[Management of oral anticoagulation related intracerebral hemorrhage]. / Management von intrazerebralen Blutungen unter oraler Antikoagulation.

The incidence of intracerebral hemorrhage (ICH) in patients using oral anticoagulation (OAC) will continue to increase with the demographic change of an aging population. As compared to primary spontaneous ICH, OAC-ICH is characterized by larger hematoma volumes, more frequent hematoma enlargement and intraventricular hemorrhage resulting in an even worse prognosis. Specific treatment should focus on immediate reversal of anticoagulation in addition to the basic acute management of ICH. In ICH patients using vitamin K antagonists (VKA), complete anticoagulant reversal with an international normalized ratio (INR) <1.3 should be achieved as quickly as possible using prothrombin complex concentrate (PCC) with additional substitution of vitamin K. Patients with ICH under dabigatran treatment should receive idarucizumab. In ICH patients using factor-Xa inhibitors, andexanet should be administered as soon as approved in Europe or within clinical studies and if unavailable alternatively high-dose PCC administration. Regarding OAC resumption, results from randomized trials are pending. In comprehensive observational studies and meta-analyses ICH patients resuming OAC showed a reduced incidence of thromboembolic events and mortality without significantly increased rates of hemorrhagic complications. Non-vitamin K dependent oral anticoagulants (NOAC) might further increase the safety of OAC resumption, which should be initiated after 4-8 weeks for patients with atrial fibrillation. In contrast, VKA resumption in patients with mechanical heart valves should not take place earlier than 1 week after ICH. Generally, safety of OAC resumption appears to be affected by ICH localization along with the presence of cerebral microbleeding, cortical superficial siderosis and cortical/convexity subarachnoid hemorrhage, making it crucial to weigh up the individual patient risk with respect to thromboembolic versus hemorrhagic events.

[Specialized neurological neurosurgical intensive care medicine]. / Spezialisierte neurologische neurochirurgische Intensivmedizin.

In Germany dedicated neurological-neurosurgical critical care (NCC) is the fastest growing specialty and one of the five big disciplines integrated within the German critical care society (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin; DIVI). High-quality investigations based on resilient evidence have underlined the need for technical advances, timely optimization of therapeutic procedures, and multidisciplinary team-work to treat those critically ill patients. This evolution has repeatedly raised questions, whether NCC-units should be run independently or better be incorporated within multidisciplinary critical care units, whether treatment variations exist that impact clinical outcome, and whether nowadays NCC-units can operate cost-efficiently? Stroke is the most frequent disease entity treated on NCC-units, one of the most common causes of death in Germany leading to a great socio-economic burden due to long-term disabled patients. The main aim of NCC employs surveillance of structural and functional integrity of the central nervous system as well as the avoidance of secondary brain damage. However, clinical evaluation of these severely injured commonly sedated and mechanically ventilated patients is challenging and highlights the importance of neuromonitoring to detect secondary damaging mechanisms. This multimodal strategy not only requires medical expertise but also enforces the need for specialized teams consisting of qualified nurses, technical assistants and medical therapists. The present article reviews most recent data and tries to answer the aforementioned questions.

[Intensive care therapy of space-occupying large hemispheric infarction. Summary of the NCS/DGNI guidelines]. / Intensivtherapie des raumfordernden ischämischen Hemisphäreninfarkts. Zusammenfassung der NCS/DGNI-Leitlinie.

Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference.

Advances in the management of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most detrimental sub-types of stroke and accounts for 10-15% of all strokes Qureshi et al. (Lancet 373(9675):1632-1644, 2009). ICH has an incidence of 10-30 cases per 100,000 people/year which is increasing and expected to double by the year 2050 Qureshi et al. (N Engl J Med 344 (19):1450-1460, 2001). Mortality rates still remain poor (30-50%) and functional dependency after ICH is high (~75%) van Asch et al. (Lancet Neurol 9 (2):167-176, 2010). Up to now, all randomized controlled trials investigating treatment approaches in ICH have failed to document improvements on clinical endpoints Mayer et al. (N Engl J Med 358 (20):2127-2137, 2008); Brouwers and Goldstein (Neurotherapeutics 9 (1):87-98, 2012). Only a specialized treatment of severely injured patients at dedicated neuro intensive care units [NICU] has been shown to be beneficial Qureshi et al. (Lancet 373(9675):1632-1644, 2009); Suarez et al. (Crit Care Med 32 (11):2311-2317, 2004). Currently, ongoing trials are investigating aggressive blood pressure lowering, hemostatic therapies, different operative strategies, intraventricular thrombolysis as well as neuroprotective approaches, and brain edema therapies. This review will summarize advanced treatment strategies and novel approaches which are currently under investigation.

