Systemic thrombolysis with rt-PA in patients under 40 years of age: a subgroup analysis of the Cologne Stroke Experience.

BACKGROUND: While the application of intravenous systemic thrombolysis (IVT) with rt-PA (recombinant tissue plasminogen activator) in older patients is currently moving into the focus of epidemiological studies, only few data are available regarding the application in young patients ≤40 years. Single-center data of a thrombolysis register were analyzed with respect to safety and efficacy of the treatment of young patients. METHODS: In a retrospective subgroup analysis of 450 patients treated by IVT within a 3-hour time window, patients ≤40 years were identified (n = 20). Clinical data [age, pretherapeutic stroke severity (National Institute of Health Stroke Scale, NIHSS), OTT (onset to-treatment time), rt-PA-dose, DNT (door[-]to[-]needle time), rate of symptomatic intracranial hemorrhages] and medical history were determined. The clinical outcome was assessed by the mRS (modified Rankin Scale). The results were compared to those of patients >40 years (n = 430). RESULTS: Twenty patients ≤40 years (mean age 32 years) out of 450 patients (4%) were treated by IVT. The percentage of predisposing diseases and vascular risk factors was significantly lower when compared to patients >40 years (p < 0.05). In contrast, the percentage of smokers was significantly higher (55 vs. 24%; p < 0.05). In comparison to patients >40 years, OTT, DNT and NIHSS at admission were not significantly different. After 3 months, 11 of 20 young patients (55%) showed a favorable outcome (mRS 0-1) and 80% were functionally independent (mRS 0-2). In the group of patients >40 years (n = 430), the respective percentages were significantly lower [p < 0.05; 34% (mRS 0-1) and 52% (mRS 0-2), respectively]. Symptomatic intracranial hemorrhages were not observed (in patients >40 years: 4%, p < 0.05). CONCLUSIONS: In comparison to the cohort of patients >40 years, IVT in young patients is safe and leads to a significantly better outcome after 3 months. Our data therefore encourage the use of IVT in young patients.

A giant bilateral calcified chronic subdural hematoma.

BACKGROUND: A calcified chronic subdural hematoma is a rare disease and its neuroradiological presentation is variable. The degree of calcification extends from thin calcified inner membranes to dense calcification and even ossification of the hematoma. Previous reports described a maximum of two hematoma cavities with calcified inner hematoma membranes. METHODS: Neuroimaging report with illustrative computerized tomography images. RESULTS: A patient with a bilateral symptomatic calcified chronic subdural hematoma, or so-called "armoured brain", was admitted to our intensive care unit with clinical signs of increased intracranial pressure. Computerized cranial tomography demonstrated multiple bilaterally located hematoma cavities with thin calcified inner membranes. After neurosurgical intervention by bilateral burr hole trepanation, clinical symptoms improved. CONCLUSIONS: Our case of a calcified chronic subdural hematoma presents with an uncommon imaging pattern with more than four hematoma cavities bounded by predominantly convex- and concave-configured thin calcified inner membranes.

Selective immune adsorption treatment of severe Guillain Barré syndrome in the intensive care unit.

BACKGROUND: The effectiveness of plasma exchange and intravenous application of immunoglobulins (IVIG) for the treatment of the Guillain Barré syndrome (GBS) has been demonstrated in large collectives. In contrast, there are only a few investigations in GBS patients with severe symptoms admitted to the intensive care unit (ICU) and treated with selective immune adsorption (SIA). We compared the efficacy and safety of SIA only versus SIA followed by IVIG in patients with severe GBS. METHODS: Patients with severe GBS admitted to the ICU were treated with SIA only or in combination with IVIG. Severity of symptoms was assessed using Hughes grades and severe GBS was defined as ≥ 3. Data were acquired retrospectively for the last 10 years (1998-2008). RESULTS: Data from 30 GBS patients (age 53 ± 16 years) with severe symptoms (Hughes grade 5: 30% [n = 9], grade 4: 57% [n = 17], grade 3: 13% [n = 4]) were analyzed. The mean Hughes grade at admission was 4.2 ± 0.7. Ten patients were treated by SIA only, 20 patients were treated sequentially with SIA followed by IVIG (30 g/d) over 3 days. The number of SIA sessions was 3.2 ± 0.8. Improvement of Hughes grade 4.2 ± 0.7 to 3.4 ± 0.9 (P < 0.001) occurred within 14.6 ± 15.5 days. Treatment with SIA only was as effective as the sequential therapy with IVIG. The Hughes grade decreased significantly in the group of patients where SIA was performed only (P = 0.008) and in the sequential treatment group (P < 0.001), respectively. In one patient SIA had to be terminated after one session due to ICU complications. Other severe side effects were not observed. CONCLUSIONS: In severely affected GBS patients admitted to ICU treatment with SIA seems to be safe and effective. In comparison to treatment with SIA only, sequential therapy with IVIG was not more effective.

