1. A CASE REPORT BY: MAUREEN SABRI, SPT Does CNS-depressive medication impact the physical therapy prognosis of a 65 year-old patient with chronic stroke receiving intensive, repetitive-task training intervention?

2. What is CNS-depressive medication? Antispastics and antiepileptic drugs (AEDs)  MOA: upregulation of GABA agonists  down-regulation of neuronal excitability by binding to ligand-gated ion channels, which control the flow of chloride into the neuron. 1 Antipsychotics  Often used in management of IAMs and tremor  MOA: block dopamine receptors resulting in a CNS-depressing effect. 1 Interfere with long term potentiation (LTP). 2

3. Review of Common CNS-depressing Meds Common AEDs  Barbituates  Phenobarbitol  Benzodiazepines  Clonazepam, diazepam  GABA analogs  Gabapentin  Fatty acids  Valproic acid Common Antispastics  Baclofen  Benzodiazepines Common Antipsychotics:  Risperidone  Haloperidol or Haldol

4. Q: Why are CNS-depressive meds important in post-stroke PT? CVA is very common in the US  800,000 people a year 3  6 million persons with stroke currently living in the US 4  60% have persistent deficits 5 CNS-depressive meds are commonly prescribed post-stroke  5-20% endure seizure(s) 6  AEDs are the gold standard in treatment  19-39% have spasticity 7,8  Antispastic meds are commonly utilized  72% suffer from pain 9  AEDs, antispastics, tricylic antidepressants are prescribed 23% of the time to treat c/o pain post-stroke 9  3.7% experience Involuntary Abnormal Movements (IAMs) 10  Antipsychotics are the gold standard for treatment

5. Q: Why are CNS-depressive meds important in post-stroke PT? LTP=“Strengthening of excitatory synapses” 6  Ca in post-synaptic cell exceeds threshold  Repetitive stimulation opens NMDA receptors = constitutive activity  Protein synthesis employees.csbsju.edu/.../PSYC340/learning.htm

6. Q: Why are CNS-depressive meds important in post-stroke PT? Repetitive practice of a motor task and/or nerve stimulation has been shown to induce LTP-like plasticity in the motor cortex. 6  Experimental protocol using e-stim, TMS, and MEPs Korchounov & Zeiman 2011: LTP-like plasticity is halted by agonists of dopamine, norepinephrine, and acetylcholine 11  Haloperidol (DA antagonist, antipsychotic)  Prazosine (NE antatonist, antihypertensive)  Biperiden (Ach antagonist, antiparkinsonian agent)  Levetiracetam (an AED, mechanism unknown) 12  GABA antagonists have same effect in rat models, unable to test in humans

7. Q: Why are CNS-depressive meds important in post-stroke PT? A: They may inhibit motor learning. LTP-like mechanisms are critical to motor recovery post-stroke.  Principles of LTP induction include:  Specificity, intensity, duration of stimuli 6  Hmmm…where have we heard these principles before?  LTP=motor learning  Researchers speculate that CNS-depressing drugs will be detrimental to motor learning, memory, and motor re- learning in patients after central legions. 11  No clinical research

8. Background Info 65 yo male retired veteran s/p seizure lasting >45 min due to discontinuation of clonazepam Referred to inpatient rehab with a diagnosis of “generalized weakness” 9 days after admission to ICU. Hospital course included heavy sedation with Ativan due to continuing seizures and agitation in the ICU.  Attempted to treated rather unsuccessfully during acute stay

9. Past Medical History L parietal lobe and basal ganglia stroke (STN)  R UE and LE hemiparesis  R UE spasticity, increased RLE tone  RUE hemiballismus  Seizure disorder (?)  Aphasia  Cognitive deficits HTN DMII Carotid artery stenosis Afib Smoker: 1 pack/day x 30 years +

