It is a cross-sectional study conducted during the period from July 2016 till August 2018. The sample consisted of 482 ischemic stroke patients admitted to the stroke unit during the period from July 2016 to August 2018 of which 55 patients were classified to be of undetermined etiology according to (TOAST) classification [6]. NIIHSS and MRS were done for all patients on admission and after 1 month.
Inclusion criteria and patient selection
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Age: more than 18 years. Clinical presentation of cerebrovascular stroke (defined as the presence of rapidly developing focal neurological signs or symptoms of vascular origin that persists for more than 1 h) [7]. Routine diagnostic tools [routine lab, carotid ultrasound, trans-thoracic echocardiography (TTE), electrocardiogram (ECG)] were normal to categorize patient as cryptogenic stroke as minimum required diagnostic tools mentioned in American Heart and Stroke Associations [8].
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Cryptogenic stroke patients were excluded from enrollment if one of the following criteria was met:
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Age less than 18 years or more than 60 years
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Medically unstable patients or have contraindications to used investigations
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Patients who rejected enrollment in the study
Methods
Written informed consent was obtained from the patients participating in the study, or their first-degree relatives if the patient was unable to provide consent due to weakness or disturbed conscious level, after informing them about the study rationale and their right to withdraw from the study at any time without any consequences. All patients were subjected to history taking including personal data, past history, history of vascular risk factors, detailed history of current illness.
General and neurological examination
Laboratory investigations
ESR, CRP, ANA, Anti DNA, anticardiolipin antibody, lupus anticoagulant, ANCA P and ANCA C, Protein C, protein S, and antithrombin ш were done for all patients to exclude autoimmune etiologies and hypercoagulopathies. CT brain to exclude intracerebral hemorrhage. MRI brain (Philips 1.5 Tesla) (diffusion weighted, Flair, T1, T2, and T2* images) and MRA. Transesophageal echocardiography (GE Healthcare, vivid E9 with 6 DT-D TEE probe) was done for detection of PFO and RLS. Agitated saline was injected and monitored to detect right to left shunting (without and then with Valsalva maneuver). TEE was also used to detect other findings: atrial septal aneurysm (ASA), intracardiac thrombi, and aortic atheromatous plaques. Forty-eight hours Holter ECG (Norav Holter NH-301). Contrast-enhanced transcranial color-coded duplex (esaote mylab 5, Italy using 2-4 MHZ phased array probe) was done for patients for detection of microembolic signals in the middle cerebral artery for confirmation of the presence of patent foramen ovale and presence of right to left shunting by using agitated saline consisted of 1 ml of air vigorously mixed with 8.5 ml of saline solution and injected into the antecubital vein via a three-way stopcock immediately after contrast preparation. If no microbubbles were detected after the first injection, then a further two injections were made with a Valsalva maneuver. Microembolic signals were considered positive if detected within 30 s from contrast injection and grading was considered grade 1 (microemboli 1-10), grade (microemboli 11-30), and grade 3 (microemboli 31-100) [9].
Statistical analysis
Statistical analysis was conducted using SPSS V24 (SPSS, IBM, Chicago, IL, USA). P values were considered significant if < 0.05. Descriptive statistics were used for patient demographics, chi-squared test was used to compare normally distributed demographics, likelihood ratio was used to compare abnormally distributed variables. T test was used to compare means of NIH and mRs on admission and at 3 months, as well as age distribution. Kaplan-Meier survival curves were plotted to display the relation of time to Holter, and arrhythmia discovery.
