Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes.

BACKGROUND: Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. METHODS: To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. RESULTS: Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. CONCLUSION: We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.

[Diagnosis and treatment of status epilepticus in the intensive care unit]. / Diagnose und Behandlung des Status epilepticus auf der Intensivstation.

Both convulsive and nonconvulsive status epilepticus are associated with a high risk of morbidity and mortality. To limit brain damage, emergency investigation of etiology and treatment must be done synchronously. This review presents the general rules for treatment. The steps of pharmacologic escalation with benzodiazepines, antiepileptics, and anesthetics are discussed together with their advantages and disadvantages.

[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]. / Nicht-invasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

[Large left ventricular aneurysm after silent myocardial infarction. Documentation by serial non-invasive imaging]. / Grosses linksventrikuläres Aneurysma nach stummem Myokardinfarkt. Dokumentation mittels serieller nicht-invasiver Bildgebung.

HISTORY AND CLINICAL FINDINGS: A 60-year-old man had a workup for atypical angina. Noninvasive investigations, including computed tomography, showed no evidence for coronary artery disease. A few months later the patient was hospitalized because of severe epileptic seizures. Thyrotoxicosis was diagnosed and emergency thyroidectomy was performed. Two months after discharge the patient was again referred because of exercise-induced angina pectoris. INVESTIGATIONS AND DIAGNOSIS: Echocardiography and cardiac magnetic resonance imaging (MRI) showed a large aneurysm of the lateral wall of the left ventricle with a thrombus adhering to the wall. Coronary angiography and levocardiography confirmed the aneurysm and detected an occlusion of the distal part of the circumflex artery. TREATMENT AND COURSE: Surgical aneurysm resection with thrombectomy and endoventricular circular plasty (Dor procedure) was performed without postoperative complications. Six months after surgery the patient was in good general condition without any angina. Follow-up echocardiography as well as cardiac MRI gave proof of an excellent postoperative result. CONCLUSIONS: Noninvasive preoperative diagnosis and documentation as well as postoperative monitoring with modern imaging modalities, such as echocardiography and MRI are of great value in patients with left ventricular aneurysm.

CT perfusion predicts secondary cerebral infarction after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To prospectively assess the diagnostic accuracy of CT perfusion (CTP) and transcranial Doppler sonography (TCD) for the prediction of secondary cerebral infarction (SCI) after aneurysmal subarachnoid hemorrhage (SAH). METHODS: During 2 weeks after SAH, 38 consecutive patients completed an average of 3.5 CT/CTP and 10.7 TCD examinations at regular intervals as required by the study protocol. SCI was defined as delayed infarction on native CT between 3 and 14 days after SAH and developed in n = 14 patients (n = 24 without SCI). Analysis was based on examination dates before SCI. Common measures of diagnostic accuracy were calculated for qualitative CTP (visual color-map ratings from two blinded observers) and TCD assessments (mean flow velocity >120 cm/s in anterior, middle, and posterior cerebral artery territories). Quantitative measures, which for CTP were obtained from cortical a priori regions of interest corresponding to the vascular territories, were analyzed by binary logistic regression. RESULTS: Time of prediction for SCI by CTP was at a median of 3 days (range 2 to 5 days) before manifestation of complete infarction on native CT. Visual assessment of time-to-peak (TTP) color maps performed best for the prediction of SCI with 0.93 sensitivity (95% CI: 0.7 to 1.0) and 0.67 specificity (95% CI: 0.53 to 0.7). On quantitative analysis, the odds ratio (OR) for 1 second of side-to-side delay in TTP was 1.4 (p = 0.01, Wald chi(2) = 8.57, CI: 1.07 to 1.82). Daily TCD measures were not significantly related to SCI at any time before complete infarction on native CT. CONCLUSIONS: Time to peak as indicated by CT perfusion is a sensitive and early predictor of secondary cerebral infarction.

Genetic risk factors in young adults with 'cryptogenic' ischemic cerebrovascular disease.

