Recurrent stroke after lobar and deep intracerebral hemorrhage: a hospital-based cohort study.

BACKGROUND: Recurrent stroke rates after intracerebral hemorrhage (ICH) vary widely between observational studies due to differences in ICH etiology and risk for thromboembolic events. We therefore aimed to assess the patient characteristics and prognosis after deep and lobar ICH in a well-characterized, multicenter, hospital-based cohort. METHODS: Patients were prospectively documented in 13 German neurological stroke centers. Of 744 patients with spontaneous ICH discharged alive, 516 (69.4%) gave informed consent and 496 (66.7%) could be followed up by central telephone interview over a mean duration of 2 years. RESULTS: In patients with deep ICH, the Kaplan-Meier estimate for stroke during the first year was 5.8% (95% CI 2.9-8.7) and the overall annual rate (calculated over a 3-year period) was 2.9% (95% CI 1.6-4.1). In patients with lobar ICH, the Kaplan-Meier estimate for stroke during the first year was 7.8% (95% CI 3.1-12.5) and the overall annual rate was 7.2% (95% CI 3.8-10.6). At the last follow-up before recurrent stroke or end of study, 141 patients (28.4%) overall received antiplatelet agents, and 12 (2.4%) received oral anticoagulation. No difference could be found for recurrent ICH under antiplatelet agents versus no antithrombotic medication. CONCLUSION: The risk of recurrent stroke after lobar ICH remains high beyond the first year, whereas it decreases after 1 year in patients with deep ICH. Antiplatelets are prescribed in a considerable number of patients even though the risk-benefit ratio after ICH remains unknown.

[Aggressive immunotherapy in Susac's syndrome]. / Aggressive Immuntherapie beim Susac-Syndrom.

Susac's syndrome is a rare but important differential diagnosis of aseptic encephalitis of young women with focal neurological deficits and white matter lesions on cerebral MRI. We report on a previously healthy 36-year-old woman who presented with encephalopathy, central weakness of her right leg and multiple white matter lesions on MRI. Shortly thereafter, inner ear deafness developed and funduscopy revealed occlusions of branch retinal arteries. A diagnosis of retino-cochlear-cerebral vasculopathy or Susac's syndrome was established and steroid-based immunotherapy with high-dose corticosteroids was initiated. Steroid reduction led to repeated clinical worsening, so that immunotherapy was sequentially escalated. Finally, high-dose cyclophosphamide every 4 weeks led to sufficient control of disease activity. Recent publications have argued for an early and aggressive immunosuppression in Susac's syndrome based on clinical and histological similarities with juvenile dermatomyositis, where such a regimen has already been established. We report on these treatment guidelines with respect to the current literature and the case presented.

Effects of physiological aging and cerebrovascular risk factors on the hemodynamic response to brain activation: a functional transcranial Doppler study.

The influence of the vascular system on the coupling of cerebral blood flow (CBF) to focal brain activation during aging is incompletely understood. Using functional transcranial Doppler sonography and a hypercapnic challenge as a marker of intact cerebral vasoreactivity, we determined CBF velocity (CBFV) changes in response to a language and arithmetic task in a group of 43 healthy young subjects (mean age 32 +/- 8.6 years), 18 healthy old subjects (mean age 64 +/- 9.8 years) and 29 old subjects with risk factors for an atherosclerosis (mean age 69 +/- 8.4 years). Despite a similar performance during the cognitive tasks the CBFV changes were significantly lower in the group of old subjects with vascular risk factors compared with the healthy young and old subjects. Similarly, the CBFV changes during hypercapnia were significantly lower in the group of old subjects with vascular risk factors compared with the healthy young and old subjects. In contrast, both cognitive tasks and hypercapnia produced comparable CBFV changes in the group of healthy young and old subjects. These results suggest that the hemodynamic response to neuronal activation is unaffected by aging alone, whereas the presence of cardiovascular risk factors significantly diminishes the capability of cerebral vessels to react to vasodilating stimuli.

