Patent foramen ovale and cryptogenic stroke: the hole story.

Despite 3 recent randomized clinical trials, the management of patients with cryptogenic stroke and patent foramen ovale remains unsettled. The primary results of Evaluation of the STARFlex Septal Closure System in Patients with a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE), Percutaneous Closure of Patent Foramen Ovale in Cryptogenic Stroke (PC), and Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) were the same; the intent to treat analysis for the primary end point in all 3 trials failed to demonstrate superiority of device closure compared with medical therapy. CLOSURE put the brakes on indiscriminate device closure of patent foramen ovales in patients with cryptogenic stroke or transient ischemic attack. RESPECT suggested, but did not prove, that highly selected patients without vascular risk factors, with a cortical infarct on baseline magnetic resonance imaging and a substantial patent foramen ovale shunt may benefit from the Amplatzer device during a multiple-year period. In the absence of definitive clinical trial results, the precise definition of which patient subgroups should be considered for patent foramen ovale device closure should be agreed to by the stakeholder societies and the Food and Drug Administration.

Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study.

BACKGROUND AND PURPOSE: Adequate diagnosis of atrial fibrillation (AF), including paroxysmal AF, is an important part of stroke workup. Prolonged ECG monitoring may improve the detection of paroxysmal, previously undiagnosed AF (unknown AF). Therefore, we evaluated systematic 72-hour Holter ECG monitoring to detect unknown AF for the workup of patients with stroke. METHODS: Unselected survivors of a stroke or transient ischemic attack (TIA) without known AF were enrolled in a prospective, multicenter cohort study of 72-hour Holter ECG monitoring in 9 German secondary and tertiary stroke centers between May 2010 and January 2011. In addition to standardized workup of stroke pathogenesis according to the German Stroke Unit protocol, all patients underwent 72-hour Holter ECG monitoring directly after admission. All ECGs were centrally analyzed by 2 independent observers. We determined the proportion of unknown AF and compared the detection rates of 72- and 24-hour monitoring. RESULTS: A total of 1135 patients were enrolled (mean age, 67 years [SD, 13.1 years], 45% women, 29% TIA). Unknown AF was detected in 49 out of 1135 patients (4.3%, [95% confidence interval, 3.4-5.2%]) by 72-hour ECG monitoring. Unknown AF was diagnosed in 29 patients (2.6%) within the first 24 hours of ECG monitoring, and in 20 more patients only by 72 hours of ECG monitoring. The number needed to screen by 72-hour ECG was 55 patients (95% confidence interval [35-123]) for each additional AF diagnosis. Patients with unknown AF were significantly older and had more often a history of previous stroke. Patients with unknown AF were equally distributed within categories of pathogenesis according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. CONCLUSIONS: In unselected survivors of stroke or TIA, 72-hour ECG monitoring is feasible and improves the detection rate of silent paroxysmal AF.

Peginterferon beta-1a was associated with high adherence and satisfaction in patients with multiple sclerosis in a German real-world study.

BACKGROUND: Peginterferon beta-1a was developed for treatment of relapsing-remitting multiple sclerosis (RRMS) to provide an interferon with increased exposure to facilitate adherence by reducing frequency of application. This non-interventional observational study investigated the adherence to peginterferon beta-1a in real-world clinical practice settings. METHODS: This prospective study was conducted from 1/2015 to 1/2018 at 77 German MS sites. Adult patients with RRMS (previously treated or treatment-naïve) receiving peginterferon beta-1a (125 µg SC every 2 weeks) were eligible for participation. Data were documented every 3 months over 2 years (nine visits). The primary endpoint was the percentage of patients with overall adherence defined as ⩽10% of injections not administered throughout the 24-month observation period. Secondary endpoints included persistence, patient satisfaction, efficacy (relapse activity, disability progression), and tolerability. Patients were invited to participate in an individualised patient support programme. RESULTS: Out of 250 enrolled patients, 190 (aged 18-74 years, 75.3% female) were included in the efficacy analysis. Of those, 74 patients completed the study; 33.2% were treatment-naïve. The proportion of patients with an overall adherence of >90% was 75.7% (95% CI 67.9-81.6). The annualised relapse rate was 0.17. Compared with previous therapies, the scores for treatment satisfaction and convenience were markedly higher with peginterferon beta-1a. Overall, 87.4% participated in the patient support programme, and 47.8% of patients reported adverse events. CONCLUSIONS: Adherence to the bi-weekly treatment with peginterferon beta-1a was very high. Although adherence could have been positively influenced by the well-accepted patient support programme, the extent could not be unequivocally evaluated. Clinical disease activity remained low. Peginterferon beta-1a was well tolerated, and there were no new relevant safety findings.

Decrease in shunt volume in patients with cryptogenic stroke and patent foramen ovale.