Mutations such as factor V Leiden G1691A (FVL), prothrombin G20210A (FIIM), methylenetetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthase (CBS) 844ins68 and endothelial cell protein C receptor (EPCR) 4031ins23 are risk factors for thromboembolism. To assess the role of these mutations in young adults with cerebral ischemia of otherwise undetermined etiology, 93 patients younger than 50 years old with thromboembolic strokes or transient ischemic attacks were studied. One hundred and eighty-six healthy age-matched and sex-matched blood donors served as controls. The FVL mutation was detected in 15/93 patients and 13/186 controls. After adjustment for smoking, arterial hypertension, and hyperlipidemia, the association of the FVL mutation with cerebral ischemia [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.38-7.39] remained significant. One of 93 patients and 6/186 controls were carriers of FIIM (OR, 0.33; 95% CI, 0.04-2.75). We detected the MTHFR TT677 genotype in 9/93 patients and 26/186 controls (OR, 0.66; 95% CI, 0.30-1.47), a CBS 844ins68 mutation in 12/93 patients and 19/186 controls (OR, 1.30; 95% CI, 0.60-2.81), and an EPCR 4031ins23 mutation in 1/93 patients and in no control individual (P = 0.33). In conclusion, in younger adults the FVL mutation is a risk factor for cerebrovascular disease. FIIM, the MTHFR TT677 genotype and the CBS 844ins68 mutation did not contribute to the risk in this group of patients. The EPCR 4031ins23 mutation is very rare, its possible role needs further investigation.

Psychotic symptoms and emotional distress in patients with Guillain-Barré syndrome.

Psychological disturbances in 49 most severely compromised Guillain-Barré syndrome patients were prospectively studied by a semistructured interview and assessed by repeat psychiatric examination during the patients' stay in the neuro-intensive care unit (ICU). Additional information was obtained from attending physicians, nurses and relatives. Anxiety (82%), acute stress disorder, depressive episodes (67%) and brief reactive psychosis (25%) were observed, with oneiroid psychosis (14%) among the latter. Psychotic episodes were strongly associated (p < 0.001) with severe tetraparesis, artificial ventilation and multiple cranial nerve dysfunction. CSF protein concentration was also correlated with the occurrence of psychotic symptoms. Patients themselves experienced loss of communication to be the most difficult condition to cope with. Fifty-five percent explicitly felt reassured by the environment of the ICU and 90% described contact with relatives to be most helpful. Our data suggest that motor deprivation and loss of communication are the conditions most closely connected with the occurrence of psychotic symptoms. Therapeutically, continuous psychosocial support and psychopharmacological measures may both be valuable tools to ameliorate distress.

[Customary use of compression stockings for prevention of thrombosis in medical intensive care units in Germany]. / Praxis medizinischer Thromboseprophylaxestrümpfe auf konservativen Intensivstationen in Deutschland.

BACKGROUND: Stockings for thrombosis prophylaxis (MTS) are generally advised for all immobilized patients by the German Societies of Surgery, Orthopedics, and Phlebology. In critical care patients, the indication is unclear and many questions are left unanswered, especially if combined with heparins for prophylaxis of thromboembolism. We evaluated the customary use of MTS in critical care patients. METHODS: A multiple choice questionnaire was sent to the nursing staff of 324 randomly selected German non-surgical ICUs. The answers of 144 units (44.4%) could be evaluated, 15 of which were special neurology, 88 special internal medicine, 41 mixed. RESULTS: Each 8th ICU principally avoids MTS, each 19th ICU principally provides all patients with MTS. Of those who use special indications, the degree of immobilisation plays an indecisive role with 50% for and 50% against MTS. In particular, coma serves as a contraindication. Effective anticoagulation excludes the need for MTS in half of the ICUs. Polyneuropathies and dysesthesias are the far most noticed arguments against MTS. CONCLUSIONS: There seems to be an uncertainty about the indication of MTS for non-surgical critical ill patients. With respect to available guidelines, a decision in principle for MTS should be made. However, in the individual patient with relative contraindications and progressively effective anticoagulation, MTS may be dispended relatively liberally.

Brain microembolic counts during extracorporeal circulation depend on aortic cannula position.

Thrombofibrinous and gaseous brain microemboli are commonly observed during extracorporeal circulation in patients undergoing cardiac surgery. Recent studies showed a preference of microemboli to the left hemisphere. We hypothesized that placement of the aortic cannula tip within the aorta descendens rather than in the aorta ascendens as commonly used reduces the number of microemboli to the brain and also reduces the side preference. Of 60 patients undergoing elective coronary artery bypass grafting primarily randomized to either a short aortic cannula (aorta ascendens) or an elongated one (aorta descendens), 29 (16 and 13) patients had complete and technically perfect continuous intraoperative transcranial Doppler sonography with embolus detection bilaterally. The number of high-intensity transient signals (HITS) was 994 +/- 2118 (mean +/- SD) for the short cannula group and was significantly lower with the elongated cannula (223 +/- 208; p < 0.02). HITS counts per min also differed significantly in favour of the aorta descendens group (p < 0.02), but there was an overlap. Thus, elongated cannulas can reduce, but not prevent microembolism to the brain. The side-to-side ratio of microemboli revealed more events in the left hemisphere, but this was similar in both groups. This suggests that individual anatomic factors may be responsible for this hemodynamically-mediated effect.

