Ana Catarina Fonseca

Drug Abuse and Stroke

Cerebrovascular disorders contribute to the morbidity and disability associated with illicit drug use. Drug abusers have an increased risk of both hemorrhagic and ischemic stroke. In geographic areas with a high prevalence of illicit drug use, drug abuse is a frequent cause of stroke in the young adult. The illicit drugs more commonly associated with stroke are psychomotor stimulants, such as amphetamine and cocaine. Less commonly implicated are opioids and psychotomimetic drugs, including cannabis. Toxicology screening for illicit drugs should be done in young patients with stroke with no obvious cause, or if suggested by history or examination. Although in some patients the mechanism of stroke is identified using neuroimaging and other modern diagnostic tools, in a sizeable fraction of cases the mechanism of stroke remains unclear. Further studies are needed to elucidate the role of hemodynamic and immunologic mechanisms in these cases.

N-terminal probrain natriuretic peptide as a biomarker of cardioembolic stroke

Background and purpose N-terminal probrain natriuretic peptide, which is mainly produced by the heart, is increased in acute stroke. We aimed to determine if N-terminal probrain natriuretic peptide could be a biomarker for ischemic stroke with a cardioembolic cause. Methods Consecutive sample of acute stroke patients admitted to a Stroke Unit. Ischemic stroke subtype was classified using the TOAST classification. Blood samples were drawn within 72 h after stroke onset. Serum N-terminal probrain natriuretic peptide concentration was measured using an electrochemiluminescence immunoassay. Mean values of N-terminal probrain natriuretic peptide were compared between patients with hemorrhagic stroke vs. ischemic stroke, cardioembolic stroke vs. noncardioembolic stroke, cardioembolic stroke with atrial fibrillation vs. noncardioembolic stroke using t-test. Receiver operating characteristic curves were used to test the ability of N-terminal probrain natriuretic peptide values to identify cardioembolic stroke and cardioembolic stroke with atrial fibrillation. Results Ninety-two patients were included (66 with ischemic stroke) with a mean age of 58·6 years. Twenty-eight (42·4%) ischemic strokes had a cardioembolic cause. Mean N-terminal probrain natriuretic peptide values for cardioembolic stroke were significantly higher (P < 0·001) (491·6; 95% confidence interval 283·7–852·0 pg/ml) than for noncardioembolic ischemic stroke (124·7; 86·3–180·2 pg/ml). The area under the receiver operating characteristic curve for N-terminal probrain natriuretic peptide in cardioembolic stroke was 0·77. The cut-off point with the highest sensitivity and specificity was set at 265·5 pg/ml (71·4% and 73·7% respectively). The area under the curve of N-terminal probrain natriuretic peptide for cardioembolic stroke related to atrial fibrillation was 0·92, cut-off was set at 265·5 pg/ml (sensitivity 94·4%, specificity 72·9%). Conclusion N-terminal probrain natriuretic peptide is a biomarker with a good accuracy to predict ischemic stroke of cardioembolic cause, namely associated with atrial fibrillation.

N-terminal pro-brain natriuretic peptide shows diagnostic accuracy for detecting atrial fibrillation in cryptogenic stroke patients.

Background Diagnosing paroxysmal atrial fibrillation in patients with stroke can be difficult. We aimed to determine if N-terminal pro-brain natriuretic peptide can help identify paroxysmal atrial fibrillation in cryptogenic stroke. Methods and results Among 264 ischemic stroke patients, serum levels of N-terminal pro-brain natriuretic peptide were measured within 72 h of stroke onset. In cryptogenic stroke patients, 24-h Holter monitoring was used to look for paroxysmal atrial fibrillation within the first week and also three-and six-months after admission. First, patients with a defined etiology were used to construct a receiver operating characteristic curve for the diagnosis of atrial fibrillation. From this curve, the sensitivity and specificity of preestablished cutoff points for the diagnosis of atrial fibrillation were calculated. A logistic regression was performed to assess the independent relationship of the logarithm of N-terminal pro-brain natriuretic peptide levels with atrial fibrillation. The cutoff points were then evaluated in patients with cryptogenic stroke. Results One hundred eighty-four patients had a specific stroke etiology. Fifty-five patients had atrial fibrillation. Using multivariate analysis, the logarithm of N-terminal pro-brain natriuretic peptide levels was independently associated with atrial fibrillation. The area under the receiver operating characteristic curve of N-terminal pro-brain natriuretic peptide for the diagnosis of atrial fibrillation was 0·91 (95% confidence interval 0·87–0·95). The cutoff point of 265·5 pg/ml had a sensitivity of 100% and specificity of 70·5% for the diagnosis of atrial fibrillation. The cutoff point of 912 pg/ml had a sensitivity of 81·8% and a specificity of 87·5%. Eighty patients had a cryptogenic stroke. In 17, paroxysmal atrial fibrillation was found during follow-up. In these patients, the area under the curve for the diagnosis of paroxysmal atrial fibrillation was 0·83. The cutoff point of 265·5 had a sensitivity of 88·2% and a specificity of 61·9%. The cutoff point of 912 pg/ml had a sensitivity of 47·1% and a specificity of 88·9%. Conclusion N-terminal pro-brain natriuretic peptide has good accuracy in predicting the presence of paroxysmal atrial fibrillation in patients with cryptogenic stroke and can help to identify these patients.