Waiting for platelet counts causes unsubstantiated delay of thrombolysis therapy.

BACKGROUND: Platelet counts (PCs) <100,000/µl are considered as a contraindication for intravenous thrombolysis (IVT). While US guidelines recommend IVT initiation before the availability of clotting tests, the guidelines of the European Stroke Organization give no such practical advice. We aimed to assess the incidence of thrombocytopenia in IVT patients, outcome after thrombolysis in affected patients and the time gained by initiating treatment prior to availability of PC results. METHODS: All patients with thrombocytopenia were identified in our prospectively acquired thrombolysis database. Baseline demographic data, intracerebral hemorrhage rates as well as functional outcome were assessed. The median time between initiation of thrombolysis and availability of PCs was calculated. RESULTS: Of 625 IVT patients, 3 (0.5%) had thrombocytopenia at stroke onset. None of them developed intracerebral hemorrhage (ICH) or died during the follow-up. Waiting for PCs would have delayed treatment in 72.4% of the patients, with a median hypothetical delay of 22 min (interquartile range: 11-41 min). CONCLUSIONS: To date, there are no sufficient data to evaluate the ICH risk in thrombocytopenic patients. However, thrombocytopenia is rare in IVT patients. Thus, generally waiting for PC results prior to initiation of IVT is not warranted. Avoiding this significant delay yields shorter door-to-needle times and potentially more effective treatment.

Comparison of edoxaban and enoxaparin in a rat model of AlCl3-induced thrombosis of the superior sagittal sinus.

Cerebral sinus venous thrombosis (CSVT) is an uncommon disease that is usually treated with anticoagulation (heparin, low-molecular heparin, or vitamin K-antagonists). We compared treatment with edoxaban, an oral factor Xa-antagonist, that has not been approved in patients with CSVT, with enoxaparin, a well-established therapy, in a rat model of CSVT. Fifty male Wistar rats were randomized into 5 groups (10 animals each) and subjected to aluminum chloride (AlCl3)-induced thrombosis of the superior sagittal sinus (SSS) or sham procedure. Animals with thrombosis of the SSS were treated with edoxaban, enoxaparin, or placebo. Diagnostic workup included neurological examination, MRI imaging, MR-flow measurements of the SSS, and immunohistochemical staining. Neurological examination revealed no differences between treatment groups. Seven days after initial thrombosis, flow in the SSS was lower in the active treatment group as compared to sham-operated animals (p < 0.05). Flow in the SSS in the active treatment groups (edoxaban 1 h prior to thrombosis: 0.16 cm/s ± 0.06 cm/s; edoxaban 6 h after thrombosis: 0.13 cm/s ± 0.05 cm/s; enoxaparin: 0.13 cm/s ± 0.04 cm/s; placebo: 0.07 cm/s ± 0.02 cm/s) was higher as compared to placebo (p < 0.05), but there were no differences between the active treatment groups (p > 0.05). Immunohistochemical staining showed no differences in the actively treated animals. Edoxaban proved to be similar to enoxaparin in a model of experimental AlCl3-induced CSVT.

Characteristics and outcome of patients with early complete neurological recovery after thrombolysis for acute ischemic stroke.