Which time-to-peak threshold best identifies penumbral flow? A comparison of perfusion-weighted magnetic resonance imaging and positron emission tomography in acute ischemic stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, the hypoperfused but viable tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP) maps are frequently used to estimate the hemodynamic compromise and to calculate the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral flow by comparison with positron emission tomography (PET). METHODS: Magnetic resonance imaging (MRI) and PET were performed in 11 patients with acute ischemic stroke (median 8 hours after stroke onset, 60 minutes between MRI and PET imaging). The volumes defined by increasing TTP thresholds (relative TTP delay of >2, >4, >6, >8, and >10 seconds) were compared with the volume of hypoperfusion (<20 mL/100 g per min) assessed by 15O-water PET. In a volumetric analysis, each threshold's sensitivity, specificity, and predictive values were calculated. RESULTS: The median hypoperfusion volume was 34.5 cm3. Low TTP thresholds included large parts of the hypoperfused but also large parts of normoperfused tissue (median sensitivity/specificity: 93%/60% for TTP >2) and vice versa (50%/91% for TTP >10). TTP >4 seconds best identifies hypoperfusion (84%/77%). The positive predictive values increased with the size of hypoperfusion. CONCLUSIONS: This first comparison of quantitative PET-CBF with TTP maps in acute ischemic human stroke indicates that the TTP threshold is crucial to reliably identify the tissue at risk; TTP >4 seconds best identifies penumbral flow; and TTP maps overestimate the extent of true hemodynamic compromise depending on the size of ischemia. Only if methodological restrictions are kept in mind, relative TTP maps are suitable to estimate the mismatch volume.

Predictive value of neurochemical monitoring in large middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke. Early identification of patients at risk is necessary to decide on invasive therapies such as decompressive hemicraniectomy or hypothermia. To assess potential predictors of malignant brain edema by measurement of intracranial pressure (ICP) and microdialysis in patients with large hemispheric stroke and different clinical course. METHODS: In an ongoing prospective clinical study, an ICP and microdialysis probe were placed into the parenchyma of the ipsilateral frontal lobe of 10 patients. Extracellular concentrations of glutamate, lactate, pyruvate, and glycerol were measured continuously. Repeated cranial CT scans were scrutinized for size of infarction and presence of mass effect. RESULTS: The dynamics of the different substances varied in accordance with the clinical course, size of infarction, and local brain edema: Increase in ICP and in glutamate concentration and lactate-pyruvate ratio was followed by massive edema and large infarcts; generally low and stable ICP and substrate concentrations were found in patients without progressive space-occupying infarcts. CONCLUSIONS: In patients with large hemispheric infarction, bedside monitoring with microdialysis is feasible and might be helpful together with ICP recording to follow the development of malignant brain edema.

Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography.

In a randomized double-blind placebo-controlled study of 27 patients with acute ischemic stroke, the effect on regional CMRglc (rCMRglc) of the calcium channel blocking agent nimodipine administered in addition to routine treatment was investigated. Following computed tomography-supported diagnosis of focal ischemia in the middle cerebral artery territory, positron emission tomography (PET) of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was performed, and the patients were entered into the study within 48 h after onset of symptoms, randomly receiving either nimodipine (2 mg/h constant i.v. infusion for 5 days, 120 mg/day orally for another 16 days) or carrier/placebo. FDG PET was repeated after completion of therapy. The clinical course was followed during the treatment period and for 6 months after the stroke, using the Mathew Score for early and the Barthel Index for late assessment. During that observation period, five patients died in the nimodipine group and four in the control group. Subsequently, the code was broken, and the clinical and PET data were analyzed in relation to treatment assignment, with the nimodipine group comprising 11 and the control group 12 eligible cases. The two groups were similar with respect to age and sex distribution, initial clinical deficit, and infarct size and location. While the infarct rCMRglc showed comparable slight increases over time in both groups, the metabolic changes in the other evaluated regions (contralateral infarct mirror region, ipsi- and contralateral cerebral gray matter, contra- and ipsilateral cerebellar hemispheres) differed significantly between treatment groups (side x region x treatment interaction p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of propentofylline on regional cerebral glucose metabolism in acute ischemic stroke.

