EXPLAIN IN DETAIL ABOUT ITS REHABILITATIVE ASPECT ?
A 1 INTRODUCTION
1 Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances.
2 This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the NMDA receptor and AMPA receptor are overactivated by glutamatergic storm.
3 Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions (Ca2+) to enter the cell.
4 Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA.
5 Excitotoxicity is involved in spinal cord injury, stroke, traumatic brain injury, hearing loss (through noise overexposure or ototoxicity), and in neurodegenerative diseases of the central nervous system (CNS) such as multiple sclerosis
Pathophysiology
1 Excitotoxicity can occur from substances produced within the body (endogenous excitotoxins).
2 Glutamate is a prime example of an excitotoxin in the brain, and it is also the major excitatory neurotransmitter in the mammalian CNS.
3 During normal conditions, glutamate concentration can be increased up to 1mM in the synaptic cleft, which is rapidly decreased in the lapse of milliseconds.
4 When the glutamate concentration around the synaptic cleft cannot be decreased or reaches higher levels, the neuron kills itself by a process called apoptosis
5 This pathologic phenomenon can also occur after brain injury and spinal cord injury.
6 Within minutes after spinal cord injury, damaged neural cells within the lesion site spill glutamate into the extracellular space where glutamate can stimulate presynaptic glutamate receptors to enhance the release of additional glutamate.
7 Brain trauma or stroke can cause ischemia, in which blood flow is reduced to inadequate levels.
8 Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid, causing cell death, which is aggravated by lack of oxygen and glucose.
9 The biochemical cascade resulting from ischemia and involving excitotoxicity is called the ischemic cascade.
10 Because of the events resulting from ischemia and glutamate receptor activation, a deep chemical coma may be induced in patients with brain injury to reduce the metabolic rate of the brain (its need for oxygen and glucose) and save energy to be used to remove glutamate actively.
11 (The main aim in induced comas is to reduce the intracranial pressure, not brain metabolism).
12 Increased extracellular glutamate levels leads to the activation of Ca2+ permeable NMDA receptors on myelin sheaths and oligodendrocytes, leaving oligodendrocytes susceptible to Ca2+ influxes and subsequent excitotoxicity
13 One of the damaging results of excess calcium in the cytosol is initiating apoptosis through cleaved caspase processing.
14 Another damaging result of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of mitochondria that opens when the organelles absorb too much calcium.
15 Opening of the pore may cause mitochondria to swell and release reactive oxygen species and other proteins that can lead to apoptosis.
16 The pore can also cause mitochondria to release more calcium.
17 In addition, production of adenosine triphosphate (ATP) may be stopped, and ATP synthase may in fact begin hydrolysing ATP instead of producing it
18 Inadequate ATP production resulting from brain trauma can eliminate electrochemical gradients of certain ions.
19 Glutamate transporters require the maintenance of these ion gradients to remove glutamate from the extracellular space.
20 The loss of ion gradients results in not only the halting of glutamate uptake, but also the reversal of the transporters.
21 The Na±glutamate transporters on neurons and astrocytes can reverse their glutamate transport and start secreting glutamate at a concentration capable of inducing excitotoxicity
22 This results in a buildup of glutamate and further damaging activation of glutamate receptors.
23 On the molecular level, calcium influx is not the only factor responsible for apoptosis induced by excitoxicity.
24 Recently, it has been noted that extrasynaptic NMDA receptor activation, triggered by both glutamate exposure or hypoxic/ischemic conditions, activate a CREB (cAMP response element binding) protein shut-off, which in turn caused loss of mitochondrial membrane potential and apoptosis.
25 On the other hand, activation of synaptic NMDA receptors activated only the CREB pathway, which activates BDNF (brain-derived neurotrophic factor), not activating apoptosis
Exogenous excitotoxins
Exogenous excitotoxins
A ) refer to neurotoxins that also act at postsynaptic cells but are not normally found in the body.
B ) These toxins may enter the body of an organism from the environment through wounds, food intake, aerial dispersion etc
C ) Common excitotoxins include glutamate analogs that mimic the action of glutamate at glutamate receptors, including AMPA and NMDA receptors.
1 - BMAA
A ) The environmentally ubiquitous L-alanine derivative, β-methylamino-L-alanine (BMAA) has long been identified as a neurotoxin which was first associated with the amyotrophic lateral sclerosis/parkinsonism–dementia complex (ALS/PDC) in the Chamorro people of Guam.
