The Importance of

Neurorehabilitation in the Pursuit

of Neurovascular Excellence

SAMIR R. BELAGAJE, MD FAAN

OCTOBER 13, 2017

Disclosures

I have no commercial interests to disclose

Will discuss some off-label indications for medications such as SSRIs

Objectives

What are the 3 main ways a patient recovers from a stroke

What is neuroplasticity?

Name 3 meds which can be used to help with the recovery process

How does depression affect stroke recovery

Stroke in Perspective

Over 750,000 strokes per year

Fourth leading cause of death in U.S.

Leading cause of permanent disability

Cost exceeds $30 billion/year in U.S.

2/3 stroke survivors receive rehabilitation

The Traditional Model of

Stroke Care in the Hospital

Admission Evaluation/

Mgmt Disposition/D/C

Rehabilitation

Stroke Care is A Spectrum

Multiple phases with different specialists and goals of care

To optimize neurovascular excellence, must optimize care in each

phase

The Rehabilitation Phase

Recovery From Deficits Caused by Stroke

Adapting to Deficits Caused by Stroke

Usually More Chronic and usually the longest phase of stroke

Accomplished by Therapists, Rehabilitation specialists, but not

limited to them!

Caregiver involvement

Rehabilitation of Stroke: The Problem

• Compared to stroke onset, repair to brain cells takes much, much longer (days to

weeks to months…even years)

Repair and recovery is often incomplete

- 30% stroke survivors report some sort of activity restriction 4 years post-stroke

No proven ways to fix or replace brain tissue

People often plateau in their recovery

BOTTOM LINE: No proven guaranteed method

Future Model of Stroke Care in

The Hospital

Admission Evaluation

/Mgmt Disposition/D/C

Rehabilitation

Why Should We Care About

Rehabilitation in Stroke?

Ties Between the Phases

Improve Overall Outcomes in Patients

Medical Economics

Why Should We Care?- Medical

Economics

Reimbursement

- Changing Face of Medicine

Reduce complications

Affect Length of Stay

Adaptive

- Can be harmful (i.e. learned disuse)

Regeneration

- Preservation of penumbra

- Restitution of diaschisis

- Stem cells

* Rewiring (AKA Neuroplasticity)

Methods by Which The Brain

Recovers from A Stroke

Can be personal (learning to eat with another hand instead of using

hemiplegic hand)

Can involve assistive devices (e.g. cane, shower chair, prisms in

glasses for diplopia)

Learned disuse- can be maladaptive

- basis of constraint-induced therapy

Adaptation

Stem Cells, Growth factors

Shown to exist in adult brains of rats

- Migrate from subventricular zone in response to acute ischemic

injury to site of injury

- Multiply like crazy then die off

Application to humans is hot bed of research

Regeneration

Def. of Neuroplasticity-

Re-organization of nervous

system connections through

experience.

Conceptually-

Strengthening of previous

synapses, formation of new

ones, removal of others

Examples: Memory, Skill

learning (e.g. dribbling a

basketball), Phantom limb

pain

Neuroplasticity

Principles of Plasticity

Demand specific – Use it or Lose it

Task specific

Must be interesting or challenging enough for patient to attend to

Re-learning, not just increased activity

- e.g. in motor recovery, plasticity does not occur because of increased motor activity

After A Stroke…

Note: White Arrow denotes stroke location

Source: Feydy et. al. Stroke, 2002

1= Session 1-2 months post-

stroke

2= Session 2-4 months post-

stroke

3= Session 4-6 months post-

stroke

Source: Feydy et. al. Stroke, 2002

Neuroplasticity at the Molecular Level

Synapses in turn are determined by axonal and dendritic

sprouting

Factors:

* GAP43- linked to sprouting in cortex

* NogoA-inhibitor of axonal sprouting

* Other molecules (e.g. ECM proteins, Myelin-assoc

glycoprotein)

Implications for stroke recovery - All these molecules have been

identified in peri-infarct cortex (Carmichael et. al, 2002)

The Traditional Model of

Stroke Care in the Hospital

Admission Evaluation/

Mgmt Disposition/D/C

Rehabilitation

Following acute hospitalization, stroke survivors are usually sent to

3 different places:

- Home (with or without outpt therapy)

- Acute rehabilitation (AKA IRF AKA Acute rehab)

- Nursing home (AKA SNF AKA subacute rehab)

Acute rehab more intense therapy than SNF

Discharge Disposition-

Rehabilitation

Criteria for IRF/Acute Rehab

Admissions Need for 24 hour nursing care

Interdisciplinary team approach (documented team communication)

Discharge plan (Needs to able to return to community following IRF)

Multiple therapy disciplines (PT, OT and/or ST)

Intensive level of rehab (min. of 3 hours/day at least 5 days/week or in some cases an avg. of 15 hours per week if documented why)

Ability to participate in intensive rehab therapy & make measurable improvement

MD supervision on a daily basis

Outcome & Disposition

Source: Belagaje et. al. J Neurointerv Surg. 2014

Outcomes and Disposition

Only 1/22 (4.5%) patients who were discharged to SNF achieved a 90 day mRS ≤2, compared to 41/92 (44.6%) in the IRF group or 48/51 (94.1%) in the home group (p < 0.001).

For patients discharged with mRS=4, 1/14 (14.3%) showed improvement in SNF group compared to 21/27 (77.8%) in the IRF group (p=0.008). For discharge mRS =5, 5/14 (35.7%) showed improvement in the SNF group compared to 28/37 (75.7%) in the IRF group (p=0.013).

