Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of 3 Months Daily Treatment With Selective Serotonin Reuptake Inhibitor (SSRI, Fluoxetine) on Motor Rehabilitation After Ischemic Stroke. FLAME Trial
Brief Summary: Recovery from stroke is a major process and, except for acute intravenous thrombolysis, no treatment able to enhance recovery has yet been validated. Some drugs may have a positive effect when combined with physical rehabilitation. Previous studies have shown a potential effect of catecholaminergic drugs on cerebral plasticity of stroke patients. In 2001, our group has demonstrated in a small group of stroke patients (n=8) that a single dose of fluoxetine (Selective Serotonin Reuptake Inhibitor - SSRI) improved motor performance and modulated cerebral plasticity. We conducted a phase IIb prospective, double-blind, randomized, placebo controlled study to assess the effect of a daily treatment with fluoxetin (20 mg) on motor performance in patients with mild to severe motor deficit after ischemic stroke.


Options:
A: Inclusion Criteria:

* Men and women aged from 18 to 85
* No motor relapse from a previous stroke
* Inclusion from day 5 to day 10 after stroke
* Ischemic stroke with unilateral motor deficit
* Motor NIHSS ≥ 5 on the affected side of the body
* NIHSS \< 20
* Fugl Meyer Motor Scale \<55
* Modified Rankin Scale between 1 and 5
* Informed consent obtained from the subject or a member of his family

Exclusion Criteria:

* Pregnant or breast-feeding woman
* Woman able to procreate without valid contraception
* Subject protected by law
* Concomitant disease with unfavourable prognosis within 1 year
* Drug addiction
* Allergy to fluoxetine
* Hepatic failure (TGO and TGP \>2N)
* Permanent Renal failure (Creatinin \>180micromol/l)
* Patients treated by tricyclic antidepressant, selective serotonin reuptake inhibitor, monoamine oxidase inhibitor (IMAO), and neuroleptics in the past month
* Depression requiring pharmacological treatment
* Previous stroke with motor relapse
* Fugl Meyer Motor Scale \> 55
* Modified Rankin Scale = 0 or 6
* Patients needing carotid surgery within 3 months
* Aphasia preventing correct evaluation of motor and depression scales.
B: Inclusion Criteria:

Clinical Inclusion Criteria

* Clinical diagnosis of acute ischemic stroke with unknown symptom onset (e.g., stroke symptoms recognized on awakening)
* Last known well (without neurological symptoms) \> 4.5 hours of treatment initiation
* Measurable disabling neurological deficit (defined as an impairment of one or more of the following: language, motor function, cognition, gaze, vision, neglect)
* Age 18-80 years
* Treatment can be started within 4.5 hours of symptom recognition (e.g., awakening)
* Written informed consent by patient or proxy

Imaging Inclusion Criteria:

* Acute stroke MRI including diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) completed
* MRI showing a pattern of "DWI-FLAIR-mismatch", i.e. acute ischemic lesion visibly on DWI ("positive DWI") but no marked parenchymal hyperintensity visible on FLAIR ("negative FLAIR") indicative of an acute ischemic lesion ≤4.5 hours of age

Exclusion Criteria:

Clinical Exclusion Criteria

* Planned or anticipated treatment with endovascular reperfusion strategies (e.g. intra-arterial thrombolysis, mechanical recanalization techniques)
* Pre-stroke disability (inability to carry out all daily activities, requiring some help or supervision, i.e. slight disability corresponding to an MRS score \> 1)
* Participation in any investigational study in the previous 30 days
* Severe stroke by clinical assessment (e.g. NIHSS \> 25)
* Hypersensitivity to Alteplase or any of the excipients
* Pregnancy or lactating (formal testing needed in woman of childbearing potential; childbearing potential is assumed in women up to 55 years of age)
* Significant bleeding disorder at present or within past 6 months
* Known haemorrhagic diathesis
* Manifest or recent severe or dangerous bleeding
* Known history of or suspected intracranial haemorrhage
* Suspected subarachnoid haemorrhage (even if CT is negative) or condition after subarachnoid haemorrhage from aneurysm
* History of CNS damage (e.g. neoplasm, aneurysm, intracranial or spinal surgery)
* Recent (within 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel
* Current use of anticoagulants (e.g. Phenprocoumon, Warfarin, new anticoagulants such as Dabigatran) or current use of heparin and elevated thromboplastin time (low-dose subcutaneous heparin is allowed)
* Platelet count \< 100.000/mm3 (\<100G/l)
* Blood glucose \< 50 or \> 400 mg/dl (\< 2.8 or 22.2 mmol/l)
* Severe uncontrolled hypertension, i.e. systolic blood pressure \> 185 mmHg or diastolic blood pressure \>110 mmHg or requiring aggressive medication to maintain blood pressure within these limits (routine medical treatment is allowed to lower the blood pressure below these limits)
* Manifest or recent bacterial endocarditis, pericarditis
* Manifest or recent acute pancreatitis
* Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial aneurysm, arterial/venous malformations
* Neoplasm with increased bleeding risk
* Manifest severe liver disease including hepatic failure, cirrhosis, portal hypertension and active hepatitis
* Major surgery or significant trauma in past 3 months
* Stroke within 30 days
* Life expectancy 6 months or less by judgement of the investigator
* Any condition associated with a significantly increased risk of severe bleeding not mentioned above
* Any contraindication to MRI (e.g. cardiac pacemaker)