Chapter 7 – Infective endocarditis

Infective endocarditis is a serious disease of the endocardium of the heart and cardiac valves, caused by a variety of infectious agents, ranging from streptococci to rickettsia. The proportion of cases associated with rheumatic valvulopathy and dental surgery has decreased in recent years, while endocarditis associated with intravenous drug abuse, prosthetic valves, degenerative valve disease, implanted cardiac devices, and iatrogenic or nosocomial infections has emerged. Endocarditis causes constitutional, cardiac and multiorgan symptoms and signs. The central nervous system can be affected in the form of meningitis, cerebritis, encephalopathy, seizures, brain abscess, ischemic embolic stroke, mycotic aneurysm, and subarachnoid or intracerebral hemorrhage. Stroke in endocarditis is an ominous prognostic sign. Treatment of endocarditis includes prolonged appropriate antimicrobial therapy and in selected cases, cardiac surgery. In ischemic stroke associated with infective endocarditis there is no indication to start antithrombotic drugs. In previously anticoagulated patients with an ischemic stroke, oral anticoagulants should be replaced by unfractionated heparin, while in intracranial hemorrhage, all anticoagulation should be interrupted. The majority of unruptured mycotic aneurysms can be treated by antibiotics, but for ruptured aneurysms, endovascular or neurosurgical therapy is indicated.

Reversible bilateral sensorineural hearing loss in a woman with cerebral venous thrombosis

JO N 2963 Brain MRI disclosed extensive CVT involving the superior longitudinal sinus, the straight sinus and proximal portion of both transverse sinuses. There were no visible changes in the inner ear. Laboratory examinations showed homozygosity for MTHFR A1298C, increased serum homocysteine, reduced vitamin B12 and folic acid. The patient was treated since admission with repeated therapeutic LP, furosemide and acetazolamide to control increased intracranial pressure and with low molecular weight heparin, vitamin B12 and folic acid for the CVT. Three days after admission, evaluation of hearing loss showed moderate (56–70 dB) bilateral sensorineural hearing loss, mainly affecting low frequencies (Fig. 1) with normal tympanogram and otoscopy. Both acoustic reflexes were absent ipsilaterally and contralaterally. LP performed on the same day showed an opening pressure of 43 cmH2O. Three weeks later, LP opening pressure was 26 cmH2O, hearing had improved 10–20 dB (right-left, respectively) and there was no ophthalmoparesis. Cerebral angiography showed recanalization of the dural sinuses. However, intracranial hypertension did not regress on subsequent LP and a lumboperitoneal shunt was placed three months after the first observation. One month after shunting, the audiogram (Fig. 2) of the left ear had normalized and that of the right ear showed a mild low frequency hearing loss (45–40 dB improvement, right and left). Acoustic reflexes were still absent. Visual loss persisted and papilledema had been replaced by optical nerve atrophy. CVT may have contributed to sensorineural hearing loss by inducing increased intracranial pressure. This can be explained by two mechanisms: 1. Increased pressure in the subAna C. Fonseca Luísa Albuquerque José M. Ferro

Epileptic manifestations in stroke patients treated with intravenous alteplase

Intravenous alteplase (rtPA) may be associated with seizures and epileptic activity in the electroencephalogram (EEG). The aim of this work was to compare the frequency of seizures and EEG abnormalities between stroke patients treated and not treated with rtPA.