Source:

S. Belagaje, D.C Haussen, J. Saver, M. Goyal, D. Liebeskind, D. Yavagal, T. Jovin, R. Nogueira. The Impact of Post-acute discharge disposition on outcomes in the SWIFT PRIME Trial. Presented at ISC, AAN 2017

Stroke severity

Medical comorbidities

Socioeconomic

- Lack of Insurance

Inability to participate in therapy or tolerate therapy

Reasons Why Patients Don’t Qualify

for Acute Rehab Admissions

Infection-related Encephalopathies (UTIs, Pneumonias)

Toxic encephalopathies (Anxiolytics, Sedatives)

Alterations in sleep-wake cycle

Post-stroke seizures/post-ictal state

Post-stroke depression- (under Dx’ed, 20-40% incidence)

? Neurostimulation from Pharmacological treatment

Inability to participate in therapy

sessions-

Ilustrative Case....

80 year old female with cardioembolic stroke

On hospital day 2, she is evaluated by the therapy teams and found

to be lethargic and participating poorly in the therapy.

Because of her lethargy, the therapy team determines that she is

unable to participate in her three hours of therapy per day and

recommend SNF placement.

A subsequent evaluation by the primary team reveals that she has a

low grade fever, leukocytosis, and an urinalysis suggestive of an UTI.

With antibiotics, she improves over the next 2 days, better able to

participate in her therapy sessions and the discharge

recommendation is upgraded to an IRF.

Future Model of Stroke Care in

The Hospital

Admission Evaluation

/Mgmt Disposition/D/C

Rehabilitation

Medications for Rehabilitation

Can improve outcomes

Also worsen outcomes

Evidence remains mixed currently; no clear guidelines established

Pharmacological Goals:

Neurostimulation

Goal: Improve alertness and wakefulness

Amantadine

Methylphenidate

Goal: Address specific deficits

Memantine or Aricept for aphasia

Sources:

Liepert J. Update on pharmacotherapy for stroke and traumatic brain injury recovery during rehabilitation. Curr Opin Neurol. 2016 Dec;29(6):700-705.

Berthier ML, Pulvermüller F, Dávila G, Casares NG, Gutiérrez A. Drug therapy of post-

stroke aphasia: a review of current evidence. Neuropsychol Rev. 2011 Sep;21(3):302-17.

Pharmacological Goal: Remove or

Minimize The Harmful Meds (AKA The

“Bad Actors”

Benzodiazepines

Dopamine Antagonists

Opioids

Anticholinergics/Antihistaminergic Agents

Why Are These Medications Used In

the Stroke Unit?

Benzos Seizure treatment

Agitation/Delirium

Alcohol Withdrawal

Sleep

Opioids

Pain mgmt

Agitation

Headaches

Why Are These Medications Used In

the Stroke Unit?

Antipsychotic Agents

Agitation

ICU Psychosis

Antihistaminergic Agents

Sleep

GI prophylaxis

The Bad Actors

In some situations, use is indicated – would minimize dosing and stop

when ready

In other situations, use alternative pain meds

- Example: Pain mgmt

- Example: Use PPI instead of H2 blockers to minimize

antihistaminergic agents, particularly with elderly

Post-Stroke Depression

Prevalence = 33%; likely underdiagnosed

Can start at anytime post-stroke

Another study found prevalence to vary over time, peaking

at 3 to 6 months with a subsequent decline at 1 year

Difficult to diagnose- atypical Sx

- Reduced motivation, and loss of confidence

Effects on post-stroke outcomes

Depression has an adverse effect on post-stroke outcomes.

Severity of depression was directly correlated with level of physical, cognitive, and functional impairment.

Impairs the rehabilitation process with increased length-of-stays and slower

progress to rehabilitation goals.

Moreover, significant functional improvement at 3 and 6 months was noted in

stroke survivors with depression if it was reduced by 50%.

Earlier initiation of treatment is associated with the improvement on

outcome.

Antidepressant For Motor Improvement:

FLAME Trial

Chollet et. al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. The Lancet Neurology Vol. 10

(2), Feb 2011: 123-130.

Double-blind, placebo-controlled trial

Fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10

days after the onset of stroke

FLAME trial - Results

Upper extremity functional improvement at day 90 was significantly

greater in the fluoxetine group (adjusted mean 34·0 points [95% CI

29·7—38·4]) than in the placebo group (24·3 points [19·9—28·7];

p=0·003).

SSRI assisted motor recovery independent of its antidepressant

effect

Antidepressants: Implication for

Stroke Practice

Effect 1-2 weeks before effect noticed

Safety demonstrated in stroke and TBI patients

SSRIsbleeding risk

- Drug/drug interactions

Low threshold to start…safe and may even help motor outcomes or

generalized outcomes

Back to the Case….

80 yo F w/ cardioembolic stroke

While in the hospital, therapists report decreased participation in

their sessions and minimal gains. Recommend SNF

Nursing reports patient sleeping more

Family reports poor engagement and change in personality

Primary team suspects post-stroke depression and starts SSRI

After a Stroke…

Modified from: Fregni et. al. Nature Clinical Practice: Neurology,

2007

Other possibilities

Stem cells/trophic factors- studies underway

Stimulation

- Transcranial magnetic stimulation

- Transcranial Direct stimulation

Virtual Reality

Robotics

Stimulation TMS and TDCS

Hummel,

Cohen.

Lancet

Neurology

2006

Summary

What we know:

- Neuroplasticity seems to be the main way the brain recovers from a stroke

- Getting stroke patients who are unable to go home to acute rehab whenever possible

- Depression affects outcomes so important to look for it and treat it

Medications can affect rehabilitation

Future treatments: Stem cells and stimulation may be other interventional ways to help patients with strokes

Anyone involved in stroke care has a potential role to play in neurorehabilitation

Thank You

Questions?

sbelaga@emory.edu