An unusual stroke-like clinical presentation of Creutzfeldt-Jakob disease: acute vestibular syndrome

INTRODUCTION Vertigo and dizziness are common neurological symptoms in general practice. Most patients have benign peripheral vestibular disorders, but some have dangerous central causes. Recent research has shown that bedside oculomotor examinations accurately discriminate central from peripheral lesions in those with new, acute, continuous vertigo/dizziness with nausea/vomiting, gait unsteadiness, and nystagmus, known as the acute vestibular syndrome. CASE REPORT A 56-year-old man presented to the emergency department with acute vestibular syndrome for 1 week. The patient had no focal neurological symptoms or signs. The presence of direction-fixed, horizontal nystagmus suppressed by visual fixation without vertical ocular misalignment (skew deviation) was consistent with an acute peripheral vestibulopathy, but bilaterally normal vestibuloocular reflexes, confirmed by quantitative horizontal head impulse testing, strongly indicated a central localization. Because of a long delay in care, the patient left the emergency department without treatment. He returned 1 week later with progressive gait disturbance, limb ataxia, myoclonus, and new cognitive deficits. His subsequent course included a rapid neurological decline culminating in home hospice placement and death within 1 month. Magnetic resonance imaging revealed restricted diffusion involving the basal ganglia and cerebral cortex. Spinal fluid 14-3-3 protein was elevated. The rapidly progressive clinical course with dementia, ataxia, and myoclonus plus corroborative neuroimaging and spinal fluid findings confirmed a clinicoradiographic diagnosis of Creutzfeldt-Jacob disease. CONCLUSIONS To our knowledge, this is the first report of an initial presentation of Creutzfeldt-Jacob disease closely mimicking vestibular neuritis, expanding the known clinical spectrum of prion disease presentations. Despite the initial absence of neurological signs, the central lesion location was differentiated from a benign peripheral vestibulopathy at the first visit using simple bedside vestibular tests. Familiarity with these tests could help providers prevent initial misdiagnosis of important central disorders in patients presenting vertigo or dizziness.

Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in patients with SIRS and acute respiratory failure

Neuromuscular abnormalities are common in ICU patients. We aimed to assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its impact on outcome.

Effects of TLR agonists on the hypoxia-regulated transcription factor HIF-1alpha and dendritic cell maturation under normoxic conditions

Dendritic cells (DC) are professional antigen presenting cells that represent an important link between innate and adaptive immunity. Danger signals such as toll-like receptor (TLR) agonists induce maturation of DC leading to a T-cell mediated adaptive immune response. In this study, we show that exogenous as well as endogenous inflammatory stimuli for TLR4 and TLR2 induce the expression of HIF-1alpha in human monocyte-derived DC under normoxic conditions. On the functional level, inhibition of HIF-1alpha using chetomin (CTM), YC-1 and digoxin lead to no consistent effect on MoDC maturation, or cytokine secretion despite having the common effect of blocking HIF-1alpha stabilization or activity through different mechanisms. Stabilization of HIF-1alpha protein by hypoxia or CoCl(2) did not result in maturation of human DC. In addition, we could show that TLR stimulation resulted in an increase of HIF-1alpha controlled VEGF secretion. These results show that stimulation of human MoDC with exogenous as well as endogenous TLR agonists induces the expression of HIF-1alpha in a time-dependent manner. Hypoxia alone does not induce maturation of DC, but is able to augment maturation after TLR ligation. Current evidence suggests that different target genes may be affected by HIF-1alpha under normoxic conditions with physiological roles that differ from those induced by hypoxia.

Reversal of established lupus nephritis and prolonged survival of New Zealand black x New Zealand white mice treated with the topoisomerase I inhibitor irinotecan

Systemic lupus erythematosus is a chronic autoimmune disorder that predominantly affects women of childbearing age. Lupus-associated glomerulonephritis is a major cause of mortality in these patients. Current treatment protocols for systemic lupus erythematosus include cyclophosphamide, prednisolone, azathioprine, and mycophenolate mofetil. However, in mice none of these agents alone or in combination were shown to reverse established proteinuria. Using New Zealand Black x New Zealand White F1 mice, we report that administration of the topoisomerase I inhibitor irinotecan from week 13 completely prevented the onset of proteinuria and prolonged survival up to at least 90 wk without detectable side effects. Furthermore, application of irinotecan to mice with established lupus nephritis, as indicated by grade 3+ (> or =300 mg/dl) and grade 4+ (> or =2000 mg/dl) proteinuria and, according to a median age of 35 wk, resulted in remission rates of 75% and 55%, respectively. Survival was significantly prolonged with 73 wk (grade 3+ and 4+ combined) versus 40 wk for control animals. Although total IgG and anti-dsDNA Abs in the serum and mesangial IgG deposits in the kidneys were not reduced in irinotecan-treated mice, subendothelial immune deposits were considerably diminished, suggesting a prevention of glomerular basement membrane disruption. This effect was accompanied by increased rates of ssDNA breaks and inhibition of renal cell apoptosis being different to what is known about irinotecan in anticancer therapy. In conclusion, our data provide evidence that irinotecan might represent an entirely new strategy for the treatment of systemic lupus erythematosus.

Perioperative metabolic changes in patients undergoing cardiac surgery

Perioperative metabolic changes in cardiac surgical patients are not only induced by tissue injury and extracorporeal circulation per se: the systemic inflammatory response to surgical trauma and extracorporeal circulation, perioperative hypothermia, cardiovascular and neuroendocrine responses, and drugs and blood products used to maintain cardiovascular function and anesthesia contribute to varying degrees. The pathophysiologic changes include increased oxygen consumption and energy expenditure; increased secretion of adrenocorticotrophic hormone, cortisol, epinephrine, norepinephrine, insulin, and growth hormone; and decreased total tri-iodothyronine levels. Easily measurable metabolic consequences of these changes include hyperglycemia, hyperlactatemia, increased aspartate, glutamate and free fatty acid concentrations, hypokalemia, increased production of inflammatory cytokines, and increased consumption of complement and adhesion molecules. Nutritional risk before elective cardiac surgery-defined as preoperative unintended pathologic weight loss/low amount of food intake in the preceding week or low body mass index-is related to adverse postoperative outcome. Improvements in surgical techniques, anesthesia, and perioperative management have been designed to minimize the stressful stimulus to catabolism, thereby slowing the wasting process to the point where much less nutrition is required to meet metabolic requirements. Early nutrition in cardiac surgery is safe and well tolerated.

Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension

Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.