Karen Koopman

Improved discrimination of autopsy-confirmed Alzheimer's disease (AD) from non-AD dementias using CSF P-tau181P

To establish diagnostic accuracy (acc) and optimal cut-off levels of CSF tau phosphorylated at threonine 181 (P-tau(181P)) for discriminating Alzheimers disease (AD) from non-AD dementias in autopsy-confirmed dementia patients, CSF levels of beta-amyloid peptide (Abeta(1-42)), total tau protein (T-tau) and P-tau(181P) from patients with definite AD (n=95) and non-AD dementias (n=50) were determined with single-parameter ELISA kits. Optimal P-tau(181P) cut-off levels for differentiating AD from pooled non-AD dementias, dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) were 50.4pg/mL (acc=0.73), 52.8pg/mL (acc=0.73) and 35.3pg/mL (acc=0.90), respectively. The optimal CSF P-tau(181P) cut-off level for discriminating AD from non-AD dementias was 50.4pg/mL. Optimal CSF P-tau(181P) cut-off levels differed between non-AD diagnostic dementia categories.

Safety of antiplatelet therapy prior to intravenous thrombolysis in acute ischemic stroke

BACKGROUND There is some uncertainty whether prior use of antiplatelet (AP) drugs increases the risk of symptomatic intracerebral hemorrhage (SICH) and influences functional outcome in patients with ischemic stroke treated with intravenous thrombolysis. OBJECTIVE To assess whether prior use of AP drugs is related to outcome following intravenous tissue plasminogen activator therapy in patients with ischemic stroke. DESIGN, SETTING, AND PATIENTS A single-center prospective observational cohort study of the relation between prior AP therapy, occurrence of SICH, and functional outcome of consecutive patients with ischemic stroke undergoing intravenous thrombolysis with tissue plasminogen activator in a university hospital between April 1, 2002, and November 30, 2006. MAIN OUTCOME MEASURES The occurrence of SICH and favorable outcome reflecting independence defined as a modified Rankin Scale score of 2 or lower at 3 months. RESULTS Of the 301 patients who received intravenous tissue plasminogen activator, 89 used AP drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 12 patients (13.5%; 95% confidence interval, 7.8%-22.3%) who had received AP drugs and in 6 patients (2.8%; 95% confidence interval, 1.2%-6.2%) without prior AP therapy (P = .001). Multivariate analysis revealed that prior AP therapy was an independent predictor of SICH (odds ratio, 6.0; 95% confidence interval, 2.0-17.1). Nonetheless, prior AP therapy was independently associated with a favorable outcome (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). CONCLUSION Despite a higher incidence of SICH, the net benefit of intravenous tissue plasminogen activator therapy for acute ischemic stroke was greater in patients using AP drugs.

Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke

BackgroundLow cholesterol levels have been associated with an increased risk of haemorrhagic stroke. This study investigated whether lipid levels or prior statin use influence outcome in patients with acute ischaemic stroke treated with IV thrombolysis.MethodsThe relation between admission lipid levels or statin use and both the development of symptomatic intracerebral haemorrhage (sICH) and 3-months functional outcome was assessed in a prospective hospital-based stroke registry comprising 252 patients treated with IV tissue plasminogen activator (tPA). The fasting status of the patients was unknown. Favourable outcome at 3 months was defined as a modified Rankin scale score ≤ 2. Logistic regression analysis was performed with adjustment for possible confounders.ResultsLow density lipoprotein (LDL), total cholesterol levels, and statin use were not associated with sICH. Mean triglyceride levels were significantly higher (2.5 mmol/L vs 1.8 mmol/L, p = 0.02) and high density lipoprotein (HDL) was significantly lower (1.0 mmol/L vs 1.2 mmol/L, p = 0.03) in patients with sICH than in patients without sICH. Multivariable analysis showed that higher triglyceride levels were independently associated with sICH (OR 2.16 per mmol/ L increase, 95 % CI 1.20–3.91, p = 0.01). There was no relation between any of the lipid levels or statin use and functional outcome at 3 months.ConclusionsHigh admission triglyceride levels were independently associated with a higher risk of sICH, but were not associated with a reduced chance of a favourable functional outcome at 3 months. Total cholesterol levels, LDL levels and statin use had no influence on both the occurrence of sICH or functional outcome.