Imaging Exclusion Criteria:

* Poor MRI quality precluding interpretation according to the study protocol
* Any sign of intracranial haemorrhage on baseline MRI
* FLAIR showing a marked parenchymal hyperintensity in a region corresponding to the acute DWI lesion indicative of an acute ischemic lesion with a high likelihood of being \> 4.5 hours old
* Large DWI lesion volume \> 1/3 of the MCA or \> 50% of the anterior cerebral artery (ACA) or posterior cerebral artery (PCA) territory (visual inspection) or \> 100 ml
* Any MRI findings indicative of a high risk of symptomatic intracranial haemorrhage related to potential IV-tPA treatment in the judgement of the investigator
C: Inclusion Criteria:

* Informed consent can only be obtained from a patient who according to the trial investigator is mentally capable of decision-making and who, after having received information and got answers to their questions, wants to participate in the trial.
* Brain imaging is compatible with intra cerebral hemorrhage or ischemic stroke.
* Randomization can be performed between 2 and 15 days after stroke onset and by the research group at the patient's local/emergency hospital.
* Persisting focal neurological deficit is present at the time of randomization severe enough to warrant treatment from the physicians and the patient's and relative's perspective.

Exclusion Criteria:

* Subarachnoidal hemorrhage except where secondary to a primary intracerebral hemorrhage.
* Unlikely to be available for follow up for the next 12 months e.g. no fixed home address.
* Unable to speak Swedish and no close family member available to help with follow up forms.
* Other life threatening illness (e.g. advanced cancer) that will make 12-month survival unlikely.
* History of epileptic seizures.
* History of allergy or contraindications to fluoxetine including: Hepatic impairment (S-ASAT/ALAT \> 3 upper normal limit) and renal impairment (S-Creatinine levels \> 180 micromol/L).
* Pregnant or breastfeeding, women of childbearing age not taking contraception. Minimum contraception is an oral contraceptive. An HCG-test is to be made prior randomization and after the end of trial medication.
* Previous drug overdose or attempted suicide.
* Already enrolled into a CTIMP.
* Current or recent (within the last month) depression requiring treatment with an SSRI antidepressant.

Current use of medications which have serious interactions with fluoxetine Use of any mono-amino-oxidase inhibitor (MAOI) during the last 5 weeks. Co-administration of Fluoxetine and a mono-amino-oxidase inhibitor (MAOI) may result in life threatening interactions. Therefore, patients on MAOI are ineligible for the EFFECTS trial. Also, any patient in need of treatment with a MAOI must stop their trial treatment for at least 5 weeks before commencing the MAOI, or to be treated as in-patients by a psychiatrist.
D: Inclusion Criteria:

* Between the ages of 22-85 years old
* Radiographic evidence of acute or subacute stroke
* Ischemic stroke diagnosed within the last 2 weeks to 6 months
* HAMD depression score 8 or greater
* Able to provide written informed consent
* Agree to participate in all study procedures

Exclusion Criteria:

* Metallic objects or neurostimulators implanted intracranially
* Stroke in the area of stimulation
* Current thoughts of SI or self-harm as assessed by the M.I.N.I. Suicide Scale score \> 8
* ASRM (Altman Self Rating Mania Scale) score \> 6 (6 or above indicates likelihood of manic symptoms)
* Current use of illicit substances
* Known history of epilepsy or seizure disorder
* Clinically significant EKG abnormalities including QTC prolongation \>450 ms in men or \>480 ms in women

Answer: A