Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.

[Rabies and Bornavirus encephalitis : Fatal emerging viral encephalitis-a potential problem for organ recipients]. / Tollwut und Bornavirus-Enzephalitis : Fatale "emerging" virale Enzephalitis ­ ein potenzielles Problem bei Organempfängern.

A severe, often fatal encephalitis needs to be extensively and carefully clarified, especially when it occurs in a patient weeks or months after an organ transplantation. If the donor was viremic at the time of the organ removal or living viruses were present in the organ tissue, many viruses can be transferred to the organ recipient. This has been repeatedly reported in recent years and decades. In this overview rabies is discussed as a particularly important form of viral encephalitis, which is transferred via organs and always has a fatal outcome, because patients carry a high risk of infection for all caregivers. Bornavirus has been known in veterinary medicine for many decades and in human medicine has been discussed as possibly being associated with psychiatric diseases. Very recently Bornavirus has been identified as the causative pathogen of fatal encephalitis in organ recipients. The aim of this article is to raise awareness for rabies and Bornavirus disease in intensive care medicine and neurology for organ donors and those taking care of organ recipients. Prevention by knowledge can be lifesaving.

Acyclovir resistance in herpes simplex virus type I encephalitis: a case report.

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Clusters of cortical spreading depolarizations in a patient with intracerebral hemorrhage: a multimodal neuromonitoring study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Cortical spreading depolarizations (CSDs) increase brain matrix metalloproteinase (MMP)-9 activity leading to perihematomal edema expansion in experimental ICH. METHODS: The purpose of this report is to describe cerebral metabolic changes and brain extracellular MMP-9 levels in a patient with CSDs and perihematomal edema expansion after ICH. RESULTS: We present a 66-year-old male patient with ICH who underwent craniotomy for hematoma evacuation. Multimodal neuromonitoring data of the perihematomal region revealed metabolic distress and increased MMP-9 levels in the brain extracellular fluid during perihematomal edema progression. At the same time, subdural electrocorticography showed clusters of CSDs, which disappeared after ketamine anesthesia on day six. Perihematomal edema regression was associated with decreasing cerebral MMP-9 levels. CONCLUSIONS: This novel association between clusters of CSDs, brain metabolic distress, and increased MMP-9 levels expands our knowledge about secondary brain injury after ICH. The role of ketamine after this devastating disorder needs further studies.

Nosocomial ventriculitis and meningitis in neurocritical care patients.

BACKGROUND: External ventricular drainage (EVD) is frequently necessary in neurological and neurosurgical intensive care patients. A major complication of this procedure is an EVD-related venticulitis or meningitis. The purpose of this review is (1) to address the magnitude of the problem in the neurocritical care patient population, (2) to discuss the difficulties in providing an appropriate and timely diagnosis of this disease entity and (3) to propose an algorithm for both rapid diagnosis and appropriate therapy. METHODS: A MEDLINE literature search was carried out for studies from January 1990 through March 2008 reporting on ventriculostomy, EVD-related central nervous system infections, in particular ventriculitis and meningitis. RESULTS: EVD-related ventriculitis is a serious nosocomial complication in the neurocritical care setting where EVD catheters are frequently used for the management of elevated ICP secondary to acute hydrocephalus primarily caused by subarachnoid and intraventricular hemorrhage or traumatic brain injury. Infection rate is high with reported incidences in the range of 5 % up to more than 20 %. Predisposing factors for infection are non-adherence to rigid insertion and maintenance protocols, leakage of cerebrospinal fluid (CSF), catheter irrigation and the frequency of EVD manipulation. Diagnosis is frequently impaired either by the presence of systemic inflammation due to the primary disease or because the hemorrhagic CSF itself may cause an inflammatory reaction. Furthermore, the most common pathogens involved in EVD-related infections, i. e., staphylococci, initially provoke only a mild inflammatory response in the CSF and therefore patients rarely present with clear-cut clinical signs indicating severe central nervous system infection, in particular, ventriculitis. CONCLUSION: Nosocomial EVD-related ventriculitis is a significant cause of morbidity and mortality in critically ill neurological patients. Rapid diagnosis and prompt initiation of appropriate antimicrobial therapy is needed. A stepwise algorithm for the management of EVD-related ventriculitis is proposed.

rFVIIa--for acute rebleeding of a cerebral cavernous malformation.

Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa.

Neurologic complications of sepsis.