In a randomized double-blind placebo-controlled study in 30 patients with acute ischemic stroke, the effect of the adenosine uptake blocker propentofylline on regional brain glucose metabolism (rCMRglu) was investigated using repeated positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Treatment was initiated within 48 h after onset of symptoms. The clinical course was followed for 3 months. In the propentofylline group, after 14 days rCMRglu was increased in the infarct by 37.3% and was practically unchanged in other brain regions, whereas in the control group glucose metabolism had decreased in all regions (1.4-13.4%). These differences were significant between the two groups [Analysis of variance (ANOVA) p = 0.005]. Although there was a trend toward greater clinical improvement in the propentofylline-treated patients, this did not reach statistical significance. The results correspond to experimental data showing that propentofylline improves energy metabolism in cerebral ischemia. A clinical trial is needed to determine whether this new therapeutic principle can be successfully used in acute human stroke.

Early intravenous thrombolysis with recombinant tissue-type plasminogen activator in vertebrobasilar ischemic stroke.

BACKGROUND: The optimal therapy of vertebrobasilar ischemic stroke is under debate. In the case of underlying basilar artery occlusion, intra-arterial thrombolysis is recommended. Because this pathologic condition is rarely found and the procedure is time consuming and restricted to specialized centers, the question arises whether early intravenous thrombolysis could also effectively be applied in vertebrobasilar ischemic stroke. OBJECTIVE: To determine if early intravenous thrombolysis could be used effectively in vertebrobasilar ischemic stroke. DESIGN: A case series of 12 consecutive patients with acute vertebrobasilar ischemia were followed up 3 months after thrombolytic treatment at the Department of Neurology of the University Hospital of Cologne, Cologne, Germany, a primary care and referral center. METHODS: Patients with clinically diagnosed moderate to severe vertebrobasilar ischemic stroke with clearly determined symptom onset were treated with intravenous recombinant tissue-type plasminogen activator within 3 hours after symptom onset following a protocol similar to that of the National Institute of Neurological Disorders and Stroke study. RESULTS: On admission, 7 patients exhibited moderate to severe brainstem symptoms without impairment of consciousness and 5 patients had impairment of consciousness, of whom 2 were comatose. Of 12 patients, 10 had a favorable outcome after 3 months defined as full independence (Barthel index score of 100) or return to premorbid condition. One patient had a poor outcome with complete dependency due to reocclusion after primarily successful thrombolysis, and 1 patient died of severe brainstem infarction and additional space occupying parietal hemorrhage. CONCLUSION: Favorable outcome could be achieved in the majority of 12 consecutive patients with moderate to severe vertebrobasilar ischemic stroke treated with intravenous recombinant tissue-type plasminogen activator within 3 hours after symptom onset.

Early diagnosis and successful treatment of acute cytomegalovirus encephalitis in a renal transplant recipient.

We report the case of a 40-year-old male HIV-negative renal transplant patient with allograft rejection and immunosuppressive therapy who presented with acute cytomegalovirus (CMV) encephalitis. CT and MRI of the brain were normal but EEG showed diffuse slowing and dysrhythmia. In cerebrospinal fluid (CSF) initially 81 cells/microliters were found and immunocytochemistry showed a decreased CD4/CD8 ratio and increased values of activated lymphocytes, natural killer cells and immunoglobulin-containing cells. CMV-specific IgM antibodies in CSF and serum, immunostaining of CMV antigen in CSF cells and virus culture from CSF and urine were negative. During the first 3 weeks of illness no intrathecal production of immunoglobulins could be detected. Early diagnosis of CMV encephalitis was made by in situ hybridization (ISH) on CSF cell preparations and the polymerase chain reaction (PCR) which was positive in CSF and blood. On day 26 diagnosis was confirmed by detection of CMV-specific intrathecal IgG production. The patient was treated with ganciclovir, anti-CMV immunoglobulins and intrathecal beta interferon. He recovered completely after 2 months. Our data demonstrate the usefulness of ISH and PCR in the early diagnosis of CMV encephalitis and perhaps may encourage the use of intrathecal beta interferon in other patients with this disease.

MRI- and MRA-guided therapy of carotid and vertebral artery dissections.