10. Medications Mr. M’s Medications Upon Admission Medication NameDrug TypeUsesEffect on CNS & Mechanism of action Levetriracetam (Keppra)AEDSeizure Inhibitory: Binds to a synaptic vesicle protein, SV2 and slows nerve conduction across synapses Divalproex (Depakote)AEDSeizureInhibitory: Enhances neurotransmission of GABA Clonazepam (Klonopin)Benzodiazepine Seizure, increased tone Inhibitory: Enhances neurotransmission of GABA Venlafaxine (Effexor)Antidepressant (SNRI) Depression, anxiety Excitatory: Serotonin and norepinephrine agonist Lovastatin (Mevacor)Statinlower cholesterolnone Carvedilol (COREG)Beta blockerdecrease HRnone Clopidogrel (Plavix)Antiplatelet reduce blood clots none Ranitidine (Zantac)H2 receptor antagonistGERDnone Mr. M’s Medications Upon Evaluation Medication NameDrug TypeUsesEffect on CNS & Mechanism of action Divalproex (Depakote)AEDSeizureInhibitory: Enhances neurotransmission of GABA Lorazepam (Ativan)Benzodiazepine Acute seizure, sedative, muscle relaxant Inhibitory: Enhances neurotransmission of GABA Haloperidol (Haldol)Antipsychoticschitzophrenia, IAMSInhibitory: Dopamine antagonist Famotidine (Pepcid)H2 receptor antagonistGERDnone Lisinopril (Prinivil)Ace InhibitorHTN, CHFnone

11. Prior Level of Function (Gleaned from family due to aphasia/decreased cognition) Mod I with hemi WC for household distances Mod I with WC<>bed/toilet transfers Mod I with basic ADLs  Toileting, prepared spaghettios, upper body dressing Walked short distances with HHA of daughter Could asc/desc 6 STE with unilateral hand rail & HHA Only left house for doctor’s appointments Daughter assisted with complex ADLs

12. Examination: Relevant Findings PROM: B knee flexion contractures, R elbow, shoulder, and ankle contractures.  R shoulder flexion & abd: ~90◦  R knee ext: -19, L knee ext: -15  R elbow ext: -75  R ankle dorsiflexion: -5 Similar AROM on R, WFL on L Strength: 2/5 for most RUE and LE testing, L: WFL Sensation: Allodynia to light touch C6-8, L2-S2 * Coordination: RUE impaired Proprioception: n/t due to aphasia DTR: slightly increased on R (2+ vs 1+ on L)

13. Examination: Outcome Measures FIM*  29/91 for motor subset  Transfer: 1  Gait: 0  Stairs: 0 Modified Ashworth:  3/5 for R bicep and R hamstring Mini Mental State Exam  14/30* indicating “severe” cognitive impairment

14. Goals The patient’s: To go home/to be independent The family’s: for the pt to return to his pre-admission level of function to decrease burden of care. The Physical Therapist’s: ?????

15. Areas of Concern Lacking social support:  Family visited once during month-long hospital course  Daughter worked and was not home during the day  Continued smoking  Pt stated that he did not wear pants at home due to difficulty with lower body dressing Prior Falls  Family stated that the patient would fall out of his WC occasionally, but could scoot to the phone to tell his daughter, who would come home to help him up

16. Clinical Impression What was the impact of lacking social support?  Pt’s care was inadequate at home  Perhaps the patient’s immobility is related to lacking resources/opportunity rather than impairment  My goal was to increase the patient’s level of independence beyond his PLOF to improve QOL by reducing dependence on caregivers. What is the impact of the patient’s medication on the patient’s prognosis for motor recovery?  Seizure, hemiballismus and spasticity are all treated with CNS- depressive medication.

17. Clinical Impression Impairments (practice patterns):  Impaired R motor function leading to impaired ROM and coordination (5D)  Deconditioning (6B)  Impaired sensation  skin breakdown (7A)  Impaired cognition Functional limitations:  Unable to independently perform ADLs  Unable to walk/climb stairs  Unable to perform WC<>bed/toilet transfers  Unable to independently navigate his home Participation:  Unable to be an active member in the community  Dependent upon assistance of family members

18. Purpose Does CNS-depressive medication negatively impact this patient’s prognosis for motor recovery?

19. Intervention 90 minutes of PT, 60 min OT, 30 min ST/day LOS: 12 days Foundations of intervention:  Instructed pt to think about what skills are most meaningful to him at home. Encouraged the patient to make lofty goals and think about what skills will increase independence.  The pt identified the following skills to be most meaningful: Transfers (bed<>WC, toilet<>WC) Sit to stand Gait  Repetitive task training (RTT) of these skills with emphasis on intensity of practice