BACKGROUND: Recombinant tissue plasminogen activator (rt-PA) is the only approved specific therapy for acute ischemic stroke. This study analyzes demographic and clinical characteristics of patients with early complete neurological recovery after thrombolysis. METHODS: Data of 320 consecutive patients treated with rt-PA within 3 h of stroke onset at our facility between April 2006 and March 2009 were extracted from our prospective institutional stroke and thrombolysis database. Baseline demographic parameters, risk factors, clinical characteristics as well as neuroradiologic findings of patients with complete recovery 24 h after treatment and at hospital discharge were analyzed. Outcome was evaluated using the modified Rankin Scale at 90 days. RESULTS: Thirty patients (9.4%) were asymptomatic 24 h after thrombolysis and 70 (22%) at hospital discharge. Patients with complete recovery were younger, more often male, had milder stroke symptoms, less often cardioembolic strokes, fewer bleeding complications and more often normal follow-up imaging. In addition, in-hospital time was shorter and these patients retained a better functional outcome at 90 days. Only 1 patient who had completely recovered at hospital discharge died during the follow-up time. In multivariate regression analysis, only the National Institute of Health Stroke Score (NIHSS) on admission was predictive for complete recovery at both examined time points. CONCLUSION: Rapid complete recovery can be achieved in up to a fifth of acute stroke patients treated with thrombolysis. These patients are younger and have milder strokes, less often with cardioembolic origin. Better outcome and lower mortality are sustained at 3 months.

Intravenous thrombolysis in posterior cerebral artery infarctions.

BACKGROUND: Approximately 5-10% of all acute ischemic strokes (AIS) occur in the territory of the posterior cerebral artery (PCA). Little is known about intravenous thrombolysis (IVT) in this infarct subgroup in terms of outcome and intracerebral hemorrhage rates. The aim of our study was to evaluate differences between supratentorial PCA infarcts and anterior circulation infarcts regarding baseline characteristics, stroke severity, outcome, safety and clinical findings, which would implicate a change in the existing thrombolysis practice in patients with PCA stroke. METHODS: All patients with AIS in the supratentorial PCA territory receiving IVT between 01/2006 and 01/2010 were selected from the Erlangen Thrombolysis Database (group 1, n = 21). They were compared to all IVT patients with strokes in other supratentorial vascular territories over the same period of time (group 2, n = 398). Baseline demographic data, as well as clinical and laboratory findings were analyzed. The outcome was assessed using the modified Rankin Scale at 3 months. RESULTS: Only serum glucose levels at baseline (110.5 ± 36.1 vs. 127.2 ± 48.2 mg/dl; p = 0.036) and the baseline National Institutes of Health Stroke Scale score (median 6.5 vs. 9; p = 0.016) were significantly lower in group 1 compared to group 2. Favorable clinical outcome (57.1 vs. 48.6%; p = 0.445) and intracerebral hemorrhage rates (4.8 vs. 4%; p = 1.000) were comparable in both groups. CONCLUSIONS: No substantial differences were found between supratentorial PCA and anterior circulation infarcts. Our data on safety and efficacy support the present common thrombolysis practice in supratentorial PCA infarct patients, though an indication for IVT should rather be based on the existence of functionally disabling deficit than merely on the National Institutes of Health Stroke Scale.

Off-label thrombolysis for acute ischemic stroke: rate, clinical outcome and safety are influenced by the definition of 'minor stroke'.

BACKGROUND: Several contraindications for intravenous thrombolysis are not based on controlled trials. Specialized stroke centers often apply less restrictive criteria. The aim of our study was to analyze how many patients at our institution receive off-label thrombolysis. In addition, clinical outcome and safety data were compared to those from patients treated on-label, and the influence of different definitions of 'minor stroke' were examined. METHODS: Consecutive thrombolysis patients treated between January 2006 and January 2010 were included. Patients treated off-label were compared to patients given on-label therapy according to the European license. Since no specified definition for 'minor neurological deficit' exists in the license, two distinct definitions were considered off-label, i.e. National Institutes of Health Stroke Scale score (NIHSSS) <1 (definition 1) and NIHSSS ≤4 (definition 2). RESULTS: Of a total of 422 patients, 232 (55%) were treated off-label. The most prevalent off-label criteria (OLCs) were the following: age >80 years (n = 113), minor stroke (definition 1, n = 3; definition 2, n = 84), elevated blood pressure necessitating aggressive treatment (n = 75), time window >3 h (n = 71) and major surgery or trauma within the preceding 3 months (n = 20). In group comparisons, off-label patients had an overall worse outcome using definition 1 for minor stroke, while there was no difference when definition 2 was applied. In multivariate analysis, off-label therapy (definition 1) in general and age >80 years were independent predictors of poor outcome. None of the contraindications were associated with an increased bleeding risk. CONCLUSIONS: Off-label therapy is frequently applied at our center and is not associated with higher complication rates. Overall outcome of off-label treatment largely depends on the definition used for minor stroke. Besides age >80 years, a known poor prognostic factor, no other specific OLC was associated with poor outcome. Our data suggest that the criteria in the European license may be too restrictive.