A high sensitivity and specificity has been shown for magnetic resonance imaging (MRI) and angiography (MRA) in the diagnosis of internal carotid (ICAD) and vertebral (VAD) artery dissections, where arteriography has been and still is the gold standard. Five patients (three with ICAD, two with VAD; age range 42-56 years) are presented, in whom diagnosis and follow-up management were exclusively based on non-invasive measures. In all patients, MRI demonstrated a typical intramural hematoma and MRA in 3D phase contrast technique showed loss or diminished flow. After anticoagulation (heparin) for 3 to 4 weeks follow-up, MRI showed a regression of the mural hematoma and MRA revealed reperfusion or improvement of flow. Depending on the extent of MRI-/MRA-pathology, three patients were put on antiplatelet therapy and two on Coumadin until normalization of MRI and MRA findings, which are assessed in 3-months intervals. We suggest, that with, (I) a suspicious history, symptoms and signs for cervical artery dissection (CAD), (II) typical MR-findings proven to indicate CAD, (III) improving or resolving at follow-up, (IV) in unusual location for atherosclerotic involvement, (V) in the absence of coexisting atherosclerotic lesions, the diagnosis has not to be confirmed with conventional arteriography. Therefore, safe MRI- and MRA-guided anticoagulation and antiplatelet therapy during serial follow-up measurements are possible.

Catatony in Graves' disease.

We report a 27-year-old female patient with prior history of Graves' disease and relapsing episodes of tachycardia, hyperpyrexia, muscular rigidity and coma. With the subsequent manifestation of an acute schizophreniform psychotic disorder unresponsive to neuroleptics, the primary syndrome was re-classified as febrile catatony. Hyperthyroidism was ruled out with normal serum thyroid hormone levels, as were toxic effects of thyrostatic treatment, drug-induced hypothyroidism and a malignant neuroleptic syndrome. All psychiatric symptoms subsided completely following subtotal thyroidectomy. Febrile catatatony has to be added to the spectrum of psychotic phenomena that may be caused by Graves' disease, irrespective of serum thyroid hormone levels.

[Hypokalemic paralysis in furosemide therapy and simultaneous laxative abuse]. / Dyskaliämische Lähmung bei Furosemidtherapie und gleichzeitigem Laxanzienabusus.

BACKGROUND: Clinical signs of hypokalemia are not directly related to the extent of the electrolyte imbalance, and therefore monosymptomatic cases may be observed. CASE REPORT: Following an acute gastroenteritis with considerable diarrhea, a 47-year-old male patient was admitted to hospital for progressive painful paraparesis. Upon admission, the patient complained of painful paresthesias in both legs, and a moderate flaccid paraparesis with widespread fasciculations and loss of leg tendon reflexes was found. Serum potassium level on admission was 1.7 mmol/l. Other signs of hypokalemia were absent, and the ECGs showed a slow sinus rhythm without disturbances of de- or repolarisation or cardiac arrhythmias. Hypokalemic paralysis was diagnosed and was considered to be primarily drug-induced, as the patient had a history of laxative abuse and was on a continuous medication with furosemide (80 mg/d) without regular assessment of serum electrolytes. The additional electrolyte loss following the gastroenteritis precipitated the development of clinical signs of hypokalemia. In parallel to the rise in serum potassium levels, both painful paresthesias and muscle weakness disappeared, and electromyography documented the amelioration of the myopathic syndrome. CONCLUSION: The prominent clinical symptom of hypokalemia was a dyskalemic paralysis in the absence of other sequelae of electrolyte imbalance, such as cardiac arrhythmias or vegetative disturbances.

Primary stroke unit treatment followed by very early carotid endarterectomy for carotid artery stenosis after acute stroke.

