Neurologic complications of pancreas and small bowel transplantation.

In the past decade, substantial improvements in patient and graft survival for pancreas and small bowel transplants have been achieved. Despite this progress, many patients still develop neurologic complications in the course of their illness. Small bowel transplants produce more neurologic complications because of the complex metabolic environment in which the procedure is performed and because of the intense immune suppression necessitated by the greater immunogenicity of the intestinal mucosa. Pancreas transplants stabilize and/or improve the signs and symptoms of diabetic neuropathy over time. Because transplantation of the pancreas is often coupled with a kidney transplant and small intestine with liver, neurologic complications in these patients sometimes reflect problems involving the organ partner or both organs. The spectrum of neurologic complications for pancreas and small bowel transplant recipients is similar to other organ transplants but their frequency varies depending on the type of transplant performed.

Metabolic and perfusion responses to recurrent peri-infarct depolarization during focal ischemia in the Spontaneously Hypertensive Rat: dominant contribution of sporadic CBF decrements to infarct expansion.

Peri-infarct depolarizations (PIDs) contribute to the evolution of focal ischemic lesions. Proposed mechanisms include both increased metabolic demand under conditions of attenuated perfusion and overt vasoconstrictive responses to depolarization. The present studies investigated the relative contributions of metabolic and perfusion effects to PID-associated infarct expansion during middle cerebral artery (MCA) occlusion in the Spontaneously Hypertensive Rat. The initial distribution of ischemic depolarization (ID) was established within minutes after MCA occlusion at a cerebral blood flow threshold of ∼40 mL/100 g per minute, with expansion of the depolarized territory during 3 hours detected in half of the animals. Peri-infarct depolarizations were associated with transient metabolic responses, comparable to those observed after spreading depression, with no evidence of cumulative energy failure after multiple transient depolarizations during 1 hour. Speckle contrast imaging of PID-associated flow transients documented prominent distal hyperemic flow responses that became progressively attenuated in regions of already impaired perfusion, with modest propagated flow decreases more proximal to the ischemic core. However, sporadic PIDs were associated with persistent decrements in perfusion, increasing tissue volume below the threshold for energy failure, ID and infarction. These latter, comparatively rare, events can account for the pattern of stepwise infarct expansion in this model.

Processes of care associated with acute stroke outcomes.

BACKGROUND: Many processes of care have been proposed as metrics to evaluate stroke care. We sought to identify processes of stroke care that are associated with improved patient outcomes after adjustment for both patient characteristics and other process measures. METHODS: This retrospective cohort study included patients 18 years or older with an ischemic stroke or transient ischemic attack (TIA) onset no more than 2 days before admission and a neurologic deficit on admission. Patients were excluded if they resided in a skilled nursing facility, were already admitted to the hospital at stroke onset, or were transferred from another acute-care facility. The combined outcome included in-hospital mortality, discharge to hospice, or discharge to a skilled nursing facility. Seven processes of stroke care were evaluated: fever management, hypoxia management, blood pressure management, neurologic evaluation, swallowing evaluation, deep vein thrombosis (DVT) prophylaxis, and early mobilization. Risk adjustment included age, comorbidity (medical history), concomitant medical illness present at admission, preadmission symptom course, prestroke functional status, code status, stroke severity, nonneurologic status, modified APACHE (Acute Physiology and Chronic Health Evaluation) III score, and admission brain imaging findings. RESULTS: Among 1487 patients, the outcome was observed in 239 (16%). Three processes of care were independently associated with an improvement in the outcome after adjustment: swallowing evaluation (adjusted odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43-0.94); DVT prophylaxis (adjusted OR, 0.60; 95% CI, 0.37-0.96); and treating all episodes of hypoxia with supplemental oxygen (adjusted OR, 0.26; 95% CI, 0.09-0.73). CONCLUSION: Outcomes among patients with ischemic stroke or TIA can be improved by attention to swallowing function, DVT prophylaxis, and treatment of hypoxia.

Cerebral blood flow thresholds for mRNA synthesis after focal ischemia and the effect of MK-801.

BACKGROUND AND PURPOSE: MK-801 is a noncompetitive antagonist of N-methyl-d-aspartate subtype glutamate receptors with protective efficacy in experimental stroke. This study examined the impact of MK-801 on cerebral blood flow (CBF) and its relationship to gene expression changes during focal ischemia. METHODS: Spontaneously hypertensive rats were subjected to surgical occlusion of the middle cerebral artery and ipsilateral common carotid artery after 30 minutes pretreatment with 5 mg/kg MK-801 or saline vehicle. After 2.5 hours of ischemia, regional CBF was evaluated by [14C]iodoantipyrine autoradiography and compared with distributions of gene expression changes evaluated by in situ hybridization detection of mRNAs encoding several immediate-early genes and the stress protein, hsp72. RESULTS: MK-801 increased CBF in contralateral cortex from 93+/-15 to 187+/-37 mL/100 g per minute and produced a significant 25% reduction in the volume of ischemic cortex ipsilateral to occlusion. The extent of cortex failing to express inducible mRNAs correspondingly decreased, but the CBF threshold for mRNA synthesis remained unchanged (25 to 30 mL/100 g per minute). Widespread immediate-early gene expression in the neocortex became restricted to periinfarct regions after MK-801 treatment, and hybridization patterns in the striatum and hippocampus reflected the altered topography of cortical activation after drug treatment. CONCLUSIONS: MK-801 alters ischemia-induced gene expression by 2 distinct mechanisms. Generalized increases in CBF reduce the volume of cortex falling below ischemic injury thresholds, protecting tissue and facilitating transcription of inducible genes proximal to the ischemic focus. In addition, MK-801 attenuates the signals that induce expression of immediate-early genes in cortical and subcortical regions remote from the middle cerebral artery territory.

Anticardiolipin antibody in vascular parkinsonism.

Vascular parkinsonism (VP) is characterized by predominantly lower body involvement with gait impairment and postural instability, often without tremor, and by relative levodopa unresponsiveness. Neuroimaging studies demonstrate multiple infarcts or ischemic changes in periventricular white matter. Anticardiolipin antibodies (ACLA) are associated with hypercoagulable states and increased stroke risk. Review of our Movement Disorders Clinic records identified 44 individuals with a diagnosis of VP. ACLA have been obtained in 22 of these patients (mean age, 78.3 years; mean Mini-Mental Status Exam score, 25.8). Gait disturbance was the initial clinical feature in 82% of the patients, and levodopa responsiveness was present in 18% of those treated. In 9 of the 22 (40.9%), ACLA immunoglobulin G was positive. No significant differences in clinical features or risk factors (hypertension, diabetes, coronary artery disease, and clinical stroke) were evident between ACLA+ and ACLA- groups. Since the presence of ACLA in individuals with stroke is usually treated by full-scale anticoagulation with warfarin, our findings raise the question whether such treatment should also be used in persons with VP who are ACLA positive.