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.

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.

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.

[Infections of the central nervous system in the immuno-compromised]. / Infektionen des ZNS beim immuninkompetenten Patienten.

Infections of the central nervous system (CNS) can be caused by a variety of pathogens, depending on whether the number and function of T-cells or monocytes are impaired (as in HIV patients) or whether the number and function of polymorphonuclear granulocytes are reduced or impaired, as typically seen in patients on immunosuppressive therapy, post transplantation, etc.. The first part of the chapter deals with CNS infections associated with reduced or abnormal T-cell (or monocytic) function and number, mainly seen in HIV patients, such as cerebral toxoplasmosis, CNS cryptococcosis, cytomegalovirus encephalitis, and progressive multifocal leukoencephalopathy. The clinical presentation, diagnostic procedures, as well as therapeutic and prophylactic management of these diseases are described in detail. The second part of the chapter deals with diseases usually seen in patients with impaired or reduced number and function of polymorphonuclear granulocytes. Such CNS infections are frequently caused by viral, bacterial, or fungal pathogens and are described in their clinical presentation, their diagnostic procedures and the best possible therapeutic and prophylactic management.

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.

Subcortical deficit pattern after brain abscess: a neuropsychological study.

The consequences of brain abscess (BA) on cognition and behaviour have never been examined in detail. The aim of this study was to determine the long-term cognitive deficits of patients who suffered a BA and to estimate its effect on the quality of life. Twenty patients were included in the study. Follow up with neuropsychological and behavioural tests was performed 6 months to 42 years after BA (mean 10.4 +/- 11.9). Cognitive deficits were defined as a test score of 2 or more standard deviations below controls' mean in those tasks which revealed a significant group deficit. Compared with healthy age, sex and education-matched controls, 13 of 20 patients (65%) exhibited neuropsychological deficits in some cognitive tasks. Ten of those patients (50%) were significantly impaired in < or =2 cognition domains, whilst the remaining three patients (15%) showed three to five impaired domains. No correlation was found between neuropsychological impairments and patients' age, sex, initial neurological symptoms, size and localization of BA, or secondary epileptic seizures. Reduction in quality of life was found in five patients (25%). BA may cause long lasting cognitive deficits. Despite the focal character of the lesion, long-term sequelae follow a more diffuse subcortical deficit pattern.

Refractory status epilepticus due to acute hepatic porphyria in a pregnant woman: induced abortion as the sole therapeutic option?

A 22-years old, 55 kg female patient in the twelfth week of pregnancy developed neuropsychiatric syndromes and in the following status epilepticus. Raised porphyrines and porphyrine precursors were found in the patient's urine. Despite intravenous glucose infusions and appropriate medication no reduction in seizure-frequency and neuropsychiatric syndromes was observed. An abortion was induced. After the interruption and starting of haem arginate therapy, seizure activity stopped and porphyrine precursors returned to normal levels, and after 6 weeks the patient was discharged in excellent clinical condition. This report describes a status epilepticus caused by acute hepatic porphyria, triggered by pregnancy, in a 22-years old woman. To our knowledge this is the first report of induced abortion as successful treatment in acute hepatic porphyria induced status epilepticus.

Cell index--a new parameter for the early diagnosis of ventriculostomy (external ventricular drainage)-related ventriculitis in patients with intraventricular hemorrhage?

UNLABELLED: Temporary intraventricular catheters for managing acute obstructive hydrocephalus caused by intraventricular haemorrhage carry a high risk of developing ventriculostomy-related ventriculitis (VRV). The aim of this prospective study was to validate a new parameter for the early detection of an intraventricular infection. METHODS: Patients with external ventricular drainage due to intraventricular haemorrhage were enrolled in this prospective study. Leucocytes and erythrocytes in cerebrospinal fluid (CSF) and peripheral blood as well as bacteriological and chemical analysis of both were examined daily. The ratio of leucocytes to erythrocytes in CSF and leucocytes to erythrocytes in peripheral blood was calculated (so called cell index (CI)) and these values were compared with the "conventionally diagnosed" drain-associated ventriculitis. Furthermore, the CI values of the non-ventriculitis and ventriculitis group were compared using the t-test with adjustment for unequal variances (Welch test). RESULTS: Thirteen patients with an external ventricular drainage (EVD) expected to be in place for more than seven days were enrolled. Seven patients developed a bacteriologically proven VRV (time 0) within 12 days (mean 8.57). Diagnosis of VRV by CI was possible up to 3 days (mean 2.28) prior to conventional diagnosis. P values (Welch test) showed a significant difference on days -3 (P = 0.03), -2 (P = 0.03) and -1 (P = 0.012) - i.e. 3, 2 or 1 day, respectively, prior to the time point when the CSF culture grew staphylococci -, when compared with the mean cell indices of the controls, and a highly significant difference on time 0 (P < 0.001). CONCLUSION: The calculated CI allows the diagnosis of nosocomial VRV in patients with intraventricular haemorrhage at a very early point of time.