The problem of ignoring interconnectedness in genetic research.
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Clinical Protocols↗
Biomedical subjects
J F Meschia
Publications and source records attributed to J F Meschia.
Verifying the stroke-free phenotype by structured telephone interview.
BACKGROUND AND PURPOSE: Case-control, cohort, and twin studies support a genetic contribution to ischemic stroke risk. Sibling pair linkage methods require identification of concordant or discordant siblings or both. We designed and tested a structured telephone interview to verify the stroke-free phenotype. METHODS: A coordinator unaware of medical record data used an 8-item questionnaire to conduct a structured telephone interview of 70 outpatients aged >60 years. The questionnaire inquired about the sudden onset of deficits in strength, sensation, vision, and language. A subject was defined as stroke free by interview if responses to all items on the questionnaire were negative. Results of the telephone interview were compared with data obtained from a systematic medical record review (benchmark). RESULTS: Interview time was 5 minutes or less for all subjects. All subjects who began the interview completed it. Records were reviewed in all subjects. Medical record review detected ischemic stroke or transient ischemic attack (TIA), or both, in 5 patients (7%). There were no significant differences in sex distribution or risk factor rates in patients who were designated stroke free or not stroke free by interview. Having 1 or more positive items on the questionnaire was significantly associated with finding stroke (P<0.001), TIA (P<0.001), or either stroke or TIA (P<0.001), on medical record review. The telephone interview had a sensitivity of 1.0 (95% CI 0.48 to 1.0), specificity of 0.86 (95% CI 0.75 to 0.93), positive predictive value of 0.36 (95% CI 0.13 to 0.65), and negative predictive value of 1.0 (95% CI 0.94 to 1.0). CONCLUSIONS: Our instrument can identify the stroke-free individual with a high degree of confidence in a very efficient manner. It may be particularly suited for centralized verification of stroke discordancy in multicentered sib-pair genetic studies.
Aged↗
Cerebral embolization presenting as delayed, severe obtundation in the postanesthesia care unit after total hip arthroplasty.
Catastrophic neurologic events occur rarely postoperatively and must be diagnosed quickly. A 63-year-old woman who had undergone uneventful total hip arthroplasty experienced obtundation after admission to the postanesthesia care unit. Cranial magnetic resonance imaging revealed multiple lesions consistent with ischemia or infarction, and fat cerebral embolism was diagnosed. We describe the numerous complications that may occur in patients in the postanesthesia care unit and review the differential diagnosis of altered mental status in such patients. Paradoxical cerebral fat embolization must be considered in the differential diagnosis of altered mental status after pelvic or long bone fracture or lower extremity major joint replacement, and this condition may occur despite normal pulmonary function and no patent foramen ovale or right-to-left intracardiac shunt. Magnetic resonance imaging with T2-weighted sequences is the cranial imaging study of choice for early evaluation of patients with sudden multifocal neurologic deficits and suspected fat embolism syndrome.
Anesthesia Recovery Period↗
Distinguishing primary angiitis of the central nervous system from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: the importance of family history.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically linked neurologic disease characterized by recurrent strokes and progressive or stepwise dementia, with or without migraine-like headaches, seizures, and pseudobulbar palsy. We describe a patient referred with a diagnosis of treatment-refractory primary angiitis of the central nervous system. Meningocortical and skin biopsies confirmed that the patient had CADASIL. Clinical and radiographic differences in these disorders may be subtle, but awareness of them is crucial if the patient is to avoid unnecessary exposure to potentially deleterious immunosuppressive therapy.
Dementia, Multi-Infarct↗
Thalamic hemorrhage following carotid endarterectomy-induced labile blood pressure: controlling the liability with clonidine--a case report.
Carotid endarterectomy can lead to alterations in baroreceptor sensitivity. Impairment of this sensitivity can in turn lead to volatility of blood pressure (baroreflex failure syndrome--BFS). Rapid elevations in blood pressure can cause hypertensive encephalopathy in a patient with BFS. A patient is presented with hypertensive intracerebral hemorrhage associated with BFS.
Aged↗
Reversible segmental cerebral arterial vasospasm and cerebral infarction: possible association with excessive use of sumatriptan and Midrin.
OBJECTIVE: To describe a patient who developed reversible segmental cerebral arterial vasospasm and cerebral infarction while taking excessive amounts of sumatriptan succinate and a combination drug (Midrin) consisting of isometheptene mucate, 65 mg, dichloralphenazone, 100 mg, and acetaminophen, 325 mg. DESIGN: Case report. SETTING: Tertiary care center. PATIENT: A 43-year-old man who developed a left occipital infarct after taking a total of 23 sumatriptan succinate tablets (25 mg per tablet) and 32 Midrin tablets during a 7-day period and who on digital subtraction angiography was shown to have segmental cerebral arterial narrowing in multiple vessels. An extensive evaluation for other possible risk factors for cerebral infarction was unrevealing. MAIN OUTCOME AND RESULTS: Discontinuation of sumatriptan and Midrin regimens and administration of nicardipine hydrochloride led to nearly total resolution of the angiographic findings, and the patient had no recurrent strokes. CONCLUSIONS: One should consider the diagnosis of drug-induced vasospasm in patients with cerebral infarction and a history of excessive use of sumatriptan and Midrin. The initial angiographic abnormalities may resemble those found in patients with primary angiitis of the central nervous system.
Acetaminophen↗
Is hormone replacement a risk factor for ischemic stroke in women with factor V Leiden mutation?
