a five-center study of first-ever symptomatic ischemic stroke, assessed case subjects prospectively for a family history of stroke-affected first-degree relatives. Certified adjudicators used the NIH Stroke Scale (NIHSS) to determine the severity of neurologic deficit. RESULTS: A total of 505 case subjects were enrolled (median age, 65 years; 55% male), with 81% enrolled within 1 week of onset of symptoms. A sibling history of stroke was associated with more severe stroke. The odds of an NIHSS score of 5 or higher were 2.0 times greater for cases with a sibling history of stroke compared with cases with no sibling history (95% CI, 1.0 to 3.9). An association of family history of stroke in parents or children with stroke severity was not detected. CONCLUSIONS: A sibling history of stroke increased the likelihood of a more severe stroke in the case subjects, independent of age, sex, and other potential confounding factors. Other family history characteristics were not associated with stroke severity.

Vascular risk factors in cocaine users with stroke.

OBJECTIVES: To determine if the classic stroke risk factors, chronic hypertension, diabetes, cigarette smoking, chronic alcohol abuse, older age, and male sex, are also risk factors in cocaine-related ischemic and hemorrhagic stroke. METHODS: A computer search of ICD-9 codes identified 100 patients admitted to two inner city hospitals between 1986 and 1995 with acute ischemic or hemorrhagic stroke who also tested positive for cocaine in the urine. The case records of these patients were reviewed retrospectively. The ischemic and hemorrhagic stroke groups were compared with a control group of 109 cocaine users without a history of stroke. Multiple logistic regression was performed to see if the classic stroke risk factors independently increased the risk of cocaine-induced ischemic and/or hemorrhagic stroke. RESULTS: A total of 66 stroke patients in the study group had ischemic stroke, whereas 34 had hemorrhagic stroke. The stroke and control groups were similar in racial and gender composition. The mean ages of patients with ischemic and hemorrhagic stroke (both 41 years) were greater than the control group (34 years) (P<.01). Only chronic hypertension (odds ratio [OR] 5.2, P<.0001) and older age (OR 1.08/year increase of age, P<.0006) were independent risk factors for ischemic stroke. Female sex (OR 3.2, P<.015) and older age (OR 1.1/year increase of age, P<.0002) were independent risk factors for hemorrhagic stroke. CONCLUSIONS: Chronic hypertension and older age may magnify the risk of cocaine-related ischemic stroke, whereas female sex and older age may increase the risk of cocaine-related hemorrhagic stroke.

The Warfarin-Aspirin Symptomatic Intracranial Disease Study.

We conducted a retrospective, multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events (ischemic stroke, myocardial infarction, or sudden death) in patients with symptomatic stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991. Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study. Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups, yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate, 7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine stimulates cAMP-mediated taurine release from LRM55 glial cells.

The possible role of adenosine as a modulator or transmitter in the central nervous system was tested by measuring its effects on LRM55 astroglial cells. Two related cellular responses were measured--receptor activated increases in intracellular cAMP and cAMP-mediated taurine release. Taurine is a neuroinhibitory amino acid that is taken up, stored, and released from primary cultures of astrocytes and astroglial cells. Three-minute incubations of cells with adenosine caused a dose-dependent accumulation of intracellular cAMP and release of the taurine (EC50 = 5.0 x 10(-5) M and 1.6 x 10(-6) M, respectively). That the cellular responses were mediated through the activation of specific adenosine receptors was indicated by the observations that the adenosine receptor antagonist isobutylmethylxanthine (IBMX) but not the beta-adrenergic receptor antagonist 1-propranolol inhibited responses to adenosine. The study of various adenosine analogs showed a rank order of potency (chloroadenosine = 5'-(N-ethyl)carboxamido-adenosine greater than N6-(L-2-phenylisopropyl)-adenosine greater than cyclohexyladenosine = cyclopentyladenosine) characteristic of the low affinity A2-type adenosine receptors that have been associated with cAMP elevation in several tissues. These results indicate that, in addition to directly affecting neurons, adenosine may have a primary site of action on astroglial cells resulting in taurine release and subsequent inhibition of neuronal activity.