BACKGROUND: Although it is recognized that carotid endarterectomy (CEA) is the treatment of choice in symptomatic internal carotid artery (ICA) stenosis, in the past, very early CEA has been shown to carry substantial risks. We assessed an interdisciplinary concept of very early CEA in patients with high-grade (>70%) symptomatic ICA stenosis at a single center. PATIENTS AND METHODS: The course of treatment and outcomes of patients who underwent CEA as early as possible after being referred to the stroke unit for symptoms of transient ischemic attack and stroke were prospectively evaluated, including the following parameters: age, severity of ischemia-related symptoms according to the modified Rankin scale, duration of symptoms until admission, multimodal imaging findings (color-coded duplex, cranial computed tomography, magnetic resonance imaging, positron emission tomography), duration until CEA, perioperative course and complications, as well as duration of in-hospital care. RESULTS: Fifty consecutive patients (median age 68 years, range 44-90) with clinical and imaging signs of transient ischemic attack (n = 19) or stroke (n = 31) were included from January 2000 until December 2004. All except 1 patient showed a preoperative Rankin < 4. There was a median time period of 6 h between the onset of symptoms and admission (range 1 h to 15 days) and a median duration of 4 days after admission until operation (range 1-21 days). Seven patients underwent CEA of the contralateral, severely stenosed ICA after symptomatic ipsilateral ICA occlusion. Four out of 5 patients who primarily underwent systemic thrombolysis recovered almost completely. Three patients (6%) experienced a clinical deterioration before surgery. In the majority of patients (43/50), CEA was performed under local anesthesia with selective shunt use which became necessary in 26%. Three patients (6%) had postoperative worsening due to new infarcts. In 2 cases, an intracerebral hemorrhage occurred, of which 1 remained asymptomatic. In 1 case, surgical revision was necessary because of an ICA thrombosis without permanent neurological decline. Patients were discharged after a median time of 14.5 days (range 4-44). CONCLUSIONS: After careful selection and preparation in a stroke unit, patients with acute stroke due to carotid stenosis can undergo very early CEA under local anesthesia with a perioperative risk comparable with the risk of later endarterectomy, therefore preventing very early stroke recurrences.

Autologous blood stem cell transplantation in refractory systemic lupus erythematodes with recurrent longitudinal myelitis and cerebral infarction.

Autologous hematopoietic stem cell transplantation (ASCT) has the potential to eliminate autoreactive lymphocytes and may represent a therapeutic option for patients with refractory autoimmune diseases. We describe a 19-year old woman with neuropsychiatric systemic lupus erythematodes (NPSLE) presenting with acute longitudinal myelitis and aseptic meningitis. Despite therapy with methylprednisolone and cyclophosphamide (CYC), recurrence of longitudinal myelitis and a disabling stroke-like relapse occurred. Hematopoietic stem cells were mobilized by CYC at 2 g/m2 and G-CSF. The patient was conditioned by CYC at 200 mg/kg and anti-thymocyte globulin and 3.6 x 10(6) CD34+ cells/kg were infused. Hematopoietic regeneration was observed on day 12 after ASCT. Currently, 18 months after ASCT, the patient is in clinical remission with no evidence for residual serological or neuroradiological activity of SLE. Although a longer follow-up will be needed to reliably assess the efficacy of ASCT in this patient, the present case demonstrates that ASCT may represent a therapeutic option for patients with severe NPSLE.

Clozapine-induced agranulocytosis and thrombopenia in a patient with dopaminergic psychosis.

In patients with Parkinson' disease and dopaminergic psychosis, clozapine treatment is recommended as the drug is free from extrapyramidal side effects and does not worsen motor symptoms of the underlying disease. The use of clozapine, however, is limited due to its hematotoxic side effects. For treatment of clozapine-induced agranulocytosis, granulocyte colony-stimulating factors (G-CSF) are recommended. We report the case of a 72-years-old male patient with clozapine-induced agranulocytosis and thrombopenia. Neutropenia was successfully treated with G-CSF, but thrombopenia persisted and resolved spontaneously after 14 days. Bone marrow toxicity of clozapine is not restricted to white cell maturation, but may also impair thrombocytopoesis.

[Protracted course of bromazepam poisoning in advanced age]. / Protrahiert verlaufende Bromazepam-Intoxikation im höheren Lebensalter.

HISTORY AND CLINICAL FINDINGS: A 68-year-old woman was found unconscious and hardly breathing. Artificial ventilation was undertaken by an emergency physician who brought her to hospital. Physical examination provided no evidence of relevant organ abnormalities. Neurological examination of the comatose patient revealed absent brain-stem reflexes and spontaneous respiration. But no other focal neurological abnormalities were found. INVESTIGATIONS: Routine laboratory tests, ECG, chest radiogram, Doppler sonography of arteries to the brain, lumbar cerebrospinal fluid and computed tomography of the skull were unremarkable. Toxicological tests discovered bromazepam intoxication (serum level 6 mg/l; maximal serum level after intake of 6 mg of the active constituent: 0.1 mg/dl). DIAGNOSIS, TREATMENT AND COURSE: When bromazepam poisoning was demonstrated elimination of the drug was no longer feasible; the spontaneous course of the poisoning with slowly falling drug levels could thus be observed over 10 days. In parallel with the fall of bromazepam concentration in blood, restitution of breathing and of brain-stem reflexes was recorded until, 12 days after intake of the drug, normal functions had been restored. CONCLUSION: Central respiratory arrest occurred at a bromazepam serum level of 6 mg/l. Without intensive medical care the patient would not have survived.