Detection of serious bradyarrhythmias in Guillain-Barré syndrome: sensitivity and specificity of the 24-hour heart rate power spectrum.

This study was undertaken to determine the nature of bradyarrhythmic events and their relationship to motor disability, disease stages and tachycardia in patients with Guillain-Barré syndrome, and to investigate the potential of the 24-hour heart rate power spectrum (HRPS) for the detection of serious bradyarrhythmias in individual patients. Thirty-five consecutive patients with Guillain-Barré syndrome who were admitted to the authors' intensive care unit were studied. In all patients, the heart rate was continuously recorded during the early stages of the disease, averaged at 1-minute intervals, and stored for 1 to 87 days. The HRPS (n = 556, 16 +/- 19 per patient; median, 9) was calculated by Fourier analysis of 24-hour recordings and logarithmically transformed. The slope was estimated by regression analysis of log (power) on log (frequency) between 10(-4) and 4 x 10(-3) Hz, showing an inverse power law behavior in all 556 HRPSs. Eleven patients (31%) had serious bradyarrhythmias. Most of these patients were not dependent on mechanical ventilation, with 3 of 11 patients (27%) still being able to walk more than 5 meters. Sustained tachycardia occurred less frequently in patients with than in those without bradyarrhythmias. The combination of the slope of the power law regression line and the log (power) at 10(-4) Hz (log P4) of the 24-hour HRPS correctly identified 8 of 11 bradyarrhythmic patients (sensitivity 73%) and 16 of 22 patients with Guillain-Barré syndrome who did not have bradyarrhythmias (specificity 73%). All bradyarrhythmic patients could be detected in the subgroup of patients without sustained tachycardia. The 24-hour HRPS is a powerful predictor of serious autonomic complications in patients with Guillain-Barré syndrome and may help to identify patients at risk of potentially life-threatening arrhythmias.

Early natural course of transient encephalopathy after coronary artery bypass grafting.

OBJECTIVE: A decline of neuropsychological performance is an unwanted side effect of coronary artery bypass grafting (CABG) with extracorporeal circulation. There is little data on the neuropsychological changes during the first 2 wks after CABG. DESIGN, SETTING, PATIENTS: In this prospective observational study at our university medical center, a group of 67 patients who underwent routine CABG was selected for absence of comorbidity (such as carotid stenosis, previous stroke, dementia, and advanced general medical disorders) and examined. In this selected group of patients, no focal deficit was seen throughout the study. A total of 20 hospitalized patients with different types of peripheral neuropathy and free from drugs interfering with cognition served as a control group for the practice effects of the neuropsychological testing. MEASUREMENTS AND MAIN RESULTS: Seven standard tests covering different neuropsychological domains were used as a composite battery. Examinations took place before surgery and serially at days 3, 6, and 9 after CABG; general neurologic examination was done every day, including the first postoperative day. We observed a definite decline in all tests at day 3 (p < .01) and progressive recovery thereafter up to or even beyond preoperative values within 9 days (p < .01). Transient depression as indicated by self-rated scores occurred in some patients. CONCLUSION: We observed a uniform, but transient, deterioration in performance on a battery of frequently repeated standardized neuropsychological tests early after CABG. Our data on the early natural course may help to better evaluate treatment efforts aimed at preventing or reducing after-surgery neuropsychological alterations.

Cerebral microembolus generation in different extracorporeal circulation systems.

Microemboli generated during extracorporeal circulation (ECC) are likely to induce neurological sequelae. This study examines whether the choice of a distinct type of ECC can reduce intracerebral emboli counts. Middle cerebral artery blood flow during coronary artery bypass grafting was monitored continuously by transcranial Doppler ultrasound in 45 patients. The ECC systems used were a roller pump (n = 16), a centrifugal pump (n = 18) and a combination of centrifugal pump and heparin-coated ECC system (n = 11). Patients' characteristics as well as surgical and anesthesiological procedure did not differ between the groups. Total counts did not differ significantly between the three groups. Intraoperative events in individual patients may lead to massive embolus generation overcoming positive properties of a distinct ECC system.

Intraoperative embolus formation during cardiopulmonary bypass affects the release of S100B.