B ) The widespread occurrence of BMAA can be attributed to cyanobacteria which produce BMAA as a result of complex reactions under nitrogen stress.
C ) Following research, excitotoxicity appears to be the likely mode of action for BMAA which acts as a glutamate agonist, activating AMPA and NMDA receptors and causing damage to cells even at relatively low concentrations of 10 μM.
D ) The subsequent uncontrolled influx of Ca2+ then leads to the pathophysiology described above.
E ) Further evidence of the role of BMAA as an excitotoxin is rooted in the ability of NMDA antagonists like MK801 to block the action of BMAA.
F ) More recently, evidence has been found that BMAA is misincorporated in place of L-serine in human proteins
MECHANISM OF ACTION
1 Mechanical damage from the primary injury compromises cell membranes resulting in the release of glutamate into the extracellular space.
2 Membrane depolarization due to injury-induced ionic imbalances can enhance vesicular release of glutamate.
3 injury-induced energy depletion can also lead to a failure in extracellular glutamate uptake by ATP-dependent glial glutamate transporters.
PHASES OF NEURONAL DAMAGE
A ) The first phase is characterized by sodium dependent neuronal swelling due to activation of ionotrophic glutamatergic receptors resulting in the opening of sodium channels an influx of Na+ ions (and Ca++ ions) an efflux of K+ ions, which is then followed by delayed calcium dependent neuronal degeneration.
B ) The influx of Na+ ions leads to membrane depolarization, opening voltage-dependent calcium channels, and removing the magnesium block on NMDA receptors causing a greater influx of calcium into the cytosol
C ) Calcium influx is further amplified by alterations in AMPA receptor subunit composition (loss of GluR2 subunits) making them more calcium permeable
D ) In addition to acting on ionotrophic receptors glutamate can also activate group I metabotropic glutamate receptors thereby stimulating opening of voltage-gated calcium channels and further increasing calcium influx
E ) This dramatic influx of calcium combined with energy failure initiates the release of intracellular stores of calcium ions
F ) Excessive intracellular calcium levels trigger the activation of secondary biochemical cascades, which ultimately result in the initiation of programmed cell death and the loss of neurons and synapses in vulnerable brain regions such as the hippocampus producing cognitive dysfunction.
G ) Elevated intracellular calcium initiates many cellular pathways including the activation of phospholipases such as calcineurin (CaN), proteases including calpains, and caspases, transcription factors including c-Fos, c-Jun, and c-myc, nitric oxide synthase (NOS) as well as DNA degrading endonucleases.
H ) The over-activation or overproduction of any of these molecules can lead to the degradation of cytoskeletal components (e.g., dendritic spine loss), mitochondrial dysfunction, oxidative stress, and pro-apoptotic gene activation
B ) REHABILITATION OF TBI
INTRODUCTION
1 - The continuum of rehabilitation for persons with traumatic brain injury is broadly segmented into three stages that follow the initial acute medical intervention.
2 These three stages are: Inpatient, Community Integration, and Lifetime of Care ( viva q )
3 Although they reflect a general progression in rehabilitation, a person with traumatic brain injury does not necessarily proceed through these stages in exact order.
4 Each person’s rehabilitation process is unique to his or her circumstances ( v imp )
A ) Inpatient Rehabilitation
1 - Inpatient rehabilitation generally begins following the medical stabilization of the injury at which time the rehabilitation team assesses the individual’s condition, designs and implements rehabilitation interventions and develops a discharge plan.
2 Inpatient rehabilitation is provided while the individual remains in a hospital or other healthcare facility.
3 Acute Rehabilitation
A ) For individuals with identified TBI (usually more moderate or severe), a period of acute care stabilization occurs within the hospital.
B ) Confusion and fatigue are common, and a broad array of specialists may participate in the evaluation and treatment process.
C ) Individuals who continue to have significant complex health needs or are in a coma, may transition to long term acute care hospitals (LTACs). LTACs specialize in medically complex care, such as ventilator weaning and wound care.
D ) Rehabilitation settings are typically characterized by a treatment team approach to meet the complex needs of the person recovering from TBI.
E ) The team is usually directed by both a physician specializing in rehabilitation medicine, and a case manager or care coordinator who ensures communication with family members, funders and across the various treatment providers.
F ) The rehabilitation team approach allows for focused services delivered by specially trained professionals with knowledge of interventions for TBI related issues.
G ) Further, this approach facilitates communication among team members and allows for rapid sharing of goals for treatment that are tailored to each person’s unique rehabilitation needs.