20. Intervention Support for RTT: French et al 2008: systematic review & meta anaylsis comparing RTT to “usual care” 13  Analyzed everything from treadmill training, standing and seated balance training, CIMT  Conclusion: some form of RTT resulted in “modest improvement” across a range of lower limb outcome measures  Effective in chronic stroke Langhorne et al 2009: systematic review of motor recovery after stroke 14  CIMT is best intervention for UE  RTT best for transfer training  High intensity training best for gait

21. Intervention Protocol?  Beyond CIMT and BWSTMT, specific protocol for lower level pts with CVA are difficult to find.  Functional, meaningful practice is patient-specific and hard to quantify Intervention focused upon meaningful skills with the following concepts of motor learning in mind:  Blocked practice (at least 5 min of a task continuously) 15  Varied environments/surfaces  Tapered verbal feedback  Time allowed for processing due to cognitive deficits.  Cardiovascular training: 20 min Nustep or bike/day

22. Results FIM  MCID: 17/91 on motor subset for acute stroke 16  SEM and MDC not established  Valid and reliable for acute stroke, no data on chronic Functional Independence Measure SkillsPrePost Eating55 Grooming32 Bathing23 Upper Body Dressing25 Lower Body Dressing14 Toileting12 Transfer (Toilet)14 Bladder Mgmt56 Bowel Mgmt56 Shower Transfer24 Transfer (bed>wheelchair)24 Gait (walk)02 Stairs (up to 8 stairs)02 TOTAL2949

23. Results Skills:  Transfers: improved from Max A to Min A  Sit>stand improved from Max A to Min A  able to tolerate 1 min independent standing balance between trials.  Gait improved to Max A up to 20’ from “activity does not occur” Pt was discharged below his preadmission level of function.

24. Cost CPT CodeProcedureCostUnits billedTotal Unit Cost 97001Initial Evaluation$73.13173.13 97112Neuromuscular Reeducation$31.2711343.97 97110Therapeutic Exercise$29.9924719.76 97116Gait Training$26.7011293.7 97530Therapeutic Activity$32.8424788.16 Total Cost:$2,218.72 12 days of therapy x 90 minutes/day = EXPENSIVE! Medicare A & B covered costs

25. Would I pay out of pocket? NO!

26. Discussion Multiple poor prognostic indicators:  Chronic stroke  Multiple studies show that gains can be made when intensive PT is employed in chronic stroke. Moore et al, 2010 hypothesized that a “plateau” occurs in PT due to lack of task-specific practice in the clinical setting. 17  Older age  Most patients with CVA are older, 65 is relatively young  Multiple comorbidities  Most patients with CVA have multiple comorbidities  Smoking

27. Discussion 12 day LOS too short?  Other intensive RTT protocols demonstrated successful results after only 10 days.  Fritz et al, 2011 18  Many CIMT protocols are often 2-3 weeks  Lin, 2008: 3 weeks 19  Huseyinsinoglu, 2012: 10 days 20 Could cognitive deficits have impacted the intensity of practice?  Most RTT and CIMT exclude pts with “severe” cognitive deficits Role of medication?  Impaired motor learning?

28. Conclusion Vision 2020:  “doctors of physical therapy, recognized by consumers and other health care professionals as the practitioners of choice to whom consumers have direct access for the diagnosis of, interventions for, and prevention of impairments, activity limitations, participation restrictions, and environmental barriers related to movement, function, and health.” 21 Basic understanding of pharmacology is essential for formulating realistic prognoses.  Communication with MDs and family re: expectations, burden of care, etc.

29. What would I have done differently? Intervention limited by facility  Treadmill Training  Moore 2010 excluded all pts who couldn’t ambulate 10’ independently  Hornby & Straube showing that intensive locomotor training actually translates into improved transfer and balance skills. Adhered to a more specific protocol so the intervention could be replicated Insisted on family training Collaborated more with social worker  Home health

30. Appropriate Resources SNF information Respite: http://www.harmonychicago.com/contact http://www.harmonychicago.com/contact Adult day care: http://emeritus86.reachlocal.net/sem/chicago?track=RESPITE http://emeritus86.reachlocal.net/sem/chicago?track=RESPITE Smoking cessation resources Oak Park Vet Center  155 South Oak Park Avenue Oak Park, IL 60302 (708) 383-3225  http://saveourvets.com/page4.html

31. Questions? Discussion points: Was this patient appropriate for inpatient rehab? Do you consider the patient’s medication list when determining prognosis? Do you think our program needs to incorporate more pharmacology into the curriculum?

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