Cerebral haemodynamics during hypo- and hypercapnia: determination with simultaneous 15O-butanol-PET and transcranial Doppler sonography.

AIM: Transcranial Doppler sonography (TCD) is increasingly used in cerebrovascular disease for monitoring brain perfusion. It allows estimation of cerebral blood flow (CBF) by the measurement of cerebral blood flow velocity (CBFV). The CBFV as well as CBF are intimately associated with the intravascular CO2-concentration. Thus, hyper- or hypocapnia can be used to induce a defined range of blood flows. The aim of our study was the comparison of vasomotor reactivity assessed with simultaneous TCD and quantitative regional CBF-measurements (rCBF) by PET (serving as the reference method for in-vivo quantification of rCBF). PATIENTS, METHODS: Six healthy young volunteers participated in this study. CBF was measured using 15O-butanol PET. A flow and dispersion-model was fitted to the measured time activity curves using arterial input curves. Each subject underwent five scans at five different end-tidal CO2 levels (EtCO2): 25, 32, 40, 48, and 55 mmHg. CBFV was assessed by continuous bilateral TCD of the middle cerebral artery (MCA). Volumes of interest for rCBF determination were placed in grey matter of the prefrontal cortex (PFC) as determined from individual MRIs. Comparisons between the rCBF, EtCO2 and CBFV were carried out with regression and correlation analysis and paired t-tests. RESULTS: Strong positive linear correlations of rCBF and CBFV with the CO2-concentration and linear relationships between rCBF and CBFV were found in each individual. Normalised CO2-reactivities measured by TCD and PET were closely correlated. CONCLUSIONS: TCD-measurements of vascular reactivity in healthy volunteers show a high correlation to those acquired with PET that serves as the reference method of quantitative rCBF-measurement. The results of the MCA insonation are a close approximation of the rCBF changes induced by variations of EtCO2.

Multiple reversible MR signal changes caused by Epstein-Barr virus encephalitis.

This report presents the imaging findings of an unusual case of Epstein-Barr virus (EBV) encephalitis. A young man presented with a short-lasting history of febrile infection, neuropsychologic deficits, ataxia, and seizures. MR imaging revealed fully reversible signal intensities (T2, diffusion-weighted imaging with a decreased apparent diffusion coefficient) in the splenium of the corpus callosum and both posterior hemispheres. EBV infection must be added to the list of differential diagnoses of (reversible) splenial lesions.

Mechanical Recanalization following i.v. Thrombolysis: A Retrospective Analysis regarding Secondary Hemorrhagic Infarctions and Parenchymal Hematomas.

Introduction. In acute stroke by occlusion of the proximal medial cerebral artery (MCA) or the distal internal carotid artery, intravenous thrombolysis is an established treatment. Another option is mechanical recanalization. It remains unclear if the combination of both methods poses an additional bleeding risk. The aim of this retrospective analysis is to determine the proportion of hemorrhagic infarctions and parenchymal hematomas. Methods. Inclusion criteria were an occlusion of the carotid T or proximal MCA treated with full dose thrombolysis and mechanical recanalization. 31 patients were selected. Devices used were Trevo, Penumbra Aspiration system, Penumbra 3D Retriever, and Revive. The initial control by computed tomography was carried out with a mean delay to intervention of 10.9 hours (SD: 8.5 hours). Results. A slight hemorrhagic infarction (HI1) was observed in 2/31 patients, and a more severe HI2 occurred in two cases. A smaller parenchymal hematoma (PH1) was not seen and a space-occupying PH2 was seen in 2/31 cases. There was no significant difference in the probability of intracranial bleeding after successful (thrombolysis in cerebral infarctions 2b and 3) or unsuccessful recanalization. Conclusion. The proportion of intracranial bleeding using mechanical recanalization following intravenous thrombolysis appears comparable with reports using thrombolysis alone.

Dysfunction of vasomotor reactivity in severe sepsis and septic shock.

