Dara G. Jamieson

Alzheimer's Disease with Prominent Visual Symptoms: Clinical and Metabolic Evaluation

The authors examined eight patients with dementia of the Alzheimers type (DAT), five with prominent visual symptoms early in the illness (VS) and three with no visual symptoms (NVS). Results of neuro-ophthalmologic examinations on VS patients showed relatively consistent abnormalities in figure copying, color vision tested by isochromatic plates, and stereopsis. Cerebral glucose metabolism determined by 18F-fluoro-2-deoxyglucose positron emission tomography (PET) was unchanged in primary visual cortex of VS and NVS patients compared with 12 normal volunteers of similar age and sex. Glucose metabolism in VS patients was decreased by 45 and 34% in left and right visual association cortex (P less than 0.01 and P less than 0.05, respectively) and 34 and 37% in left and right inferior parietal cortex (P less than 0.05) compared with controls; NVS patients had no significant metabolic alteration in these areas. Symptoms, physical examination, and metabolic imaging imply that these patients are a heterogenous but distinct clinical subgroup of DAT often with mild dementia who have visual symptoms due primarily to visual agnosia.

Atherosclerotic carotid artery disease in patients with retinal ischemic syndromes

The extracranial carotid systems of 105 patients with retinal ischemia were examined using B-mode ultrasonography with integrated pulsed Doppler. Sixty-four patients had amaurosis fugax (AF), 17 central retinal artery occlusions (CRAO), and 21 branch retinal artery occlusions (BRAO). The prevalence of carotid stenosis (≥60%) ipsilateral to the symptomatic eye was low (16%). Eighty-six percent of AF patients had either no plaque or plaque causing less than a 60% stenosis. A significant proportion of subjects with normal duplex scans had alternative explanations for their retinal ischemia (eg, migraine, cardiac embolus). Patients with Hollenhorst plaques were more likely to have stenotic or ulcerated plaque (p = 0.04). The degree of carotid stenosis correlated significantly with the number of vascular risk factors identified in individual patients (p = 0.02). The presence of risk factors was more common in CRAO and BRAO patients compared with the AF group. Combined ultrasound-Doppler investigations of the carotid bifurcation are valuable noninvasive tools for the screening of patients with retinal ischemia.

The safety of triptans in the treatment of patients with migraine

The introduction of the triptans (5-hydroxytryptophan [5-HT] (1B/1D) agonists) in the past decade has brought migraine-specific pain relief to those suffering from migraine. These drugs activate the serotonin receptors 5-HT(1B) and 5-HT(1D) on cerebral vessels. Concerns about their safety, particularly in patients with vascular risk factors, have been raised because triptans also activate the 5-HT(1B) receptors on coronary arteries. Although triptans are contraindicated in patients with cardiac or cerebrovascular disease, they are safer than many other medications used to treat patients with migraine, including the nonspecific serotonin-agonist ergot preparations.

Cerebral blood flow variations in CNS lupus

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.

Review of antiplatelet therapy in secondary prevention of cerebrovascular events: a need for direct comparisons between antiplatelet agents.

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents—aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal—have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ERDP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.

Gene expression of apolipoprotein(a) within the wall of human aorta and carotid arteries

Atherosclerosis is associated with arterial deposition of low density lipoprotein (LDL) and lipoprotein(a), Lp(a). Both lipoproteins have been detected in atherosclerotic vessels; however, while LDL has been shown to be only blood-derived, it is not clear whether Lp(a) is also produced within the vessel wall. In the present investigation we studied gene expression of apo(a) and apoB in human blood vessels. Aorta, carotid arteries and liver specimens from 29 adult and pediatric autopsy cases were studied by RT-PCR and Southern blot analysis with primers and probes specific for apo(a), apoB and GAPDH (a control housekeeping gene). The mRNA of apo(a), but not apoB, was found within the vessel wall in both adult atherosclerotic arterial vessels and in pediatric non atherosclerotic vessels. Neither apo(a) nor apoB mRNA was detected in femoral veins. To verify the nature of the detected transcripts, we cloned the 162 base pair (bp) RT-PCR product derived from the arterial wall total RNA. Nucleotide sequencing revealed 100% homology with the apo(a) gene. Thus, while LDL in atherosclerotic arteries is exclusively blood-derived, the accumulation of Lp(a) within the artery may be due in part to in situ production of apo(a) within the vessel wall.

Real-world experiences in migraine therapy with rizatriptan.

Objective.—To evaluate the effectiveness of rizatriptan for acute migraine treatment and patient satisfaction with the drug in usual clinical practice settings.

The Role of Neuroimaging in Headache

Headaches are a universal experience and one of the most common causes for physician consultation. The physician must determine whether a neuroimaging study is warranted to aid in the diagnosis of primary or secondary headaches. Guidelines on neuroimaging of headache patients have been developed based on review of the literature; however, their applicability must be adapted to specific clinical situations. In general, neuroimaging is most likely to be useful if the history is not typical of a primary headache type (eg, tension type, migraine, cluster headaches) or the neurological examination is abnormal. Neuroimaging has been crucial in the investigation of the pathogenesis of migraine and cluster headaches. Secondary headaches, which may be diagnosed by neuroimaging studies, include subarachnoid hemorrhage, cerebral venous thrombosis, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, aqueductal stenosis, and arterial dissection.

Positron emission tomography of the brain

Positron emission tomography (PET) is a technique of transverse tomographic imaging in which detection of two photons emitted from the annihilation of a positron and an electron is used to reconstruct the distribution of a positron emitting isotope within an object. PET provides the capacity to quantitatively measure the local tissue distribution of a variety of radionuclides that are attached to compounds that distribute according to function. Although this technique has been used to measure multiple functions and receptors within the brain, one of the most widespread uses is the measurement of local cerebral glucose metabolism based on the deoxyglucose method. In this article, the application of PET to clinical disorders such as dementia, brain tumors, psychiatric disease, epilepsy, movement disorders, and stroke as well as to normal states such as aging are examined.