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?

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

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

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

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

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

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

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

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

HTNDMIICarotid artery stenosisAfibSmoker: 1 pack/day x 30 years +

MedicationsMr. M’s Medications Upon Admission

Medication Name Drug Type Uses Effect on CNS & Mechanism of action

Levetriracetam (Keppra) AED Seizure Inhibitory: Binds to a synaptic vesicle protein, SV2 and

slows nerve conduction across synapses

Divalproex (Depakote) AED Seizure Inhibitory: 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) Statin lower cholesterol none

Carvedilol (COREG) Beta blocker decrease HR none

Clopidogrel (Plavix) Antiplatelet reduce blood

clots

none

Ranitidine (Zantac) H2 receptor antagonist GERD none

Mr. M’s Medications Upon Evaluation

Medication Name Drug Type Uses Effect on CNS & Mechanism of action

Divalproex (Depakote) AED Seizure Inhibitory: Enhances neurotransmission of GABA

Lorazepam (Ativan) Benzodiazepine Acute seizure, sedative,

muscle relaxant

Inhibitory: Enhances neurotransmission of GABA

Haloperidol (Haldol) Antipsychotic schitzophrenia, IAMS Inhibitory: Dopamine antagonist

Famotidine (Pepcid) H2 receptor antagonist GERD none

Lisinopril (Prinivil) Ace Inhibitor HTN, CHF none

Prior Level of Function

(Gleaned from family due to aphasia/decreased cognition)

Mod I with hemi WC for household distancesMod I with WC<>bed/toilet transfersMod I with basic ADLs

Toileting, prepared spaghettios, upper body dressing

Walked short distances with HHA of daughterCould asc/desc 6 STE with unilateral hand rail &

HHA Only left house for doctor’s appointments

Daughter assisted with complex ADLs

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 LStrength: 2/5 for most RUE and LE testing, L:

WFL Sensation: Allodynia to light touch C6-8, L2-S2 *Coordination: RUE impairedProprioception: n/t due to aphasiaDTR: slightly increased on R (2+ vs 1+ on L)

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

FIM Motor Subset PreEating 5Grooming 3Bathing 2Upper Body Dressing 2Lower Body Dressing 1Toileting 1Transfer (toilet) 2Bladder Mgmt 5Bowel Mgmt 5Shower transfer 2Transfer (bed>wheelchair) 1Gait (Walk) 0Stairs 0TOTAL 29

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: ?????

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

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.

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

Purpose

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

Intervention

90 minutes of PT, 60 min OT, 30 min ST/dayLOS: 12 daysFoundations 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

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

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

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 Skills Pre Post

Eating 5 5

Grooming 3 2

Bathing 2 3

Upper Body Dressing 2 5

Lower Body Dressing 1 4

Toileting 1 2

Transfer (Toilet) 1 4

Bladder Mgmt 5 6

Bowel Mgmt 5 6

Shower Transfer 2 4

Transfer (bed>wheelchair) 2 4

Gait (walk) 0 2

Stairs (up to 8 stairs) 0 2

TOTAL 29 49

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.

Cost

CPT Code Procedure Cost Units billed Total Unit Cost

97001 Initial Evaluation $73.13 1 73.13

97112 Neuromuscular Reeducation $31.27 11 343.97

97110 Therapeutic Exercise $29.99 24 719.76

97116 Gait Training $26.70 11 293.7

97530 Therapeutic Activity $32.84 24 788.16

Total Cost: $2,218.72

12 days of therapy x 90 minutes/day = EXPENSIVE!

Medicare A & B covered costs

Would I pay out of pocket?

NO!

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

Discussion

12 day LOS too short? Other intensive RTT protocols demonstrated

successful results after only 10 days. Fritz et al, 201118

Many CIMT protocols are often 2-3 weeks Lin, 2008: 3 weeks19

Huseyinsinoglu, 2012: 10 days20

Could cognitive deficits have impacted the intensity of practice? Most RTT and CIMT exclude pts with “severe”

cognitive deficitsRole of medication?

Impaired motor learning?

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.

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 trainingCollaborated more with social worker

Home health

Appropriate Resources

SNF informationRespite: http://www.harmonychicago.com/contact

Adult day care: http://emeritus86.reachlocal.net/sem/chicago?track=RESPITE

Smoking cessation resourcesOak Park Vet Center

155 South Oak Park Avenue  Oak Park, IL 60302(708) 383-3225

http://saveourvets.com/page4.html

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?

References

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Neurorehabil Neural Repair 2006 20:243.3. Roger VL, et al. Heart disease and stroke statistics- 2011 update: a report from the American Heart Association. Circulation.

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