Single versus bilateral external ventricular drainage for intraventricular fibrinolysis in severe ventricular haemorrhage.

BACKGROUND: Intraventricular fibrinolysis (IVF) through bilateral external ventricular drains (EVD) may provide better access of the thrombolytic agent to the intraventricular clot, potentially influencing clot clearance and outcome. METHODS: Patients with spontaneous ganglionic intracerebral haemorrhage (ICH)<40 cm(3) and intraventricular haemorrhage (IVH) with acute hydrocephalus have been treated with IVF. The decision for placement of one or two EVDs has been left to the discretion of the treating physician. CT volumetry, the effects on cerebrospinal fluid (CSF) circulation and outcome at 3 months have been analysed for patients with one (group I, n = 13) or two EVDs (group II, n = 14). RESULTS: No difference was found in clot resolution between the two groups (clot half life 2.1 (SD 1.2) vs 2.4 (1.3) days). A separate analysis of the third and fourth ventricle clearance was similar (1.6 (0.6) versus 1.8 (0.8) days), indicating no difference in reconstitution of CSF circulation. A trend towards a longer EVD duration and higher infection rate was found in the bilateral EVD group. No difference was found in outcome at 3 months. CONCLUSIONS: Our results do not support the use of bilateral EVDs for IVF in patients with severe IVH.

[Wake up stroke: Overview on diagnostic and therapeutic options for ischemic stroke on awakening]. / "Wake-up Stroke": Ubersicht zu diagnostischen und therapeutischen Optionen des aus dem Schlaf heraus aufgetretenen ischämischen Schlaganfalls.

Up to 25 % of all acute ischemic strokes (AIS) occur during sleep with the patients or relatives becoming aware of their neurological deficits as they wake up. Because of the unclear time of stroke onset patients with stroke on awakening are usually not considered for acute therapies and excluded from most treatment trials. We give an overview of the published data regarding ischemic wake up strokes (WUS). In particular we focused on baseline characteristics, imaging methods and therapy strategies. Comparing WUS patients and patients with known stroke onset there were no major differences found regarding patient characteristics, etiology, clinical and radiological characteristics. Even though there is no existing gold standard multiparametric neuroimaging (CT; MRI) appears to be helpful for decision making whether to treat a WUS patient with thrombolysis or not. Especially multiparametric MRI which proved to be safe in patients within an extended time window might serve as an adequate diagnostic tool. The results of first pilot studies analyzing treatment of WUS demonstrate that a substantial number of these patients can be treated with IV thrombolysis (IVT) successfully. Large randomized, controlled, prospective clinical trials for patients with WUS are needed to test safety and efficacy of IVT and to evaluate the assumed benefit of multiparametric neuroimaging techniques in this patient group. The results of first pilot studies may be instrumental to help plan and design such trials.

A Sphingosine-1-Phosphate Receptor Modulator Attenuated Secondary Brain Injury and Improved Neurological Functions of Mice after ICH.

BACKGROUND: Stroke activates the immune system and induces brain infiltration by immune cells, aggravating brain injury. Poststroke immunomodulation via (S1P-)receptor modulation is beneficial; however, the S1P-modulator in clinical use (FTY-720) is unspecific, and undesirable side effects have been reported. Previously, we tested effects of a novel selective S1P-receptor modulator, Siponimod, on ICH-induced brain injury in acute stage of the disease. In the current study, we investigated whether protective effects of Siponimod, evaluated in a short-term study, will protect the brain of ICH animals at long term as well. METHODS: 134 C57BL/6N mice were divided into sham and ICH-operated groups. Collagenase model of ICH was employed. ICH animals were divided into Siponimod treated and nontreated. Dose- and time-dependent effects of Siponimod were investigated. Contraplay between development of brain injury and the number of lymphocytes infiltrating the brain was investigated by forelimb placing, T-Maze test, brain water content calculation, MRI scanning, and immunostaining. RESULTS: Depending on the therapeutic strategy, Siponimod attenuated the development of brain edema, decreased ICH-induced ventriculomegaly and improved neurological functions of animals after ICH. It was associated with less lymphocytes in the brain of ICH animals. CONCLUSION: Siponimod is able to decrease the brain injury and improves neurological functions of animals after ICH.