OBJECTIVE: Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock, leading to organ dysfunction. We investigated whether carbon dioxide (CO2)-induced vasomotor reactivity (VMR) is impaired in septic patients, compared with values obtained outside sepsis. DESIGN: Prospective, clinical study. SETTING: Six-bed neurologic critical care unit of a university hospital. PATIENTS AND PARTICIPANTS: Eight consecutive patients with severe sepsis and septic shock. MEASUREMENTS AND RESULTS: CO2-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy (NIRS). VMR was calculated as the percentage change of cerebral blood flow velocity (normalized CO2-reactivity, NCR) and absolute changes in concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin (HbO2, Hb, HbT) and Hbdiff (difference between HbO2 and Hb) in micromol/l per 1% increase in end-tidal CO2 (CR-HbO2, CR-Hb, CR-HbT, CR-Hbdiff). NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis (mean, SD, Wilcoxon): NCR 11.0 (7.1) versus 30.7 (13.0), p < 0.02; CR-HbO2 0.70 (0.61) versus 2.33 (1.11), p < 0.02; CR-Hb -0.17 (0.74) versus -1.42 (1.28), p < 0.04; CR-HbT 0.53 (0.48) versus 1.05 (0.40), p < 0.03; CR-Hbdiff 0.91 (1.33) versus 3.75 (2.33), p < 0.02. This indicates a severely disturbed VMR. CONCLUSIONS: In the advent of a disturbed cerebral autoregulation, critical drops in blood pressure during sepsis are transferred directly into the vascular bed, leading to cerebral hypoperfusion. This mechanism might contribute to the pathogenesis of septic encephalopathy.

Inhibition of ipsilateral motor cortex during phasic generation of low force.

OBJECTIVE: To study the effect of different types of unilateral pinch grips on excitability of the ipsilateral motor cortex. METHODS: In 9 healthy volunteers, transcranial magnetic stimuli (TMS) were applied over one motor cortex while the subjects performed either phasic or tonic ipsilateral pinch grips with different force levels (range 1-40% maximum voluntary contraction, MVC). Motor evoked potentials (MEP) were recorded from the relaxed contralateral first dorsal interosseous muscle (FDI) and were compared to MEPs obtained during muscle relaxation of both hands. In additional experiments, transcranial electrical stimuli (TES) were administered and F waves were recorded after electrical stimulation of the ulnar nerve. RESULTS: Phasic pinch grips with low force (1 and 2% MVC) induced a significant decrease of TMS-induced MEP amplitudes. The effect lasted for about 100 ms after reaching the force level and was similar for both right and left-handed pinch grips. TES-induced MEPs and F waves remained unchanged. In contrast, tonic contractions (20 and 40% MVC) enhanced MEPs in the homologous FDI. CONCLUSIONS: Phasic pinch grips with low force inhibit the motor cortex responsible for the contralateral homologous hand muscle. This effect, which is probably mediated transcallosally, might act at the level of the motor cortex.

[Septic encephalopathy]. / Septische Enzephalopathie.

Septic encephalopathy describes a diffuse cerebral dysfunction in association with sepsis. It is the most common cause of altered brain function in the intensive care unit setting but other causes have to be excluded. Alterations in the level of consciousness occur early and are common. Epileptic seizures may occur but asymmetric neurological findings are not typical. The pathophysiology of septic encephalopathy is diverse and not fully elucidated; however, perfusion abnormalities play an important role. Neuropathological findings are diffuse, widespread and often show features of ischemia and non-bacterial inflammation. Diagnostic procedures should exclude frequent differential diagnoses, such as stroke, meningitis or encephalitis. Cerebral computed tomography (CT) is usually unremarkable but magnetic resonance imaging (MRI) may reveal vasogenic edema in terms of a posterior reversible encephalopathy syndrome. Septic encephalopathy requires an adequate therapy of the sepsis syndrome but a specific therapy is not yet available.

IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment.