BACKGROUND: In patients with patent foramen ovale (PFO) there is evidence supporting the hypothesis of a change in right-to-left shunt (RLS) over time. Proven, this could have implications for the care of patients with PFO and a history of stroke. The following study addressed this hypothesis in a cohort of patients with stroke and PFO. METHODS: The RLS volume assessed during hospitalisation for stroke (index event/T0) was compared with the RLS volume on follow-up (T1) (median time between T0 and T1 was 10 months). In 102 patients with a history of stroke and PFO the RLS volume was re-assessed on follow-up using contrast-enhanced transcranial Doppler/duplex (ce-TCD) ultrasound. A change in RLS volume was defined as a difference of ≥20 microembolic signals (MES) or no evidence of RLS during ce-TCD ultrasound on follow-up. RESULTS: There was evidence of a marked reduction in RLS volume in 31/102 patients; in 14/31 patients a PFO was no longer detectable. An index event classified as cryptogenic stroke (P < 0.001; OD = 39.2, 95% confidence interval 6.0 to 258.2) and the time interval to the follow-up visit (P = 0.03) were independently associated with a change in RLS volume over time. CONCLUSIONS: RLS volume across a PFO decreases over time, especially in patients with cryptogenic stroke. These may determine the development of new strategies for the management in the secondary stroke prevention.

Torticollis under cyclobenzaprine.

The muscle-relaxing 5-HT(2) receptor antagonist cyclobenzaprine is structurally closely related to amitriptyline. It is widely used to treat patients presenting with back pain and fibromyalgia. Very rarely cyclobenzaprine toxicity can result in extrapyramidal symptoms, but occurrence of torticollis has not been reported so far. We report on a patient presenting with torticollis and myoclonic movements after treatment with cyclobenzaprine, who was successfully treated with intravenous biperiden. This case might be additional evidence for the necessity of appropriate dosage in case of liver impairment. Secondly there are possibly consequences as regards the therapy of motor side effects.

Development and validation of a score to detect paroxysmal atrial fibrillation after stroke.

OBJECTIVE: Prolonged monitoring times (72 hours) are recommended to detect paroxysmal atrial fibrillation (pAF) after ischemic stroke but this is not yet clinical practice; therefore, an individual patient selection for prolonged ECG monitoring might increase the diagnostic yield of pAF in a resource-saving manner. METHODS: We used individual patient data from 3 prospective studies (ntotal = 1,556) performing prolonged Holter-ECG monitoring (at least 72 hours) and centralized data evaluation after TIA or stroke in patients with sinus rhythm. Based on the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guideline, a clinical score was developed on one cohort, internally validated by bootstrapping, and externally validated on 2 other studies. RESULTS: pAF was detected in 77 of 1,556 patients (4.9%) during 72 hours of Holter monitoring. After logistic regression analysis with variable selection, age and the qualifying stroke event (categorized as stroke severity with NIH Stroke Scale [NIHSS] score ≤5 [odds ratio 2.4 vs TIA; 95% confidence interval 0.8-6.9, p = 0.112] or stroke with NIHSS score >5 [odds ratio 7.2 vs TIA; 95% confidence interval 2.4-21.8, p < 0.001]) were found to be predictive for the detection of pAF within 72 hours of Holter monitoring and included in the final score (Age: 0.76 points/year, Stroke Severity NIHSS ≤5 = 9 points, NIHSS >5 = 21 points; to Find AF [AS5F]). The high-risk group defined by AS5F is characterized by a predicted risk between 5.2% and 40.8% for detection of pAF with a number needed to screen of 3 for the highest observed AS5F points within the study population. Regarding the low number of outcomes before generalization of AS5F, the results need replication. CONCLUSION: The AS5F score can select patients for prolonged ECG monitoring after ischemic stroke to detect pAF. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the AS5F score accurately identifies patients with ischemic stroke at a higher risk of pAF.

Embolic lesion pattern in stroke patients with patent foramen ovale compared with patients lacking an embolic source.

BACKGROUND AND PURPOSE: Multiple acute ischemic lesions on diffusion-weighted magnetic resonance imaging (DWI-MRI) are thought to be of embolic origin. However, in several patients with multiple ischemic lesions on DWI-MRI, no embolic source was detected, despite a thorough clinical work-up. Stroke etiology in such cases is then classified as cryptogenic. In other patients, a potential embolic source is limited to a patent foramen ovale (PFO) that may act as an embolic source of unsure relevance. We therefore examined the prevalence of the multiple-lesion pattern in patients with cryptogenic stroke compared with patients with PFO. METHODS: We screened 650 stroke patients by DWI-MRI. For the subsequent evaluation, we excluded patients with a cardiac embolic source other than PFO, symptomatic carotid artery disease, and other apparent stroke causes, such as dissection or vasculitis, and patients whose diagnostic work-up was incomplete. For the remaining 106 patients, we found DWI lesions in 73, who were subjected to further evaluation. RESULTS: There were no differences in the occurrence of the multiple-lesion pattern in patients with cryptogenic stroke compared with patients with PFO, either for the entire group or for the subgroup of young stroke patients who were <50 years old. Patients with PFO showed a significantly higher incidence of multiple lesions in the posterior circulation. CONCLUSIONS: The multiple-lesion pattern on DWI-MRI is not uncommon, even when extensive testing does not reveal any embolic source. Therefore, it is not possible to discriminate between cryptogenic stroke and stroke from an assumed paradoxical embolism.

