Abbreviations Used Disclosures FMMS: Fugl-Meyer motor scale No financial conflicts to disclose ● FOCUS on the FLAME ● HSS: Hemispheric stroke scale MADRS: Montgomery Asberg depression rating scale ● ● mRS: Modified Rankin Scale SSRI use for post-stroke motor recovery ● NIHSS: National Institute of Health Stroke Scale ● SIS: Stroke Impact Scale ● smRSq: Simplified Modified Rankin Scale Questionnaire Ayesha Araya, PharmD TCA: Tricyclic antidepressant ● PGY-1 Pharmacy Practice Resident Valley Baptist Medical Center-Brownsville Faculty Mentor: Eimeira Padilla-Tolentino, PharmD, PhD 1 2 3 Objectives Patient Case Should fluoxetine 20 mg be added to this patient’s post-stroke management? To understand the rationale for using SSRIs for post-stroke A 50 year old man presented to the ER one week ago. ● ● ● He was diagnosed and treated for an ischemic stroke. A. Yes, the data supports its use for both motor recovery and depression prevention motor recovery The patient is started on aspirin 81 mg and atorvastatin 40 mg daily. B. Yes, but only for depression prevention ● To compare and contrast the FLAME and FOCUS trials ● ● Baseline NIHSS score 8, FMMS total score 52. C. Yes, but only for motor recovery To discuss the potential for SSRIs in post-stroke motor recovery D. No, the data does not support use for neither motor recovery, nor depression prevention ● 4 5 6
What is Stroke? Sequelae of Stroke Types: Stroke survivors are often affected by psychological distress and neuropsychological ● ● ○ Ischemic Stroke disturbances Hemorrhagic stroke ○ ⅓ depression, anxiety, apathy ○ ● Left Brain Background Information Signs and Symptoms ● Paralysis on right side ○ ○ Sudden onset of: ○ Speech/Language Problems Numbness Slow, cautious behavior ■ ○ ■ Confusions ○ Memory Loss ■ Vision changes ● Right Brain ■ Motor ability ○ Paralysis on left side of body ■ Severe headache ○ Vision problems ○ Quick, inquisitive behavior ● Recognition: FAST ○ Memory Loss 1. Ferro JM et al. Nature Reviews. 2016. 1. Frizzell J. AACN Clinical Issues. 2005. 7 2. Urrutia V. Neurology. 2014. 2. Picture from: Willie’s Way Foundation 8 3. Effects of Stroke. ASA. 2019. 9 Motor Recovery Post-Stroke Measuring Stroke Impairment National Institute of Health Stroke Scales (NIHSS) Stroke is the most frequent cause of adult-onset disability in the U.S. General Stroke Impairment Scales: A scale used to objectively quantify the degree of impairment caused by stroke ● ● National Institute of Health Stroke Scale ● The most commonly used scale in the united states Hemiparesis/Hemiplegia: Paralysis on one side of the body European Stroke Scale 11- domains ● ● ● Affects 70-80% of stroke survivors and is often the deficit most in need of rehabilitation ● Modified Rankin Scale ○ Level of consciousness, horizontal extraocular movements, visual fields, facial palsy, left/right arm motor drift, right/left leg motor drift, limb ataxia, sensation. Language/ aphasia, dysarthria, Sense of Permanence: extinction/inattention Specific Neurologic Impairment Scales 20-25% are unable to walk without full physical assistance ● Score of <6 usually indicative of patient recovery, >16 predictive of death ● ● Motor Impairments: Fugl-Meyer Assessment , Motor Assessment Scale, Motricity Index ● ~35% with initial paralysis of the leg do not regain useful function ● Increase of 1 point decreases chance of positive outcome by 17% Balance: Berg Balance Scale ● ● ~65% of patients cannot incorporate the affected hand into their usual activities High degree of reliability and validity ● ● Mobility: Rivermead Mobility Index ● Only 25% return to comparable levels of functioning when compared to non-stroke persons. ● Aphasia: Frenchay Aphasia Screening Test ● Functional scales tend to a plateau of gains by 3 to 4 months after stroke ● Cognition: Montreal Cognitive Assessment 1. Dobkin BH. N Engl J Md. 2005. 1. Winstein CJ, et al. AHA 2016. 1. Wintein CJ, et al. Stroke. 2016. 2. Li. Front Neurol. 2017. 10 2. Goldstein LB, et al. UpToDate. 2019. 11 2. Hinkle JL. Stroke. 2014. 12
Modified Rankin Scale (mRS) Simplified mRS Questionnaire Fugl-Meyer Motor Scale (FMMS) ● Measurement of neurologic disability ○ 0-6 Measuring patient’s baseline of activity Able to live alone without assistance? A method for assessment of motor recovery after stroke ● ● Five domains: Max score of 226 0 No symptoms at all Motor function No ○ Yes 1 Able to carry out all usual duties and activities ○ Sensory function No Balance ○ Able to do everything prior to stroke, Able to walk from one room to another 2 Unable to carry out all previous activities, but able to look after own affair ○ Joint Range without assistance even if slower? without assistance? ○ Joint Pain ● Motor Function Component: Max score of 100/226 points 3 Requiring some help, but able to walk without assistance No No Yes Yes 2 3 ○ 66 points for upper limb, 34 for lower limb 4 Unable to walk and attend to bodily needs without assistance ○ Score of 0 = hemiplegia; 100 = normal motor function ○ <50 Severe, 50-84 marked, 85-94 = moderate, 95-99= slight 5 Bedridden, incontinent and requiring constant nursing care and attention Able to sit up in bed without Validation: Reasonable to measure motor function for stroke patients ● Return to baseline? assistance? 6 Dead Yes No Yes No Validity and reliability: 0 1 4 5 ● Strong test-re-test validity, moderate inter-rater reliabilty 1. Hseih Y, et al. Stroke. 2009. 2. Gladstone DJ, et al. Neurorehabilitation and Neural Repair. r 2002. 1. Banks JL, et al. Stroke. 2007 13 1. Bruno A, et al. Stroke. 2011 14 15 Motor Recovery: The Theory Motor Recovery: Non-Pharmacologic Motor Recovery: Pharmacological Interventions Neural plasticity: The ability of the CNS to ● Non-pharmacological Interventions: Pharmacological Interventions ● ● adapt to changes in the environment or lesions. ○ Rehabilitation ○ Tissue Plasminogen Activator (tPA): given within 4.5 hours → improved recovery post-stroke Biological: Recovery of injured tissue, ○ Activities of daily living (ADLs) Dopamine: May promote neuroplasticity in the cerebral cortex ■ ○ engagement of new uninjured ares, and ■ Strengthening ■ Amantadine: Increased recovery speed during active treatment phase and improved training of other areas to perform new ■ Weight-bearing disability Rating Score (DRS) functions. ■ Joint mobilization ■ Carbidopa/ Levodopa: significant improvement in motor recovery and earlier ability to ○ Behavioral: recovery of function and ■ Manual therapy walk independently limitation of ability to pre-injury level Electric stimulation +/- methylphenidate or amphetamine → no difference ■ ● 1. Sharma N. Handb Clin Neurol. 2013. 1. Sharma N. Handb Clin Neurol. 2013. 2. Oczkowski W. Expert Review of Neurotherapeutics. 2013. 2. Oczkowski W. Expert Review of Neurotherapeutics. 2013. 3. Chollet F, et al. Lancet. 2011. 3. Chollet F, et al. Lancet. 2011. 4. Winstein CJ, et al. Stroke. 2016. 16 17 4. Winstein CJ, et al. Stroke. 2016. 18
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