J. Masjuan

Paraneoplastic anti-N-methyl -D -aspartate receptor encephalitis associated with ovarian teratoma

To report the autoantigens of a new category of treatment‐responsive paraneoplastic encephalitis.

Recurrent Stroke and Massive Right-to-Left Shunt Results From the Prospective Spanish Multicenter (CODICIA) Study

Background and Purpose— Few studies have prospectively examined the risk of recurrent stroke associated with patent foramen ovale. We present the results of the Spanish right-to-left shunt (RLSh) multicenter study. Methods— Four hundred eighty-six patients with cryptogenic stoke were included at 17 participating hospitals. Patients were examined by contrast transcranial Doppler methods at baseline. The magnitude of RLSh was quantified during the Valsalva maneuver. Transthoracic and/or transesophageal echocardiography, computed tomography scan, or magnetic resonance imaging was performed. Functional outcome and stroke recurrence were evaluated at 3 months and yearly thereafter. The independent relation between RLSh magnitude and stroke recurrence was analyzed by logistic-regression analysis in the whole group and in the younger subgroup (<55 years). Results— Massive RLSh was detected in 200 patients (41.2%). The mean follow-up was 729±411 days. Stroke recurrence was low (5.8%, n=28) and similar in patients with massive RLSh, with nonmassive RLSh, and with no RLSh, in both the younger group (3.4% vs 2.3% vs 4.5%, respectively; P=0.75) and in the whole population (5.0% vs 6.2% vs 6.3%, respectively; P=0.58). Regression analysis found no association between massive RLSh and recurrent stroke in either group (in the whole population, odds ratio=0.94; 95% CI, 0.36 to 2.40; P=0.89; in the younger population, odds ratio=0.93; 95% CI, 0.18 to 4.91; P=0.93). These results were similar when concurrent atrial septal aneurysm and massive RLSh were analyzed and when antithrombotic treatment and concomitant stroke risk factors were included. Conclusions— These results suggest that neither massive RLSh nor massive RLSh with concurrent atrial septal aneurysm is an independent risk factor for recurrent stroke, in either the general or younger stroke populations.

Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial)

BACKGROUND Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial. METHODS We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890. RESULTS 2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364). No significant differences were reported in the safety variables nor in the rate of adverse events. INTERPRETATION Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke. FUNDING Ferrer Grupo.

Decompressive Surgery in Cerebrovenous Thrombosis A Multicenter Registry and a Systematic Review of Individual Patient Data

Background and Purpose— Herniation attributable to unilateral mass effect is the major cause of death in cerebral venous thrombosis (CVT). Decompressive surgery may be lifesaving in these patients. Methods— Retrospective registry of cases of acute CVT treated with decompressive surgery (craniectomy or hematoma evacuation) in 22 centers and systematic review of all published cases of CVT treated with decompressive surgery. The primary outcome was the score on the modified Rankin Scale (mRS) score at last follow-up, dichotomized between favorable (mRS score, 0–4) and unfavorable outcome (mRS score, 5 or death). Secondary outcomes were complete recovery (mRS score 0–1), independence (mRS score, 0–2), severe dependence (mRS score, 4–5), and death at last available follow-up. Results— Sixty-nine patients were included and 38 were from the registry. Decompressive craniectomy was performed in 45 patients, hematoma evacuation was performed in 7, and both interventions were performed in 17 patients. At last follow-up (median, 12 months) only 12 (17.4%) had un unfavorable outcome. Twenty-six (37.7%) had mRS score 0 to 1, 39 (56.5%) had mRS score 0 to 2, 4 (5.8%) were alive with mRS score 4 to 5, and 11 (15.9%) patients died. Three of the 9 patients with bilateral fixed pupils recovered completely. Comatose patients were less likely to be independent (mRS score 0–2) than noncomatose patients (45% versus 84%; P=0.003). Patients with bilateral lesions were more likely to have unfavorable outcomes (50% versus 11%; P=0.004) and to die (42% versus 11%; P=0.025). Conclusions— In CVT patients with large parenchymal lesions causing herniation, decompressive surgery was lifesaving and often resulted in good functional outcome, even in patients with severe clinical conditions.

