Huang Y, Potter R, Sigurdson W
… +9 more, Kasten T, Connors R, Morris JC, Benzinger T, Mintun M, Ashwood T, Ferm M, Budd SL, Bateman RJ
Arch Neurol
· 2012 Dec · PMID 23229043
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OBJECTIVES: To investigate dynamic changes in human plasma β-amyloid (Aβ) concentrations, evaluate the effects of aging and amyloidosis on these dynamics, and determine their correlation with cerebrospinal fluid (CSF) Aβ...OBJECTIVES: To investigate dynamic changes in human plasma β-amyloid (Aβ) concentrations, evaluate the effects of aging and amyloidosis on these dynamics, and determine their correlation with cerebrospinal fluid (CSF) Aβ concentrations. DESIGN: A repeated plasma and CSF sampling study. SETTING: The Washington University School of Medicine in St Louis, Missouri. PARTICIPANTS: Older adults with amyloid deposition (Amyloid+), age-matched controls without amyloid deposition (Amyloid-), and younger normal controls (YNCs) were enrolled for the study. MAIN OUTCOME MEASURES: Hourly measurements of plasma Aβ were compared between groups by age and amyloidosis. Plasma Aβ and CSF Aβ concentrations were compared for correlation, linear increase, and circadian patterns. RESULTS: Circadian patterns were observed in plasma Aβ, with diminished amplitudes with aging. Linear increase of Aβ was only observed for CSF Aβ in the YNC and Amyloid- groups, but not in the Amyloid+ group. No linear increase was observed for plasma Aβ. No significant correlations were found between plasma and CSF Aβ concentrations. CONCLUSIONS: Plasma Aβ, like CSF, demonstrates a circadian pattern that is reduced in amplitude with increasing age but is unaffected by amyloid deposition. However, we found no evidence that plasma and CSF Aβ concentrations were related on an hourly or individual basis.
Paterson RW, Torres-Chae CC, Kuo AL
… +9 more, Ando T, Nguyen EA, Wong K, DeArmond SJ, Haman A, Garcia P, Johnson DY, Miller BL, Geschwind MD
Arch Neurol
· 2012 Dec · PMID 23229042
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OBJECTIVES: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct d...OBJECTIVES: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. DESIGN: Retrospective medical record review. SETTING: A specialty referral center of a tertiary academic medical center. PARTICIPANTS: One hundred sixty-three serial patients over a 5.5-year period who ultimately had pathologically proven sCJD. The study used the subset of 97 patients for whom we had adequate medical records. MAIN OUTCOME MEASURES: Other diagnoses considered in the differential diagnosis and types of medical specialties assessing patients with sCJD. RESULTS: Ninety-seven subjects' records were used in the final analysis. The most common disease categories of misdiagnosis were neurodegenerative, autoimmune/paraneoplastic, infectious, and toxic/metabolic disorders. The most common individual misdiagnoses were viral encephalitis, paraneoplastic disorder, depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy. The physicians who most commonly made these misdiagnoses were primary care physicians and neurologists; in the 18% of patients who were diagnosed correctly at their first assessment, the diagnosis was almost always by a neurologist. The mean time from onset to diagnosis was 7.9 months, an average of two-thirds of the way through their disease course. CONCLUSIONS: Diagnosis of sCJD is quite delayed. When evaluating patients with rapidly progressive dementia with suspected neurodegenerative, autoimmune, infectious, or toxic/metabolic etiology, sCJD should also be included in the differential diagnosis, and appropriate diagnostic tests, such as diffusion brain magnetic resonance imaging, should be considered. Primary care physicians and neurologists need improved training in sCJD diagnosis.
A 54-year-old white man presented with slowly progressive incoordination and weakness. He had normal motor development until, at 16 years of age, he noted difficulty walking and difficulty reading despite normal visual a...A 54-year-old white man presented with slowly progressive incoordination and weakness. He had normal motor development until, at 16 years of age, he noted difficulty walking and difficulty reading despite normal visual acuity. By the fourth decade of life, he developed poor coordination and balance, as well as inability to walk. In subsequent years, he developed progressive, painless sensory loss, weakness, and atrophy in his distal arms and legs. His vision problems progressed and he also developed dysarthria without dysphagia. Family history was negative except for an uncle who was described as "clumsy." Results of an oculomotor examination were notable for increased square-wave jerks, persistent bilateral gaze-evoked nystagmus with saccadic pursuit, intact vestibulo-ocular reflex, and saccadic dysmetria. He had a mixed dysarthria with flaccid and ataxic characteristics and severe weakness and atrophy in the distal limb muscles. Sensation was diminished to the midforearms and midthighs in all modalities. Deep tendon reflexes were absent throughout, with no response to plantar stimulation. He had marked appendicular ataxia with mild axial ataxia. Magnetic resonance imaging of the brain revealed severe cerebellar atrophy. Results of an electrodiagnostic study suggested a severe axonal sensorimotor polyneuropathy with active and chronic denervation. The differential diagnosis in a patient with ataxia, neuropathy, and oculomotor features is discussed; a methodical approach to the diagnostic workup is suggested; and the final diagnosis is revealed.
CONTEXT: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some...CONTEXT: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. OBJECTIVE: To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. MAIN OUTCOME MEASURES: Risk of stroke. RESULTS: The cohort comprised 39 398 men (47.2%) and 44 115 women (52.8%). At admission, women were older and had a higher CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS2 score, and warfarin treatment. CONCLUSION: Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.
BACKGROUND: Previous studies have not distinguished patients with acute cervical internal carotid artery (ICA) occlusions from those with intracranial occlusions and often consider them together in the same cohort. OBJEC...BACKGROUND: Previous studies have not distinguished patients with acute cervical internal carotid artery (ICA) occlusions from those with intracranial occlusions and often consider them together in the same cohort. OBJECTIVES: To evaluate the outcomes of patients with stroke from acute cervical ICA occlusion treated with intravenous thrombolysis or primary endovascular procedures and to identify early predictors of functional recovery among these patients. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: We studied patients with ischemic stroke who received intravenous thrombolysis or endovascular treatment for acute cervical ICA occlusion at St Mary's Hospital, Mayo Clinic, Rochester, Minnesota. We evaluated the associations of vascular risk factors, severity of stroke, arterial recanalization, presence of tandem occlusions, and collateral distal flow with functional recovery at 90 days after stroke. MAIN OUTCOME MEASURES: Favorable functional recovery (Modified Rankin Scale score, 0-2). RESULTS: We identified 21 patients (median age, 67 years; median National Institutes of Health Stroke Scale score at presentation, 13), of whom 13 patients received intravenous thrombolysis and 8 patients underwent primary endovascular treatment. Three patients who received intravenous thrombolysis underwent rescue endovascular treatment. Favorable functional recovery (Modified Rankin Scale score, 0-2) was observed in 7 patients who received intravenous thrombolysis and in 1 patient who underwent primary endovascular treatment. Good collateral distal flow and intracranial tandem occlusions were observed in 6 patients and 12 patients, respectively. Good collateral distal flow, observed more frequently in cigarette smokers, was associated with favorable functional recovery (odds ratio, 20; 95% CI, 2-242; P = .02). CONCLUSIONS: Intravenous thrombolysis should be administered as first-line treatment in patients with early acute cervical ICA occlusion. Treatment benefits are accentuated in patients with better collateral circulation.