H ) Most importantly, the person with TBI and their circle of support is the hub of the team.
I ) Although every rehabilitation setting has its own specific structure and team organization, the roles of some of the more common team members in both inpatient and outpatient settings are outlined below.
J ) TBI rehabilitation physicians (physiatrists) specialize in rehabilitation medicine and are responsible for the overall coordination of care both in the inpatient and outpatient settings.
K ) They may provide life long medical and medication management and may work with other physician specialists.
L ) Neuropsychologists address TBI effects on thinking processes, behavior and emotions. The neuropsychologist conducts detailed assessments and delivers behavioral intervention
M ) The overall principle of rehabilitation is for individuals with TBI to incorporate compensation strategies into their lives at the same time as they are trying to improve and recover their functions.
N ) The team approach, where the treatment team members meet directly and frequently with each other to discuss the care plan, facilitates communication among team members and allows for rapid sharing of specific goals for treatment that are tailored to each person’s unique rehabilitation needs.
O ) The needs of the person with TBI and the point along the rehabilitation continuum influence the combination, setting and types of services offered.
P ) Ideally, goals are person-centered, reflecting the unique needs, challenges and priorities of the person served.
Q ) Particularly in post-acute settings, such as community integrated rehabilitation programs, many team members may be working together in a coordinated manner to achieve particular goals.
R ) Consistency and structure are often necessary to effectively address cognitive and behavioral issues, thus the need for a well functioning team is paramount in the TBI rehabilitation setting.
Goals are to:
A ) Stabilize the medical and rehabilitation issues related to brain injury and the other injuries.
B ) Prevent secondary complications. Complications could include pressure sores, pneumonia and contractures.
C ) Restore lost functional abilities. Functional changes could include limited ability to move, use the bathroom, talk, eat and think.
D ) The staff will also provide adaptive devices or strategies to enhance functional independence.
E ) The staff will begin to analyze with the family and the patient what changes might be required when the person goes home.
The Rehabilitation Team
The Physiatrist is the team leader in the rehabilitation program.
1 The physiatrist is a physician specializing in physical medicine and rehabilitation.
2 Physiatrists treat a wide range of problems, including the changes after brain injury.
3 The physiatrist will assess and prescribe the treatment and direct the team.
4 The Neuropsychologist is a key member of the rehabilitation team.
5 The neuropsychologist will assess the patient’s changes in thinking and behavior. Changes could include:
A ) Poor memory
B ) Poor attention and concentration
C ) Poor decision-making
D ) Impulsivity
E ) Disorientation
F ) Language and communication abilities
G ) Inability to speak
H ) Inability to understand when spoken to
Many patients are unaware of the changes in the brain and how those changes affect their daily lives.
I ) A patient may not understand what has happened and may be distraught by being away from home.
J ) Through education and counseling, the neuropsychologist can help assure the patient and the patient’s family.
K ) The Rehabilitation Nurse assists patients with brain injury and chronic illness in attaining maximum optimal health, and adapting to an altered lifestyle.
L ) The Rehabilitation Nurse provides care for the patient on the nursing unit. The focus of nursing care is on:
1 Health maintenance
2 Nutrition
3 Potential for aspiration
4 Impaired skin integrity
5 Bowel and bladder incontinence
6 Impaired physical mobility
7 Impaired or limited ability to take care of self
8 Ineffective airway
9 Sleep pattern disturbance
10 Chronic pain
11 Impaired cognition
12 Impaired verbal communication and comprehension
13 Sexual dysfunction
M ) With traumatic brain injury, the PT’s job is to minimize or overcome paralyzing effects related to the brain injury.
N ) Physical therapists help with transfers to and from the bed when a patient cannot walk alone.
O ) They train a person to begin to walk and move more normally.
P ) FOCUS WILL BE ON -
1 Balance
2 Posture
3 Strength
4 Need for a wheelchair, brace or cane
5 Quality of movement
6 Spontaneous movement
7 Coordination of movement
8 Increased sensation of sensory-motor activities
9 Pain management
Q ) The Occupational Therapist assesses functions and potential complications related to the movement of upper extremities, daily living skills, cognition, vision and perception. OTS help determine, with the patient, the best ways to perform daily living skills including showering, dressing and personal hygiene.
R ) The OT will identify equipment for eating, dressing and bathing.
S ) The OT also will look at skills to prepare the patient for a return to the home. These skills include:
Cooking
Grocery shopping
Banking
Budgeting
Readiness for returning to work by assessing prevocational and vocational skills