Thrombolysis treatment for acute ischaemic stroke in a patient on treatment with dabigatran

Thrombolysis treatment for acute ischaemic stroke in a patient on treatment with dabigatran -

Off-label intravenous thrombolysis in acute stroke.

Background and purpose: Therapy for stroke with intravenous tissue plasminogen activator (IV‐tPA) is hampered by tight licensing restrictions; some of them have been discussed in recent literature. We assessed the safety and effectiveness of off‐label IV‐tPA in the clinical settings.

TREATMENT-RESPONSIVE SUBACUTE LIMBIC ENCEPHALITIS AND NMDA RECEPTOR ANTIBODIES IN A MAN

Disturbances of memory, behavior, cognition, and seizures can result from immune-mediated encephalitides. These disorders can be paraneoplastic or not and may associate with several antibodies.1 Recently, a treatment-responsive paraneoplastic encephalitis that associates with antibodies to NR1/NR2 heteromers of the NMDA receptor (NMDAR) was reported.2 Patients were young women with teratomas, usually of the ovary, who presented with prominent psychiatric symptoms, and less frequently with features of limbic encephalitis. We report a man with treatment-responsive limbic encephalitis and antibodies to NR1/NR2 heteromers. ### Case report. For 3 months this 53-year-old man had progressive short-term memory deficits and disorientation that forced him to leave his job. During the month before hospital admission he had multiple episodes compatible with partial complex seizures. He had no past medical history of interest. The neurologic examination only revealed short-term memory deficits and impairment of temporal orientation. Blood cell count, general chemistry, B12, folic acid, thyroid function test, thyroglobulin antibodies, RPR, Lyme serology, antibodies to double stranded DNA, and SSA/Ro and SSB/La were unrevealing. CSF analysis showed 5 WBC/μL (100% lymphocytes) and normal glucose and protein concentration. Serum and CSF disclosed the same oligoclonal IgG bands. Paraneoplastic antineuronal and VGKC antibodies were negative. EEG demonstrated bilateral temporal lobe epileptic activity. MRI of the brain revealed noncontrast enhancing T2 and FLAIR hyperintensities involving the medial aspect of the temporal lobes and nonspecific hyperintensities in the frontal lobes (figure, A). Ultrasound of the testis, CT of the chest, abdomen and …

Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores.

Background: Several clinical scales have been developed for predicting stroke recurrence. These clinical scores could be extremely useful to guide triage decisions. Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients. Methods: Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). A neurologist treated all patients within the first 48 h after symptom onset. The duration and typology of clinical symptoms, vascular risk factors and etiological work-ups were prospectively recorded in a case report form in order to calculate established prognostic scores. We determined the early short-term risk of stroke (at 7 and 90 days). To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. Cox proportional hazards multivariate analyses determining independent predictors of stroke recurrence using the different components of all clinical scores were calculated. Results: We calculated clinical scales for 1,137 patients (90.6%). Seven-day and 90-day stroke risks were 2.6 and 3.8%, respectively. Large-artery atherosclerosis (LAA) was observed in 190 patients (16.7%). We could confirm the predictive value of the ABCD3 score for stroke recurrence at the 7-day follow-up [0.66, 95% confidence interval (CI) 0.54–0.77] and 90-day follow-up (0.61, 95% CI 0.52–0.70), which improved when we added vascular imaging information and derived ABCD3V scores by assigning 2 points for at least 50% symptomatic stenosis on carotid or intracranial imaging (0.69, 95% CI 0.57–0.81, and 0.63, 95% CI 0.51–0.69, respectively). When we evaluated each component of all clinical scores using Cox regression analyses, we observed that prior TIA and LAA were independent predictors of stroke recurrence at the 7-day follow-up [hazard ratio (HR) 3.97, 95% CI 1.91–8.26, p < 0.001, and HR 3.11, 95% CI 1.47–6.58, p = 0.003, respectively] and 90-day follow-up (HR 2.35, 95% CI 1.28–4.31, p = 0.006, and HR 2.20, 95% CI 1.15–4.21, p = 0.018, respectively). Conclusion: All published scores that do not take into account vascular imaging or prior TIA when identifying stroke risk after TIA failed to predict risk when applied by neurologists. Clinical scores were not able to replace extensive emergent diagnostic evaluations such as vascular imaging, and they should take into account unstable patients with recent prior transient episodes.