OBJECTIVE: To report that antibodies to synaptic proteins may occur in association with slow, progressive cognitive decline. METHODS: A total of 24 patients with progressive cognitive dysfunction of unclear etiology were examined for onconeuronal and synaptic receptor antibodies. The effect of serum was examined in cultures of dissociated mouse hippocampal neurons. RESULTS: Seven patients had immunoglobulin A (IgA), but no immunoglobulin G (IgG), antibodies against NMDA receptor (NMDAR). Anti-NMDAR IgA positive patients' serum, but not serum from control individuals, caused dramatic decrease of the levels of NMDAR and other synaptic proteins in neurons, along with prominent changes in NMDAR-mediated currents. These effects correlated with the titer of IgA NMDAR antibodies and were reversed after removing patients' serum from the culture media. When available, comprehensive clinical assessment and brain metabolic imaging showed neurologic improvement after immunotherapy. CONCLUSIONS: A subset of patients with slowly progressive cognitive impairment has an underlying synaptic autoimmunity that decreases the density of NMDAR and other synaptic proteins, and alters synaptic currents. This autoimmunity can be demonstrated examining patients' serum and CSF for NMDAR IgA antibodies, identifying possible candidates for immunotherapy.

Pharmacokinetics of 5-fluorouracil in patients heterozygous for the IVS14+1G > A mutation in the dihydropyrimidine dehydrogenase gene.

5-Fluorouracil (5FU) and capecitabine are two of the most frequently prescribed chemotherapeutic drugs for the treatment of patients with cancer. Administration of test doses of 5FU to eight patients heterozygous for the IVS14+1G > A mutation and five control patients showed that the AUC and clearance were weak parameters with respect to the identification of patients with a DPD deficiency. However, highly significant differences were observed for the terminal half life of 5FU between DPD patients and controls. Thus, a DPD deficiency could be predicted from 5FU blood concentrations measured after the administration of a test dose of 5FU.

The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features.

BACKGROUND: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities. METHODS: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both. RESULTS: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. CONCLUSIONS: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.

Aneurysm of the extracranial carotid artery with spontaneous echo contrast revealed by duplex sonography.

A 56-year old male patient without cerebrovascular disease or risk factors presented with a painless, pulsatile right-sided cervical swelling. Ultrasonography showed a large aneurysm of the right common and internal carotid artery with homogeneous thickening of the vessel wall as well as a parietal thrombus and a dilation of the left common and internal carotid artery with markedly reduced blood flow velocities. In the enlarged lumen of the right internal carotid artery spontaneous echo contrast was apparent with slow, ineffective but orthograde blood flow motions. Ensuing diagnostic procedures revealed multiple aneurysms involving the aorta and its branches. Despite surgical removal of the aneurysm and glucocorticoid therapy, the patient died from a ruptured aneurysm of a coronary artery a few weeks later. Post-mortem examination showed panarteritis consistent with Takayasu's disease. Spontaneous echo contrast is a frequent echocardiographic finding in patients with atrial fibrillation and mitral stenosis, indicating decreased blood flow. This is associated with an increased risk of embolism. In our patient, spontaneous echo contrast indicated severely disturbed haemodynamics due to a large aneurysm of the carotid artery. In the rare case of multiple aneurysms, differential diagnosis should include dissections, infections, and connective tissue diseases. Takayasu's arteritis, however, should also be considered, which usually presents with stenoses, but may be associated with multiple aneurysms of the aorta or its branches. If the diagnostic criteria are present, immunosuppressive treatment should be initiated.

[Selective immunoadsorption in neurologic complications of systemic lupus erythematosus]. / Selektive Immunadsorption bei neurologischen Komplikationen eines systemischen Lupus erythematodes.