Statin Use and Functional Outcome after Tissue Plasminogen Activator Treatment in Acute Ischaemic Stroke

Background: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients prior on statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional outcome than statin-naïve patients. Methods: In a prospective observational cohort study of 476 acute ischaemic stroke patients treated with tPA we investigated the relationship between prior statin use and functional outcome at 3 months, the occurrence of symptomatic intracerebral haemorrhage (SICH) and early in-hospital mortality. Ischaemic stroke subtypes were defined according to the TOAST classification. Favourable outcome was defined as a modified Rankin Scale score ≤2. Results: Of the 476 patients included, 98 (20.6%) used a statin at stroke presentation. In the entire cohort, 45.6% of patients had a favourable outcome with no difference between patients with or without statin therapy (45.9 vs. 45.5%, p = 0.94). In the multivariable analysis, statin use was not associated with favourable outcome (OR = 1.1, 95% CI = 0.6–1.9, p = 0.87). In none of the different stroke subtype groups was statin use associated with favourable outcome. Finally, statin use was not an independent risk factor of SICH or of early in-hospital mortality. Conclusion: Prior statin therapy in patients with acute ischaemic stroke treated with tPA is not associated with a more favourable outcome, and this is independent of stroke subtype.

Pitfalls in the diagnosis of reversible cerebral vasoconstriction syndrome and primary angiitis of the central nervous system

A case of a 51‐year‐old woman with reversible cerebral vasoconstriction syndrome (RCVS) without an associative cause is reported. Initially the diagnosis primary angiitis of the central nervous system (PACNS) was considered. Both diagnosis are rare and can mimic each other. Distinction between both can be difficult, but is necessary because of different treatment options. Clinical features and diagnostic assessments to distinguish RCVS from PACNS and the potential pitfalls are discussed.

An often unrecognized cause of thunderclap headache: reversible cerebral vasoconstriction syndrome

Thunderclap headache (TCH) can have several causes of which subarachnoid hemorrhage (SAH) is most common and well known. A rare cause of TCH is the reversible cerebral vasoconstriction syndrome (RCVS) which is characterized by a reversible segmental vasoconstriction of the intracranial vessels. We describe two patients with TCH due to RCVS and the probable precipitating factor, namely, cannabis and an anti-migraine drug. In RCVS, cerebrospinal fluid examination is (near) normal, in contrast to SAH and (primary) cerebral vasculitis. Brain MRI may be normal or shows infarction. MRA can demonstrate vasoconstriction of the great arteries, but a normal MRA does not rule out the diagnosis. Caliber changes on cerebral angiography cannot adequately differentiate between RCVS and vasculitis. Calcium-channel antagonists may be a good therapy and repeated transcranial Doppler ultrasonography can be a reliable non-invasive investigation to monitor the effect of treatment and demonstrate reversibility of the vasoconstriction.

Hyperdense middle cerebral artery sign and outcome after intravenous thrombolysis for acute ischemic stroke

BACKGROUND The presence of a hyperdense middle cerebral artery sign (HMCAS) on baseline brain CT is associated with poor clinical outcome in stroke patients treated with intravenous recombinant tissue plasminogen activator (tPA). It remains uncertain whether the presence of HMCAS is associated with acute neurological deterioration after tPA treatment. OBJECTIVE To evaluate the effect of HMCAS in routinely intravenous tPA-treated patients with anterior circulation stroke on acute neurological deterioration, the 3-month functional outcome and the occurrence of symptomatic ICH. METHODS We analyzed data from a single stroke unit registry of 384 consecutive patients with anterior circulation infarction, treated with intravenous tPA. Logistic regression models were used to assess if HMCAS was independently associated with predefined outcome definitions. RESULTS We found a HMCAS in 104 patients (27%). The HMCAS was related to the risk of early neurological deterioration (p=0.04) and poor functional outcome (p<0.001) on univariate analysis. The incidence of symptomatic ICH was not significantly different between patients with and without HMCAS (7% versus 6%, p=0.81). In the multivariable analysis, the presence of HMCAS was significantly associated with a poor outcome (p=0.004). CONCLUSIONS The HMCAS is associated with early neurological deterioration and poor functional outcome, but not with symptomatic ICH.