Improvement of sleep architecture in the follow up of a patient with bilateral paramedian thalamic stroke

Normal sleep architecture and arousal require an intact thalamus. Thalamic vascular lesions, particularly in the paramedian region may cause arousal disturbances and hypersomnolence. Although hypersomnolence is one of the main characteristics of acute bilateral paramedian thalamic infarcts, there are only scarce reports in literature concerning polysomnographic follow-up of these patients. The few reported cases in literature show that sleep stages do not significantly change from the acute to chronic phase. We present a case report of a patient with a bilateral paramedian thalamic infarct in which a polysomnographic evaluation of sleep was performed four days and five months after stroke. In the acute phase, polysomnography showed an impairment of phase 2 NREM and absence of phase 3 and 4 NREM with absent sleep spindles. After the acute stroke phase, hypersomnolence improved and sleep spindles reappeared as well as phase 3 and 4 of NREM sleep. Our patient clear clinical and polysomnographic improvement makes us suppose that in this case the initial impairment could have been essentially due to a functional transitory impairment of the thalamocortical and corticothalamic connections. This case report is peculiar because it discloses a marked improvement of sleep architecture which to the best of our knowledge has not been clearly described before.

Sneeze as a precipitating factor of cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease (<1% of all strokes) [1]. Several conditions have been pointed as causative factors and include, amongst others, genetic and acquired prothrombotic conditions, infections, inflammatory diseases, haematological disorders and trauma [2]. When trauma is mentioned as a cause of CVT, it mainly refers to major head or neck trauma, including penetrating injury of skull fractures, injury to sinuses or jugular veins or neurosurgical procedures [2]. There are a few published reports associating trivial trauma, such as sneezing, jumping from a small height and a golf swing with CVT [3,4,5]. We report a patient who presented with an extensive sinus venous cerebral thrombosis after a violent sneeze. The association between both phenomena and its hypothesized pathogenesis are discussed.

Neck hematoma after intravenous thrombolysis for stroke treatment.

or sign of trauma. Neurological examination disclosed hemi-inattention, left gaze palsy, left homonymous hemianopia, dysarthria, left facial paresis, hemisensory loss and hemiparesis (NIHSS score 14). A brain computerized tomography (CT) scan was unremarkable. Platelet count, activated partial thromboplastin time and prothrombin time were normal. Intravenous rtPA administration was started 2.5 h after symptom onset with a total alteplase dose of 68 mg (0.9 mg/kg). Fifty minutes after perfusion start, hemi-inattention and limb weakness increased (NIHSS score 17). At the end of rtPA perfusion, a right cervical hematoma was noticed ( fig. 1 a). Cervical CT performed 1 h afterwards showed a hematoma surrounding the right internal carotid artery (ICA) extending to the subcutaneous neck tissue and a diminished caliber of the right ICA lumen ( fig. 1 b, c). There was no further deterioration of the neurological status or vital parameters, although an increase in the superficial neck hematoma was noticed. No specific treatment for the cervical hematoma was provided. The next day, brain CT confirmed a large infarction in the territory of the right middle cerebral artery. Cervical ultrasonography and digital brain angiography showed a non-atherosclerotic occlusion of the right ICA. Magnetic resonance imaging of the neck with fat-suppressed T 1 -weighted sequences performed 2 weeks after stroke onset disclosed a hematoma surrounding the initial segment of the right ICA. Coagulation, autoimmunity and serological studies were unremarkable. A transesophageal echocardiogram revealed a ‘patent foramen ovale’. The patient was discharged receiving aspirin 250 mg/day. Introduction Bleeding is a feared adverse effect of intravenous thrombolysis. Despite the widespread use of intravenous recombinant tissuetype plasminogen activator (rtPA) in stroke, there are few significant extracranial bleedings [1–3] . We report a case of neck hematoma after intravenous rtPA for stroke, which to our best knowledge has not been previously described.

Seizures, electroencephalographic abnormalities, and outcome of ischemic stroke patients

Seizures and electroencephalographic (EEG) abnormalities have been associated with unfavorable stroke functional outcome. However, this association may depend on clinical and imaging stroke severity. We set out to analyze whether epileptic seizures and early EEG abnormalities are predictors of stroke outcome after adjustment for age and clinical/imaging infarct severity.