Over the past decades, the incidence of sepsis and resultant neurologic sequelae has increased, both in industrialized and low- or middle-income countries, by approximately 5% per year. Up to 300 patients per 100 000 population per year are reported to suffer from sepsis, severe sepsis, and septic shock. Mortality is up to 30%, depending on the precision of diagnostic criteria. The increasing incidence of sepsis is partially explained by demographic changes in society, with aging, increasing numbers of immunocompromised patients, dissemination of multiresistant pathogens, and greater availability of supportive medical care in both industrialized and middle-income countries. This results in more septic patients being admitted to intensive care units. Septic encephalopathy is a manifestation especially of severe sepsis and septic shock where the neurologist plays a crucial role in diagnosis and management. It is well known that timely treatment of sepsis improves outcome and that septic encephalopathy may precede other signs and symptoms. Particularly in the elderly and immunocompromised patient, the brain may be the first organ to show signs of failure. The neurologist diagnosing early septic encephalopathy may therefore contribute to the optimal management of septic patients. The brain is not only an organ failing in sepsis (a "sepsis victim" - as with other organs), but it also overwhelmingly influences all inflammatory processes on a variety of pathophysiologic levels, thus contributing to the initiation and propagation of septic processes. Therefore, the best possible pathophysiologic understanding of septic encephalopathy is essential for its management, and the earliest possible therapy is crucial to prevent the evolution of septic encephalopathy, brain failure, and poor prognosis.

Behavioral characterization of the anterior injection model of subarachnoid hemorrhage.

BACKGROUND: The applicability of various neurological scores has not been sufficiently characterized in the anterior injection model of subarachnoid hemorrhage (SAH). Therefore this study was performed to evaluate different behavioral tests for quantifying disease severity. METHODS: Different volumes of autologous blood were injected stereotaxically into the prechiasmatic cistern of mice. Sham controls underwent the same procedure without blood injection. The following seven days after surgery, mice were evaluated for behavioral deficits by the SHIRPA score, beam balance and flex field analyses. Brains were further processed for histological analyses. RESULTS: Flex field analysis of SAH animals showed a significant reduction of locomotor activity compared to controls in the first two days after SAH. This reduction was more intense in animals with a higher amount of injected blood. The SHIRPA score revealed a significant reduction in motor behavior in SAH animals two days after surgery. A significant increase of GFAP expression, Fluoro Jade C and TUNEL positive cells as well as microthrombi was observed in SAH animals compared to sham controls in the early phase of SAH. There was a significant negative correlation between flex field righting and the number of degenerative neurons or microthrombi in the first two days after SAH. CONCLUSION: The results of flex field analysis and SHIRPA single test show behavioral and functional deficits in the first two days after SAH in parallel to histological alterations indicating neuronal damage. In summary these tests can be used as functional outcome parameters in the anterior injection model of SAH.

Time course of cerebral blood flow velocity in central nervous system infections. A transcranial Doppler sonography study.

In a 3-year period, 110 patients with central nervous system infections of various causes were examined serially by means of transcranial Doppler sonography. In viral-induced infections, no changes of flow velocity in basal cerebral arteries were seen, whereas in bacterial meningitis, a significant increase of blood flow velocity in the middle cerebral artery was recorded. Its extent was mainly associated with the type of the infectious agent, most frequently observed in pneumococcal meningitis (77%). The increase was up to 100% of the baseline values and was reversible in all cases. All patients were offered full-scale neurointensive care, and all subjects with bacterial meningitis were fully heparinized.

Poliomyelitic-like illness in central European encephalitis.

Central European encephalitis (CEE) may be accompanied by myeloradiculitic symptoms in up to 5% of patients. The authors report six patients with a myelitic form of CEE mimicking acute poliomyelitis with bulbar and arm predominance and a poor prognosis. Three patients died. Of the survivors, only one can perform most activities of daily living, but still needs assisted ventilation at night. Autopsy in one patient showed severe cervicothoracic inflammation with changes almost exclusively in anterior horn cells and roots, as typically seen in poliomyelitis.

Affinity of anti-GM1 antibodies in Guillain-Barré syndrome patients.