OBJECTIVE: To describe a patient with multifocal cerebral ischemia whose only identified potential risk factors were use of postmenopausal hormone replacement and heterozygosity to factor V Leiden mutation. DESIGN: A case report. SETTING: A tertiary care center. PATIENT: A 51-year-old woman taking hormone replacement (0.625 mg/d of estrogen alternating with 10 mg/d of medroxyprogesterone) presented with a generalized tonic-clonic seizure. She had persistent multifocal non-enhancing lesions on magnetic resonance imaging of the brain. A stereotactic biopsy of the brain performed to exclude gliomatosis cerebri was consistent with cerebral ischemia. An extensive evaluation to uncover the cause of stroke revealed only heterozygosity to factor V Leiden mutation. MAIN OUTCOME AND RESULTS: Hormonal replacement was discontinued and the patient had no recurrent ischemic strokes. CONCLUSIONS: Postmenopausal hormonal replacement may be a risk factor for ischemic stroke in women with the factor V Leiden mutation. Ongoing trials of hormonal replacement provide an opportunity to test this hypothesis.
Brain Ischemia↗
49-year-old woman with back pain and loss of consciousness.
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Adult↗
Anticoagulant and defibrinogenating agents in acute ischemic stroke and cerebral venous thrombosis.
Anticoagulants have been used in patients with acute ischemic stroke to limit infarct volume and to prevent reinfarction and thrombotic complications like deep venous thrombosis. Three important randomized trials of anticoagulants have been reported recently. One trial showed that nadroparin reduced the percentage of patients with poor outcome at 6 months. One unblinded trial of subcutaneous unfractionated heparin showed that heparin reduced the rate of early recurrent stroke, but this benefit was offset by an increase in hemorrhages. A trial of the heparinoid ORG 10172 showed no efficacy overall at 3 months, although there was an increase in patients with very favorable outcomes at 7 days. The defibrinogenating agent ancrod has shown promise in a series of small clinical trials, but efficacy has not been established. There are no reliable data on the use of antithrombotic agents to prevent reocclusion after thrombolytic therapy. Anticoagulants are generally recommended in patients with cerebral venous thrombosis, but the recommendation is supported by only one small and methodologically limited trial.
Ancrod↗
Simultaneous bilateral thalamic hemorrhages following the administration of intravenous tissue plasminogen activator.
A patient suffered the onset of simultaneous bilateral thalamic hemorrhage several hours after the administration of intravenous tissue plasminogen activator. The patient exhibited features of the paramedian diencephalic syndrome, including executive dysfunction, anterograde amnesia, inattention, and disturbances of visual perception. During rehabilitation, she made significant gains in overlearned activities of daily living tasks, but her inability to retain new information left her severely disabled. The use of intravenous thrombolytic therapy is believed to account for this patient's unusual stroke syndrome. With recent evidence supporting the efficacy of intravenous thrombolysis in acute stroke, patients with multiple hemorrhagic strokes as a result of thrombolysis may become more common on rehabilitation services.
Aged↗
Mechanical ventilation.
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Cerebrovascular Disorders↗
Manipulation of coagulation factors in acute stroke.
In patients with an acute cerebral infarction, anticoagulation may spare tissue in the ischaemic penumbra from irreversible necrosis by preventing thrombus extension from a vascular bed with good collateral circulation to one with poor collateral circulation. In addition to the possibility of limiting infarct volume, anticoagulation may be given acutely to prevent early recurrent cerebral infarction or to prevent or treat thrombus outside the nervous system (i.e. deep venous thrombosis or pulmonary embolus). In one controlled trial of a low molecular weight heparin, administration of nadroparin calcium within 48 hours of onset of cerebral infarction decreased the combined incidence of dependency and all-cause mortality at 6 months. Another controlled trial in patients with cerebral venous thrombosis demonstrated the benefit of continuous intravenous adjusted-dose unfractionated (UF) heparin compared with placebo. Although results of anticoagulation appear promising in patients with acute cerebral infarction and cerebral venous thrombosis, the benefits of these agents remain unconfirmed. The results of large multicentre trials using a heparinoid (ORG 10172) and subcutaneous UF heparin in patients with acute cerebral infarction are expected within the year.
Acute Disease↗
Clostridium perfringens subdural empyema and meningitis.
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Clostridium Infections↗
Familial systematized epidermal nevus syndrome.
Epidermal nevi are typically congenital but rarely familial. We report on a family in which 3 relatives have systematized epidermal nevi. The propositus also has evidence of a hemangioma and a hemangioendothelioma. Peripheral blood and skin fibroblast karyotypes of the propositus did not show evidence of mosaicism. Epidermal nevi have been associated with nondermatologic pathology, involving the nervous, vascular, and skeletal systems in sporadic cases. This report demonstrates that nondermatologic pathology can be also be associated with systematized epidermal nevi in a familial setting. The apparent skipping of generations may be explained by autosomal dominant inheritance with decreased penetrance.
Abdominal Neoplasms↗
Secretion of the beta/A4 amyloid precursor protein. Identification of a cleavage site in cultured mammalian cells.
Alzheimer's disease, a progressive neurodegenerative disorder, affects greater than 10% of the population of individuals greater than 65 years of age. A principal neuropathological feature of this disease is the senile plaque, a fibrillar extracellular deposit primarily composed of a approximately 4-kDa peptide, beta/A4, derived from the amyloid precursor protein (APP). Studies in cultured cells have documented that APP matures through a constitutive secretory pathway and is cleaved at or near the cell surface to release a large ectodomain into the extracellular space. To define the APP cleavage site, we constructed a Chinese hamster ovary cell line, which constitutively overexpresses human APP-770, and analyzed the COOH termini of secreted APP-770-related molecules. Using plasma desorption mass spectrometry and chemical microsequencing, we document that an APP cleavage site in Chinese hamster ovary cells leading to secretion occurs immediately COOH-terminal to lysine residue 687, which lies adjacent to the hydrophobic membrane-spanning domain.
Amino Acid Sequence↗