Serelaxin activates eNOS, suppresses inflammation, attenuates developmental delay and improves cognitive functions of neonatal rats after germinal matrix hemorrhage.

Germinal matrix hemorrhage (GMH) is a detrimental form of neonatal CNS injury. Following GMH-mediated eNOS inhibition, inflammation arises, contributing to GMH-induced brain injury. We investigated the beneficial effects of Serelaxin, a clinical tested recombinant Relaxin-2 protein, on brain injury after GMH in rats. We investigated whether effects of Serelaxin are mediated by its ability to activate the GMH-suppressed eNOS pathway resulting in attenuation of inflammatory marker overproduction. GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U). Seven day old Sprague-Dawley rat pups (P7) were used (n = 63). GMH animals were divided in vehicle or serelaxin treated (3 µg once, 30 µg once, 30 µg multiple, i.p., starting 30 after GMH and then daily). Sham operated animals were used. We monitored the developmental profile working memory and spatial function (T-maze and open field test respectively). At day 28, all rats underwent MRI-scans for assessment of changes in cortical thickness and white matter loss. Effects of Serelaxin on eNOS pathway activation and post-GMH inflammation were evaluated. We demonstrated that Serelaxin dose-dependently attenuated GMH-induced developmental delay, protected brain and improved cognitive functions of rats after GMH. That was associated with the decreased post-GMH inflammation, mediated at least partly by amelioration of GMH-induced eNOS inhibition.

Evolution of stroke diagnosis in the emergency room--a prospective observational study.

BACKGROUND: Access to acute neurological care is limited. Especially in nonurban areas, and owing to uncertainties in diagnosing stroke, non-neurologists often misinterpret stroke symptoms. We evaluated the profile of patients with suspected stroke and the accuracy of the admission diagnosis 'stroke' in the setting of a specialized neurological emergency department in a nonurban region. METHODS: In this prospective observational study, (1) data from all 4,174 patients with the discharge diagnosis 'stroke' and (2) data from 1,800 consecutive patients (3 cohorts per year over 3 years) with the admission diagnosis 'stroke' were included over a 3-year period. RESULTS: The positive predictive value of the admission diagnosis 'stroke' was 0.34; the negative predictive value was 0.97. The rate of misdiagnosis significantly correlated with age and time from symptom onset to presentation. During the study period, the proportion of patients with the admission diagnosis 'stroke' admitted early after symptom onset increased from 19.9 to 27.8% within 3 h and from 26.4 to 32.7% within 4.5 h, respectively. Thrombolysis rates increased (from 9.4 to 15.4%). CONCLUSION: The uncertainties in interpreting stroke symptoms and the lack of facilities for treating emergency stroke in nonurban areas may be outweighed by offering access to a specialized neurological emergency room, thus rectifying any misinterpretation of stroke symptoms and shortening in-hospital time windows for treatment. Still, the rate of misdiagnosis is high, requiring expensive resources, despite the constant flow of information to the public. Therefore, more prospective data comparing different emergency room settings are needed which focus in particular on patients with the admission diagnosis 'stroke'.

Safety and outcome after thrombolysis in stroke patients with mild symptoms.