In this study, we investigated the affinity of anti-GM1 IgG antibodies as well as their IgG subclass distribution in a series of 38 patients with Guillain-Barré syndrome. In 7 sera elevated titres of IgG anti-GM1 antibodies could be detected. With respect to affinity there were two distinct groups of anti-GM1 antibodies: one group was of high affinity and did not cross-react with other glycolipids; the other group was of low affinity and cross-reacted with asialo-GM1. IgG1 was the predominant and almost exclusive subclass of high affinity anti-GM1 antibodies. Axonal degeneration occurred significantly more frequently in patients with high affinity anti-GM1 antibodies than in patients without anti-GM1 antibodies or in patients with low affinity anti-GM1 antibodies. The presence of anti-Campylobacter jejuni antibodies was not associated with a specific electrophysiological pattern. The prognosis was not dependent on the detection of any of the antibodies, whereas axonal loss and ventilation were associated with a poor prognosis.

Craniectomy in severe, life-threatening encephalitis: a report on outcome and long-term prognosis of four cases.

OBJECTIVE: To report the feasibility of craniectomy with duraplasty in four patients with life-threatening encephalitis and, in particular, their long-term outcome. DESIGN: Report of four cases, analysis of the acute clinical course and neurological long-term sequelae. RESULTS: Generous craniectomy with duraplasty was performed in four patients with life-threatening encephalitis leading to decortication and decerebration. This treatment approach reduced intracranial pressure. The long-term sequelae (1.5-8 years after craniectomy) confirmed its appropriateness, having led to full neurological (cerebral) function, resocialization, and reintegration into their professional life in all four patients. CONCLUSION: Craniectomy with dural augmentation is a treatment approach in cases of severe space-occupying encephalitis, not only saving the patient's life but also leading to favorable long-term outcome.

Impaired microcirculation and tissue oxygenation in human cerebral malaria: a single photon emission computed tomography and near-infrared spectroscopy study.

Serial single photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were performed to investigate changes of cerebral perfusion and tissue oxygenation in a patient with complicated cerebral malaria that have been acquired in Nigeria. On admission to the Neurologic Intensive Care Unit in Innsbruck, Austria, SPECT and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen saturation, respectively, correlating exactly to the patient's right hemispheric localizing signs. In contrast, TCD examinations of the basal cerebral vessels revealed normal flow patterns. The patient showed an initial Plasmodium falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral mefloquine therapy. He was discharged without neurologic symptoms. Follow-up SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation patterns in both cortical hemispheres. In summary, the presented findings provide first evidence that noninvasive SPECT and NIRS may be important diagnostic tools in the evaluation of impaired cerebral microcirculation in patients with P. falciparum malaria.

Isolated pontine lesion in algid cerebral malaria: clinical features, management, and magnetic resonance imaging findings.

Malaria, the most important of all tropical diseases, causes approximately one million deaths per year. In Plasmodium falciparum malaria, the organs most affected are the brain, kidneys, lungs, and liver. Cerebral involvement is the most important lethal complication with a mortality rate of up to 50%. We report a patient with malignant, tertian falciparum malaria with an initial parasitemia rate of 60% and severe cerebral, hepatorenal, and pulmonary involvement. In addition to the severe diffuse encephalopathy, an initial neurologic examination showed signs of a pontine lesion that was confirmed by cerebral magnetic resonance imaging. We therefore conclude that cerebral malaria may be responsible for focal neurologic lesions that can be demonstrated by this procedure.

Cerebral blood flow velocity and perfusion in purulent meningitis: a comparative TCD and 99M-TC-HMPAO-SPECT study.

In 15 patients (median age 33 years; range 17-74 years) suffering from acute pneumococcal (10 cases) and meningococcal (five cases) meningitis, cerebral blood flow velocity (CBFV) was measured in the M1 - segment of the middle cerebral artery (MCA) by transcranial Doppler sonography, and cerebral perfusion changes were evaluated by 99m-Tc-hexamethylpropylene amine oxime single photon emission computed tomography (HMPAO SPECT). The objective of the study was to test whether increased CBFV during the acute phase of purulent meningitis reflects hyperemia, and to evaluate focal perfusion abnormalities and their correlation to CBFV changes. In eight patients with marked side-differences in CBFVs during the acute phase of the disease SPECT scans were normal in five. In three patients unilateral perfusion defects correlated with the side of higher CBFV. In seven patients presenting with symmetrically elevated CBFV, SPECT scans were normal in four and revealed focal abnormalities in the remaining three. Follow up SPECT scans were normal in 14/15 patients. The results of our study suggest that elevated CBFV in acute bacterial meningitis does not reflect cerebral hyperemia. Focal cerebral perfusion defects occur independently from functional alterations in the cerebral macrovasculature. A causative pathophysiologic relationship of high CBFV and focal perfusion defects cannot be drawn from these data.