Thromboelastography in patients with cerebral venous thrombosis

INTRODUCTION Cerebral venous thrombosis (CVT) is a rare presentation of venous thrombosis and has been associated with many conditions. In about 20% no risk factor is identified. The aim of this study was to assess the clot formation by thromboelastography (TEG) in patients with a history of CVT compared with healthy controls. MATERIALS AND METHODS TEG analysis was performed on recalcified blood samples of 19 CVT patients from a single centre cohort and 1:1 sex/ age (+/-3 year) matched controls. Four TEG parameters were monitored: reaction time (r) to clot initiation, time to reach a 20 mm level of clot formation (K), slope angle alpha from r to K (alpha) and maximum vertical amplitude (MA). Patients were tested for thrombophilic defects, including deficiencies of antithrombin, protein C and protein S, factor V Leiden, prothrombin G20210A mutation, lupus anticoagulant, antiphospholipid antibodies, and high factor VIII levels. RESULTS Thrombophilia testing identified a prothrombotic abnormality in 11 patients (58%). Sixteen patients (84%) had one or more transient risk factor. There were no significant differences in TEG parameters between CVT patients and controls, neither between the subgroup of patients with a thrombophilic defect and controls. Seven of all patients (37%), including 5 patients with abnormal thrombophilia testing, and 5 controls (26%) had one or more TEG hypercoagulable parameters. CONCLUSIONS A persistent hypercoagulable state which could have predisposed to venous thrombosis in CVT patients and in the subgroup of patients with a thrombophilic defect could not be demonstrated by TEG.

Long-Term Sequelae after Cerebral Venous Thrombosis in Functionally Independent Patients

BACKGROUND The majority of survivors of cerebral venous thrombosis (CVT) regain functional independence, but it is unclear whether these patients experience long-term sequelae. The aim of this case-control study was to assess: (1) frequency of headache, fatigue, depression, and concentration impairment; and (2) impact of these sequelae on daily life and employment in patients with CVT who are functionally independent. METHODS We included 44 patients with CVT older than 15 years diagnosed between January 1997 and July 2006 who were functionally independent (modified Rankin scale score <or= 2) at least 12 months after CVT. Healthy control subjects were matched for age and sex. Headache was assessed by the Headache Impact Test, fatigue with the Fatigue Severity Scale, depression by the Center for Epidemiological Studies Depression Scale, and concentration impairment with the cognition dimension of the 6-dimensional EuroQol. We studied the psychosocial impact (based on the Severity Impact Profile 68) and the impact on employment status. RESULTS Median follow-up was 63 months (range 12-124). In all, 33 patients (75%) reported concentration impairment, 19 (43%) had headache, 13 (30%) were depressive, and 13 (30%) experienced fatigue. All sequelae were more reported by patients than control subjects. The sequelae were correlated with each other, and with a higher psychosocial impact. Working was impossible for 8 (21%) and difficult for 13 (34%) of previously employed patients. CONCLUSION In this case-control study, patients with CVT classified as having a good (independent) outcome often experience long-term symptoms that have a negative impact on their psychosocial and employment status.

Development and validation of a predictive outcome score of cerebral venous thrombosis

BACKGROUND AND PURPOSE Cerebral venous thrombosis (CVT) is a rare disease with a variable outcome. The aim of this study was to develop and validate a predictive outcome score for CVT patients. METHODS The score was based on the 8 predictive variables of poor outcome (modified Rankin Scale score>2) from the International Study on Cerebral Vein and Dural Sinus Thrombosis: age >37, male, mental status disorder, coma, intracranial hemorrhage, deep CVT, CNS infection, and malignancy. To assign a weighted index (WI), the natural logarithm of the hazard ratio of each variable was calculated, multiplied by 10 and rounded to the nearest integer. The individual score of each patient was the sum of the WI. The validation sample consisted of a retrospective single center cohort of 90 CVT patients. RESULTS Sixteen patients (18%) had a poor outcome. The predictive score had an area under the receiver operating characteristic curve of 0.81 (95% CI 0.71-0.90). The cut-off score with the maximum sum of sensitivity and specificity was a score> or =14 with sensitivity of 88% (81%-95%) and specificity of 70% (61%-79%). The predictive value of a score<14 for good outcome was 96% (92%-100%), whereas the predictive value of a score> or =14 for poor outcome was 39% (29%-49%). CONCLUSIONS This relatively simple predictive outcome score may be useful in CVT patients. A cut-off score of 14 reliably predicts good outcome, but is less accurate in predicting poor outcome.