[Emergency treatment of cerebral infarction by the family physician]. / Notfalltherapie des Hausarztes bei Hirninfarkt. Sind Sie für den Notruf Schlaganfall gertüstet?

The emergency treatment chain of procedures for an acute stroke begins and ends with the family physician who assumes important duties and responsibilities. The physician should be already familiar with the local treatment possibilities and suitable hospitals for cerebral infarction. High risk patients and their family members should know the symptoms of a stroke and the necessity of swift action. In an emergency, the first attending physician stabilizes the vital functions of the patient and documents the chronological appearance of the symptoms and concomitant diseases. The physician organizes the transport of the patient to an appropriate hospital, ideally one with a stroke unit, where further therapy and diagnostics are performed. Finally, the family physician controls and monitors the secondary prophylaxis.

Identification of embolic stroke patterns by diffusion-weighted MRI in clinically defined lacunar stroke syndromes.

BACKGROUND: A number of clinical syndromes describing the presentation of deep brain infarcts are called lacunar syndromes resulting from small vessel occlusion (SVO). To verify the reliability of the clinical diagnosis "lacunar syndrome," the value was investigated with diffusion-weighted MRI (DWI). METHODS AND RESULTS: A total of 73 patients (mean age 66 years; range 35 to 83 years) with sudden onset of a classical lacunar syndrome were enrolled. On the basis of the DWI findings, patients were divided into 3 groups: group 1, single subcortical lesion (<15-mm lesion; 43 patients; 59%); group 2, large (> or =15 mm) or scattered lesions in 1 vascular territory (16 patients; 22%); and group 3, multiple lesions in multiple vascular territories (14 patients; 19%). A stroke mechanism other than SVO could be identified in 17 (23%) patients. Cardiac work-up revealed a cardiac embolic source in 8 patients (11%). Duplex sonography revealed symptomatic stenosis in 9 patients (12%). Based on the work-up information, 29 patients (40%) were found to have a potential cause of stroke other than SVO. A significant correlation with >1 single lesion on DWI-MRI and a clinical proven embolic source was observed (P=0.002). In 9 patients with MRI suspicious for a pathomechanism other than SVO, no embolic source was found. CONCLUSIONS: The use of DWI-MRI improves the accuracy of the subtype diagnosis of stroke. Inaccuracy has to be expected in approximately one third if lacunar diagnosis is based on clinical and computed tomography findings. Most of these "false-positive" cases are attributable to large artery or cardiogenic embolic stroke.

Intracranial venous hemodynamics in patients with midline dislocation due to postischemic brain edema.

BACKGROUND AND PURPOSE: Cerebral venous pressure is governed by intracranial pressure, cerebral perfusion pressure, and venous outflow resistance. Therefore, changes in venous flow velocities are to be expected because of changes in intracranial pressure and brain tissue dislocation in patients with ischemic stroke and space-occupying brain edema. METHODS: In 21 prospectively recruited patients with middle cerebral artery stroke and postischemic edema, flow velocities in the basal veins, the vein of Galen, the straight sinus, and the P2 segment of the posterior cerebral artery were recorded every 0.9+/-0.5 days during the first 5 days after symptom onset with the use of transcranial color-coded duplex sonography. The midline shift of the third ventricle was determined by B-mode imaging. RESULTS: We observed an initial increase of flow velocity in the basal vein ipsilateral to the lesion, followed by a significant decrease within 5 days after symptom onset and with increasing midline shift in patients with brain herniation. In the straight sinus, flow velocity showed a biphasic U-shaped response to increasing dislocation of the third ventricle, with an initial decrease followed by an increase in the course of mass movement (midline shift 1 to 1.5 cm). A steep increase of flow velocity in the vein of Galen took place with a midline shift >1.5 cm. In the survivors these changes could not be observed. Flow velocity in the P2 segment of the posterior cerebral artery followed a typical course in neither the fatal cases nor the survivors. CONCLUSIONS: Monitoring of flow velocities in the basal cerebral veins and in the straight sinus can provide additional pathophysiological information in patients with space-occupying brain edema after acute stroke.