Neuroplasticity Key to recovery after

spinal cord injury

Presented by : Dr. Shamim Khan

RMO, Medical Care Services

CRP, SAVAR

Classification of SCI According to cause :

– Traumatic• Fall from height• Fall while carrying

heavy load• Fall of heavy object• RTA, assault etc.

– Nontraumatic• Tubercular

spondylitis• Pyogenic spondylitis• Spinal cord tumour• Transverse myelitis• GBS

According to site of injury :– Cervical (tetraplegia)– Dorsolumber

(paraplegia)

Classification of SCI (cont.) According to ASIA impairment scale

Complete (A)

Incomplete (B to E)

Spinal shock

This is a time period after the transection of the spinal cord during which all the spinal reflex responses are profoundly depressed.

Duration : Minimum 2 weeks

Bulbocavernous reflex : First reflex to appear following recovery of spinal shock.

Cellular mechanism of SCI Primary injury :

– Membrane dysruption– Vascular damage– Heamorrhage & edema.– Ischemia (lack of O2)

Secondary injury :– Chemical mediators

released by activated macrophage and glial cells

– Prolonged inflammation and scarring.

– Neural cell death and neurological damage.

Why SCI is an irreversible lesion? Once injured, CNS

neurons cannot regenerate their axons, because :– Lack of NGF.

– Inhibition of growth by Oligodendrocytes.

– Clean up activities of lymphocytes and Microglia.

– Increased GABAergic and Glycinergic inhibition of spinal networks.

Neuroplasticity

The ability of the neurons to change their function, chemical profile ( amount and types of neurotransmitters produced) or structure is referred to as neuroplasticity.

The plastic changes in neuron can occur– Physiologically according to activity and skill.– Pathologically due to injury or disease of CNS.

Cortical map of a normal person

Cortical map of a Drummer

Cortical map of a

Football player

Mechanism of Neuroplasticity

in CNS after an injury Acute reorganization

– Unmasking of previously present latent synapses.

Chronic reorganization – Changes in synaptic

efficacy.– Growth of new

synapses by axonal sprouting.

These plasticity changes in CNS can occur at multiple levels like cerebral cortex, brain stem and spinal cord.

Cortical Plasticity

Structural and functional reorganization of cortical representation following injury is known as cortical plasticity.

Cortical plasticity can occur after :– CNS injury (stroke, SCI) – Loss of a body part (amputation of limb or

digit). Changes in cortical map depends on :

– Spared connections available.– Post injury survival time.

Cortical plasticity after arm amputation

In a person with a missing upper limb fMRI and TMS study on somatosensory cortex shows the hand area becomes reorganized for representation of the face.

Cortical plasticity in paraplegic patients

In a complete paraplegic patient after six months or more, extensive use of hands with least or no leg movements results in plastic invasion of cortical hand area on the leg area.

PET scan study demonstrated extension of cortical hand map into the cortical leg map.

Cortical plasticity in paraplegic patients (cont.)

By this way, the upper limb gain strength and lower limbs lose the chance of functional recovery.

And the patient becomes wheelchair bound forever !!

Cortical plasticity

It is desirable in a sense that, increased strength and function of the upperlimbs of paraplegic pt can compensate the weekness of lower limbs for locomotion, bed transfer etc.

It is degradable, because it weakens the chance of lower limbs locomotor recovery.

Is it desirable or degradable ?

Plasticity in transected spinal cord

Reorganization of severed descending pathways of spinal cord can occur over time, and with the aid of regenerative strategies.

1. Regeneration from the severed fibre to the original target.

2. Regeneration through a haphazard pathway.

3. Sprouting from neighbouring fibres onto the denervated target neuron.

4. Enhanced intrinsic plasticity through sensory feedback training.

Plasticity in spinal pathways Role of sensory feedback

training Studies of spinal

reflex conditioning states that, repeated cutaneous or electrical stimulation on paralysed lower limbs can enhance motor response by changing synaptic efficacy along the spinal reflex arc.

Motor tasks can be learned by spinal cord after

transection Can sensory feedback training help spinal

cord to acquire the ability to perform complex motor activity, like walking or stepping?

Several studies on complete thoracic spinal transected cat trained on treadmill for locomotion resulted full weight-bearing stepping.

The spinal cord is able to integrate and adapt to sensory information during locomotor training and in response to sensory feedback, spinal neurons learn to generate stepping in absence of supraspinal input.

Can a complete spinal transected human walk again

? Studies states that, if only 10% of

descending spinal tacts are spared, some voluntary control of locomotion can be recovered.

Task specific locomotor training triggers

spinal cord’s central pattern generator that can sustain lower-limb repetitive movement (walking), independent of direct brain control.

Strategies to enhance recovery of locomotion

Body weight supported treadmill training (BWST).

Pharmacological interventions. Biotechnology to regenerate spinal connectivity.

Body weight supported treadmill training (BWST)

About 50% of patients body weight is suspended in a harness.

Therapists manually assist his legs to step on a slowly moving treadmill.

The aim is to gradually achieve full weight-bearing at increasing treadmill velocities.

BWST !! Light at the end of tunnel Of acutely injured paitents 92% who used wheelchairs became

independent walkers after treadmill training.

Researcher No. of subjects

Durationof injury

Training period

Result

%improved Extent

Dr. Anton Wernig(1995)

44 6 months – 18 yrs

3 – 20 wks

36 independent

Dr. A. L. Hicks(2005)

14 1.2 – 24 yrs

12 – 15 months

Dr. Marcus Wirz (2005)

20 2-17 yrs 8 wks

Pharmacological intervention to improve stepping after SCI Clonidine, a noradrenergic

agonist. Bicuculline, a GABA antagonist. Strychnine, a glycinergic

receptor antagonist. Cyproheptadine, a serotonergic

antagonist.

Molecular Biology and Biotechnologyto regenerate spinal connectivity

Peripheral nerve grafting. Transplantation of fetal nervous tissue. Administration of antibodies that block

growth inhibiting protein activity. Implantation of engineered cells.

Role of Surgical Decompression

and Stabilization Early decompression should be performed to remove the tissue debris, bone and disc that compress the spinal cord to alleviate pressure and to improve the circulation of blood and cerebrospinal fluid.

Some Studies demonstrate that the longer compression of the spinal cord exists, the worse the prognosis for neurological recovery.

Stabilization is obvious for discoligamentus unstable spinal fractures.

Early stabilization allows early mobilization and locomotor training.

Reduce chance of developing pressure sore, postural hypotension and local pain.

Reduce hospital staying period, so reduced chance of acquired infections.