BACKGROUND: Intraoperative thromboembolism and the systemic inflammatory reaction are thought to play a role in causing cerebral dysfunction following cardiopulmonary bypass (CPB). Increased levels of S100B, an astroglial protein, have been linked to neuropsychological deficits after CPB. The present study investigated whether S100B release correlates with intraoperative embolus formation, thrombin formation, or the release of inflammatory parameters. METHODS: 40 patients undergoing coronary artery bypass grafting were included. Blood samples were taken before, during, and after CPB, and levels of S100B, thrombin-antithrombin complex (TAT), complement C5a, and interleukin 8 were analysed. Embolus formation was assessed by Doppler ultrasound at the arterial line of CPB. RESULTS: The release of S100B correlated with embolus count (r = 0.42; p = 0.009) and TAT formation (r = 0.71; p = 0.0001). The correlation of S100B with interleukin 8 (r = 0.58; p = 0.0001) was due to the dependence of both parameters on bypass time (r = 0.29; p = 0.075, partial correlation). A correlation of S100B with C5a formation could not be observed. CONCLUSIONS: S100B release is related to embolus and thrombin formation during CPB, indicating that thrombofibrinous embolism is involved in perioperative brain damage. Inflammatory parameters (i.e. interleukin 8 and C5a) seem to have no influence on S100B release.

Bilateral cerebral emboli monitoring during extracorporeal circulation.

Microembolism generated during extracorporeal circulation is thought to be responsible for stroke and neuropsychological deficits. Before one can investigate the pathogenetic role in more detail, reproducible and reliable quantitative methods need to be developed. In several previous studies, microemboli detection was performed unilaterally. We questioned if this reflects the bihemispheric embolic load. In 42 patients undergoing coronary artery bypass grafting, bilateral embolus detection was performed during extracorporeal circulation. The side-to-side correlation of microembolus counts was strong (0.91), but there was a significant difference in number (p < 0.01) comparing left and right emboli. The side of higher embolus counts cannot be predicted in the individual because either side may show higher counts. Doubling the unilateral count may deviate from the bilateral count by as much as 51% in the individual patient. The total embolic load to the brain during extracorporeal circulation cannot be precisely predicted from unilateral transcranial insonation alone.

Cerebral arteriovenous transit time (CTT): a sonographic assessment of cerebral microcirculation using ultrasound contrast agents.

Transcranial color-coded sonography (TCCS) has been used to investigate major brain-supplying arteries, draining veins and brain parenchyma. Here, we describe a contrast-enhanced TCCS analysis of cerebral arteriovenous transit time (cTT) as a measure of cerebral microcirculation. We evaluate its reproducibility and its correlation with clinical impairment of brain function and neuropsychological tests. A total of 27 patients with cerebral microangiopathy and 30 healthy controls were examined. CTT is defined by the time an ultrasound contrast agent requires to pass from the P2-segment of the posterior cerebral artery to the vein of Galen. This was measured by comparison of power Doppler intensity in two off-line defined regions of interest. Serial intraindividual cTT measurements within several min showed a good reproducibility of this parameter. cTT was significantly longer in patients with cerebral microangiopathy than in controls (Mann-Whitney U test,p < 0.001) and related to cognitive impairment measured by the Mini-Mental-State examination. We conclude that it is a quick and reliable parameter related to increased vascular resistance of the microcirculation or a rarefaction of microvessels. Further studies are needed to show the sensitivity and specificity of cTT in the diagnosis of small vessel disease and the interference of important circulation factors, such as heart failure or blood viscosity.

Diagnosis of MCA-occlusion and monitoring of systemic thrombolytic therapy with contrast enhanced transcranial duplex-sonography.

A case of a successful systemic thrombolysis of an acute middle carotid artery occlusion is reported. The case underlines the role of contrast-enhanced transcranial color-coded duplex sonography as a noninvasive technique for rapid diagnosis of vessel occlusion in acute stroke. The diagnostic potential of transcranial color-coded duplex sonography for indication and monitoring of intravenous systemic thrombolytic therapy is demonstrated.

Primary intracerebral Hodgkin's disease: report of a case with Epstein-Barr virus association and review of the literature.

A case of primary intracerebral Hodgkin's disease (HD) without dural attachment in a 54-year-old immunocompetent patient is described. The infiltrate was located superficially in the occipital lobe and corresponded to the histologic type of nodular sclerosis. A typical immunohistochemical profile (membrane and cytoplasmic staining with dotlike Golgi enhancement of CD30, moderate cytoplasmic staining of CD15 in the Golgi area, membrane staining of CD20 of <10% of blastic cells, CD45RB negative) and in addition Epstein-Barr virus (EBV) latent membrane protein was detectable in Reed-Sternberg cells. Staging revealed no other organ sites of involvement. After combined surgery, postoperative radiotherapy, and chemotherapy, there are no signs of recurrence or systemic disease on follow-up for >1 year. To the authors' best knowledge, an association of EBV with primary central nervous system HD has not been demonstrated before.