BACKGROUND: Thrombolytic therapy is frequently withheld in patients with minor stroke symptoms. However, recent studies demonstrate that a substantial proportion of these patients dies or remains permanently disabled because of underestimation of symptom severity at baseline or secondary deterioration. We aimed to assess the safety and outcome of thrombolysis therapy in patients with minor but disabling stroke symptoms. METHODS: 32 patients presenting with mild symptoms were treated with intravenous recombinant tissue-type plasminogen activator between April 2006 and April 2008. Data were extracted from a prospectively collected database. Baseline demographic data, and clinical, laboratory and imaging findings were analyzed. Outcome was assessed using the modified Rankin Scale (mRS) score at 3 months and was dichotomized into favorable (mRS 0-1) versus unfavorable (mRS 2-6). RESULTS: In the majority of patients, the left hemisphere was affected, with aphasia representing the most common symptom leading to treatment decision. The frequency of perfusion lesion (46%) and vessel occlusion (35%) at baseline was high but had no effect on the outcome at 3 months in our series of treated patients. Outcome was favorable in 94% of patients, and 47% recovered without any persisting symptom. Only one asymptomatic and no symptomatic hemorrhage was observed. CONCLUSION: Our data support current guidelines and international licenses which give no lower National Institutes of Health Stroke Scale (NIHSS) limit for intravenous thrombolysis (IVT). Considering the accumulating evidence that the natural course in patients with mild symptoms is not as favorable as often assumed and taking the low risk of bleeding in those patients into account, patients with mild but disabling symptoms should be treated with IVT regardless of their baseline NIHSS score.

Influence of intraventricular fibrinolytic therapy with rt-PA on the long-term outcome of treated patients with spontaneous basal ganglia hemorrhage: a case-control study.

Over the recent years, fibrinolytic agents have been tested for intraventricular clot fibrinolysis (IVF). Compared with patients who did not receive IVF, administration of rt-PA induces rapid resorption of intraventricular blood and normalization of cerebrospinal fluid (CSF) circulation resulting in a reduced 30-day mortality and beneficial short-term outcome after 3 months. Our objective was to analyze possible influences of IVF on the long-term outcome after 12 months. Based on a prospective data base, patients with ganglionic supratentorial hematoma with additional intraventricular hemorrhage and occlusive hydrocephalus (n = 135) were isolated. Twenty-seven patients received IVF. To design a case-control study, we carefully matched 22 controls without IVF with regard to hematoma volume, Graeb score, Glasgow Coma Scale on admission and age (five patients remained unmatchable). We determined clinical and imaging parameters by reviewing the medical records and CT scans of all included patients. Outcome after 12 months was evaluated using the modified Rankin scale (mRS). One multivariate regression analysis was performed to determine predisposing factors for outcome. IVF significantly reduced Graeb score during treatment (eight on admission, three after IVF, one prior to discharge in the treated group versus 8/6/2 in patients without IVF). In patients with IVF requirement, a second external ventricular drainage (EVD) and a ventriculoperitoneal (VP) shunt were reduced (P = 0.08) and the incidence of a lumbar drainage was significantly higher (P < 0.01), whilst the overall time of extra-corporal CSF drainage was comparable. EVD associated complications were equal in both groups. Overall long-term outcome was poor but no significant differences were found between patients with and without IVF (mRS 4-6: 12/22 (54%) in patients with and 13/22 (59%) in patients without IVF; P = 0.81). The five excluded patients with IVF were similar to the 22 included ones with respect to imaging findings and outcome. The multivariate analysis revealed age and baseline hematoma volume, but not IVF to significantly impact the outcome. In accordance with previous studies, IVF hastened clot lysis and reduced the need for repeated EVD exchanges and permanent shunting. However, despite these advantages, IVF did not influence long-term outcome after 12 months. The results of the prospective randomized trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) need to be awaited.

In vivo detection of hepatitis C virus (HCV) RNA in the brain in a case of encephalitis: evidence for HCV neuroinvasion.

We report here a 27-year-old woman who presented with encephalitis of unknown origin. Magnetic resonance imaging (MRI) of the brain revealed leukoencephalopathy, cerebrospinal fluid showed signs of inflammation. Serum and brain biopsy tissue was tested positive for hepatitis C virus (HCV). Neuropathological investigation supported the hypothesis of viral encephalitis. C3, C4 and cryoglobulins as well as cerebral MR-angiography were normal. Neurological complications of HCV infection other than hepatic encephalopathy are generally attributed to parainfectious phenomena. This is the first case of HCV-RNA detection in vivo in human brain in literature and it raises the possibility that HCV is able to induce encephalitis caused by neurotrophism. This is supported by the fact that there is a growing body of literature on HCV-induced cerebral dysfunction and laboratory findings indicating HCV neuroinvasion.