Stroke mimics treated with thrombolysis: further evidence on safety and distinctive clinical features.

Background: Patients who present with symptoms mimicking ischaemic stroke (IS), but have a different diagnosis, are known as stroke mimics (SM). The necessity for rapid administration of intravenous thrombolysis in patients with acute IS may lead to treatment of patients with conditions mimicking stroke. A variable proportion of patients with SM (1.4–14%) are currently treated with intravenous tissue plasminogen activator therapy (IV-tPA). The outcome of these patients is generally favourable and complications are rather infrequent. We aimed to determine the frequency, clinical features and prognosis of SM patients treated with IV-tPA in an experienced stroke centre. Methods: A prospective registry was assembled with patients treated with IV-tPA at our stroke unit from January 2004 to December 2011. We recorded age, gender, baseline National Institutes of Health Stroke Scale (NIHSS) score, treatment delay, vascular risk factors, clinical syndrome and aetiology. We retrospectively analysed the clinical characteristics of SM, safety (symptomatic intracranial haemorrhage and mortality) and outcome measures (modified Rankin Scale at 3 months, mRS) and compared them with IS patients. Results: 621 patients were treated with IV-tPA during the study period, 606 (97.5%) were IS and 15 (2.4%) were SM. The aetiology of SM was somatoform disorders (5), headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome (3), herpetic encephalitis (2), glial tumours (2), and migraine with aura, focal seizure and cortical vein thrombosis in single cases. SM were younger (72 ± 14 vs. 53.7 ± 16 years, p < 0.05), had a lower baseline deficit [NIHSS 13 (9–18) vs. 8 (5–10), p < 0.05], fewer vascular risk factors, and left hemisphere symptoms were predominant (80 vs. 52.4%, p < 0.05). Global aphasia without hemiparesis (GAWH) was the presenting symptom in 8 (54%) SM and 44 (7%) IS (p < 0.05). Multimodal computed tomography was performed in 3 SM patients and showed perfusion deficits in 2 of them. No intracranial haemorrhage or disability (functional outcome at 3 months, mRS >2) was recorded in any SM patient. Conclusions: The use of intravenous thrombolysis appears to be safe in our SM patients, and prognosis is universally favourable. Somatoform disorder and HaNDL syndrome were prominent causes, and GAWH the most common presentation. The safety of thrombolysis in SM suggests that delaying or withholding treatment may be inappropriate: the benefit of thrombolysis in case of IS may outweigh the risks of treating an SM. Further studies may assess the future role of multimodal computed tomography in the differential diagnosis between IS and SM.

Guías de actuación clínica en la hemorragia intracerebral

Intracerebral haemorrhage accounts for 10%-15% of all strokes; however it has a poor prognosis with higher rates of morbidity and mortality. Neurological deterioration is often observed during the first hours after onset and determines poor prognosis. Intracerebral haemorrhage, therefore, is a neurological emergency which must be diagnosed and treated properly as soon as possible. In this guide we review the diagnostic procedures and factors that influence the prognosis of patients with intracerebral haemorrhage and we establish recommendations for the therapeutic strategy, systematic diagnosis, acute treatment and secondary prevention for this condition.