Vasculitis of the nervous system is a rare cause of multifocal neurologic symptoms and may involve both the central and peripheral nervous systems. Typical symptoms include headache, encephalopathy with cognitive impairment and psychotic symptoms, epileptic seizures, and peripheral neuropathies. Here we report the case of a 71-year-old female presenting with Raynaud's syndrome and paresthesia of the feet. Several weeks later she was admitted to our hospital with a status epilepticus and complex partial seizures. On admission she had mild aphasia, distal paresis of the arms without sensory deficits, and disorientation with hallucinations. Cerebral MRI revealed small, multifocal infarctions in several arterial territories. Multiple cerebral artery stenoses were detected by ultrasound. Examination of the CSF was unremarkable. Serologic tests for autoimmune disorders detected Ro antibodies compatible with systemic lupus erythematosus or Sjögren's syndrome. A sural nerve biopsy revealed ischemic axonal neuropathy. During administration of i.v. methylprednisolone, the symptom progression stopped but dosages could not be tapered due to severe CNS symptoms (mental decline, disorientation, aphasia, hallucinations). Slow but sustained clinical improvement was achieved by immunoadsorption over 3 weeks followed by a combined high-dose immunosuppressive treatment with cyclophosphamide and prednisolone that paralleled a reduction in anti-Ro titers and normalization of cerebral blood flow velocities as detected by repeated transcranial Doppler sonography. Systemic vasculitis may present with multiple neurologic and psychiatric symptoms due to involvement of the central and peripheral nervous systems. After excluding systemic infection, immunosuppressive therapy should be started early. In our case a combination of high-dose methylprednisolone, immunoadsorption with elimination of Ro antibodies, and cyclophosphamide led to the patient's recovery.

[Bilateral hypoglossal nerve palsy following intubation]. / Bilaterale Hypoglossusparese nach Intubationsnarkose.

Hypoglossal nerve palsy following intubation is a rare complication that can be reversible depending on the extent of nerve damage. A 63-year-old male with a sigma carcinoma was repeatedly intubated orotracheally due to postoperative complications. After the fourth intubation, bilateral, complete hypoglossal nerve palsy with severe dysarthria and swallowing disability was observed. A percutaneous endoscopic gastrostomy tube was inserted for nutrition and to prevent aspiration. Cerebral MRI showed no pathological findings, particularly in the brainstem. Electromyographic studies revealed pathological spontaneous activity of both glossal muscles without any motor unit potential consistent with an axonal lesion of both hypoglossal nerves. Nevertheless, complete clinical and electromyographical recovery occurred within 7 months. The bilateral hypoglossal nerve palsy in our patient was probably due to mechanical alteration during intubation, leading to axonotmesis. Hypoglossal nerve palsy following intubation might have a favourable prognosis as long as continuity of the nerve sheath is maintained.

Outcome after decompressive craniectomy in patients with severe ischemic stroke.

Decompressive craniectomy after space occupying infarction of the middle cerebral artery (MCA) tends to decrease mortality and increase functional outcome. The aim of this retrospective study was to evaluate mortality rates and functional outcome in our centre and to identify predictors of prognosis. The charts of 30 consecutive patients (6 women, 24 men, mean age 59.3 +/- 11.0 years) who underwent craniectomy after space occupying MCA-infarction from 1996 to 2002 were analyzed. Functional outcome was assessed by semistructured telephone interview as Barthel-Index, modified Rankin scale and extended Barthel-Index. Five patients (mean age 67.2 +/- 6.1 years) died within 5.2 +/- 2.4 days (range 2-8 days) after the first symptoms due to herniation. Nine patients (mean age 63.1 +/- 7.1 years) died 141.0 +/- 92.5 days (range 40-343) after stroke onset due to internal complications. 16 patients survived (mean surviving time 2.1 +/- 1.5 years, mean age 54.1 +/- 11.4 years). Mortality was related to age and the number of risk factors/comorbidity, and functional outcome was dependent on the number of risk factors/comorbidity. Our small observational, retrospective study suggests that hemicraniectomy in patients with space occupying MCA-infarction decreases mortality rate and increases functional outcome. Further randomized trials may prove useful to better define the indications, timing and prognosis for this procedure.