Cognitive impairment after acute encephalitis: an ERP study.

Cognitive deficits are often observed during the acute stage of encephalitis. It is presumed, that they persist and influence the long-term outcome, but data are very limited. Forty-seven patients with a definite or highly probable diagnosis of acute encephalitis were identified through retrospective analysis and prospectively followed up 6-84 months after the acute illness. P3 was carried out by oddball auditory paradigm, and P3 latency was measured as a marker of cognitive impairment. Healthy people, who matched the patients in age, were used as controls (n = 39). Statistical group analysis revealed no significant difference of the P3 latency between the patient and the control group. However a subgroup analysis showed significant longer P3 latencies in patients with a more unfavorable functional outcome at the time of follow-up. Patients with Herpes simplex virus (HSV) encephalitis had also more often abnormal P3 values compared to other etiologic subgroups, potentially indicating a higher percentage of patients with unfavorable cognitive outcome in this subgroup.

Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933].

BACKGROUND: The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. DESIGN: GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. CONCLUSION: 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. TRIAL REGISTRATION: Current Controlled TrialsISRCTN45122933.

HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment.

The modern antiretroviral treatment of human immunodeficiency virus (HIV-1) infection has considerably lowered the incidence of opportunistic infections. With the exception of the most severe dementia manifestations, the incidence and prevalence of HIV-associated neurocognitive disorders (HAND) have not decreased, and HAND continues to be relevant in daily clinical practice. Now, HAND occurs in earlier stages of HIV infection, and the clinical course differs from that before the widespread use of combination antiretroviral treatment (cART). The predominant clinical feature is a subcortical dementia with deficits in the domains concentration, attention, and memory. Motor signs such as gait disturbance and impaired manual dexterity have become less prominent. Prior to the advent of cART, the cerebral dysfunction could at least partially be explained by the viral load and by virus-associated histopathological findings. In subjects where cART has led to undetectable or at least very low viral load, the pathogenic virus-brain interaction is less direct, and an array of poorly understood immunological and probably toxic phenomena are discussed. This paper gives an overview of the current concepts in the field of HAND and provides suggestions for the diagnostic and therapeutic management.

A "malignant" variant of status epilepticus.

BACKGROUND: Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined the term malignant SE for this most severe variant of SE. OBJECTIVE: To assess frequency, risk factors, and in-hospital outcome of malignant SE. DESIGN: Retrospective cohort study. SETTING: Neurologic intensive care unit of a large university hospital. Patients Sample of 35 episodes of SE not responding to first-line anticonvulsants in 34 patients. MAIN OUTCOME MEASURES: Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases with refractory SE and persistent epileptic activity after failure of first-line anticonvulsants. RESULTS: Status epilepticus that could not be controlled by first-line anticonvulsants resulted in malignant SE in 20% of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P = .03). Encephalitis was identified as an independent risk factor for malignant SE (P = .008). Outcome in malignant SE was poor, with significantly longer duration of seizure activity (P<.001), longer stay in the neurologic intensive care unit (P<.001) and in the hospital (P = .007), and more patients with functional dependency at discharge from the hospital (P = .04). CONCLUSIONS: Malignant SE is not rare after failure of first-line anticonvulsants. The patient at risk is typically young and suffers from encephalitis. Such patients should be treated aggressively early in the course of SE to prevent malignant SE.

Functional, cognitive and emotional long-term outcome of patients with ischemic stroke requiring mechanical ventilation.

Prognosis of patients with ischemic stroke requiring mechanical ventilation (MV) has been reported to be poor. However, longterm survival and functional outcome have scarcely been studied and nothing is known about the prevalence of cognitive impairment or depression in survivors and their quality of life (QoL). We identified all patients treated for acute ischemic stroke on a Neurological Intensive Care Unit during 3.5 years who required MV for more than 24 hours. Early mortality rate at 2 months and survival rates at 1 and 2 years were determined. Survivors were examined for functional outcome (modified Rankin Scale (mRS), Barthel Index), cognitive impairment (Mini Mental State Examination (MMSE)), depression (Beck Depression Inventory, BDI) and QoL (Short Form-36). Clinical characteristics on admission were analyzed for prognostic significance. Of 101 consecutive patients, 44% died within 60 days. Survival rates at 1 and 2 years were 40% and 33%, respectively. Age > 60 years (p = 0.002) and Glasgow Coma Scale score < 10 on admission (p = 0.002) were independent predictors of early and late mortality. History of myocardial infarction (p = 0.007) independently predicted late mortality at 2 years. Of 33 surviving patients, nine (27%) had a good functional outcome (mRS 0-2). Of 27 survivors who could be interviewed, 17 (63%) had no cognitive impairment (MMSE > 24) and 20 (74%) did not suffer from relevant depression (BDI < 19). In conclusion, longer-term survival of patients with ischemic stroke requiring MV was 33% and every fourth survivor resumed an independent life without dementia or depression. Older patients comatose on admission and with concomitant cardiovascular disease had the lowest probability of a favorable outcome.

Timing the valve replacement in infective endocarditis involving the brain.

Neurological complications are very frequent in patients with infective endocarditis (20-40 %). In these patients it is unclear at what time a valve replacement should be performed. In order to develop a data based recommendation we studied 12 patients of our own and analyzed 228 patients from the literature. We included patients with valve replacement after a neurological complication of endocarditis and documented the time between manifestation and operation and the outcome. Based on these 240 patients we calculated the risk of neurological deterioration after the valve replacement. After brain infarction this risk is 20% within three days, 20-50% between day 4 and 14, but declines to < 10% after 14 days and < 1% after 4 weeks. Valve replacement within the first four weeks after intracranial hemorrhage has been reported to be successful only in individual cases. The risk of deteriorating declines later to 15%. Based on these limited data we suggest that valve replacement in patients with brain infarction should be considered within the first 72 hours if they have severe heart failure, otherwise after four weeks. Only a few selected patients with intracranial hemorrhage and progressive heart failure might benefit from valve replacement within the first four weeks. For all other neurological complications there are no reliable data. We propose a structured approach depending on cardiac and neurological complications and the time course of the disease.

Delayed occlusion after internal carotid artery dissection under heparin.

Internal carotid artery dissection (ICAD) is a frequent etiology of stroke in the young. Immediate anticoagulation with unfractionated heparin is the most frequent treatment. A theoretical side effect of unfractionated heparin is an increase in the intramural hematoma resulting in hemodynamic cerebral infarction. We studied 20 patients with ICAD. All patients were immediately treated with unfractionated heparin. Activated partial thromboplastin time (aPTT) ratios were measured twice daily. We prospectively monitored the course of ICAD with repeated ultrasound in hospital. Unexpectedly, delayed ICA occlusion was noted in 5 patients under treatment. One of these developed a watershed infarct. We then analyzed the aPTT ratios over the first 6 days after diagnosis. Patients with delayed occlusion had significantly higher aPTT ratios (2.6 +/- 0.4 vs. 2.0 +/- 0.5, p < 0.05). Within the limits of a partially retrospective design, our study seems to support the notion that unfractionated heparin can increase the intramural hematoma. Our findings further justify a randomized clinical trial to resolve the anticoagulant/antiplatelet debate.