DISCUSS IN DETAIL THE AUTONOMIC COMPLICATIONS IN TBI ?
OR
DISCUSS BRIEFLY ON PAID SYNDROME ?
OR
ELABORATE IN DETAIL REGARDING ADS ?
A 1 INTRODUCTION / DEFINITION
1 Autonomic dysfunction syndrome (ADS) is reported in cases of traumatic brain injury (TBI), hydrocephalus, brain tumors, subarachnoid hemorrhage, and intracerebral hemorrhage.
2 ADS is rarely reported without an identified cause.
3 In ADS, altered autonomic activity results in hypertension, fever, tachycardia, tachypnea, pupillary dilation, and extensor posturing.
SO , In an effort to more precisely characterize this syndrome, two other terms for it—paroxysmal autonomic instability with dystonia (PAID) and paroxysmal sympathetic hyperactivity—have come into use.
1 PAID occurs as a result of severe brain injury (Rancho level ≤IV) from multiple causes, including traumatic brain injury (TBI), hydrocephalus, brain tumors, subarachnoid hemorrhage, and intracerebral hemorrhage.
2 PAID is a syndrome attributed to altered autonomic activity ( VV IMP )
A ) Clinical manifestations consist of a -
1 temperature of 38.5º C
2 hypertension
3 a pulse rate of at least 130 beats per minute
4 a respiratory rate of at least 140 breaths per minute
5 intermittent agitation
6 diaphoresis
7 these are accompanied by dystonia (rigidity or decerebrate posturing for a duration of at least 1 cycle per d for at least 3 d).
8 Other issues that can occur because of autonomic dysregulation are -
A ) electrocardiographic alterations
B ) arrhythmias
C ) increased intracranial pressure (ICP)
D ) hypohidrosis
E ) subnormal temperature in flaccid limbs, and neurogenic lung disease.
9 Usually episodic, PAID first appears in the intensive care setting but may persist into the rehabilitation phase for weeks to months after injury in individuals who remain in a low-response state ( VV IMP )
10 Neuroimaging has revealed more frequent evidence of diffuse axonal injury (DAI) and brainstem injury in persons who develop dysautonomia.
PATHOPHYSIOLOGY
1 The cause of ADS is dysregulation of the autonomic nervous system (ANS) due to injury to 1 or more parts of the brain that contribute to the ANS.
A ) Cortical areas that influence the activity of the hypothalamus include the orbitofrontal, anterior temporal, and insular regions.
B ) Subcortical areas that influence the hypothalamus include the amygdala (particularly the central nucleus), the peri-aqueductal gray, the nucleus of the tractus solitarius, the cerebellar uvula, and the cerebellar vermis.
------ Damage to these areas releases control of vegetative functions and results in dysregulation of overall autonomic balance.
1 AsThe complex interaction of these regions is illustrated by the control of temperature and blood pressure.
2 The pre-optic area of the hypothalamus contains heat-sensitive neurons.
A ) Temperature elevation is met with cooling measures -
1 sympathetic activation of sweat glands is augmented
2 sympathetic vasoconstriction is inhibited
3 Increased antidiuretic hormone (ADH) secretion causes water retention and greater sweating.
B ) Cold is detected by 2 mechanisms
1 - initially, a decreased rate of firing of the pre-optic heat-sensitive neurons is interpreted as a sensation of cold, and activation of specific cold receptors also ensues.
2 - Sensations of cold are carried to the posterior hypothalamus by the spinothalamic tract, and the sympathetic nervous system is then stimulated to produce increases in body temperature.
A ) This occurs through shivering, vasoconstriction, pilo-erection, and inhibition of sympathetically induced sweating.
B ) Integration of cold sensory input and the warm sensory input from the anterior hypothalamus occurs in the posterior hypothalamus.
C ) Pyrogens alter the set point of the hypothalamic control, and raising it promotes fever.
C ) Isolated impairment of thermoregulation after extremely severe brain injury has been reported.
1 - In this reported case, episodic elevations in temperature during the summer months were reported.
2 - Upon controlled manipulation of the environment, failure to manage temperature elevations was documented.
3 - Even paradoxical responses to temperature decreases were noted.
D ) The anterior and the posterior hypothalamus interact with the brainstem through multiple feedback loops.
E ) The midbrain tegmentum gives rise to descending pathways that inhibit a thermogenic drive from the brainstem.
F ) Decerebrating lesions result in hyperthermia in rats.
G ) Fever in patients with brain injury is most often due to infection.
H ) Less frequently, fever is due to deep venous thrombosis (DVT) or is caused by medications, and even less frequently, fever results from impaired autonomic regulation due to the injury.
I ) In addition, dystonia leads to a hypermetabolic state and further temperature elevations.
1 - The proposed mechanism for this occurs when lesions in the midbrain block interfere with normal inhibitory signals to the pontine and vestibular nuclei, thus making them tonically active.
2 - This results in a hyperexcitable spinal reflex that can be evoked by sensory input signals that have thresholds below those required for motor excitation.
---------Blood pressure is controlled by the interaction of the following cortical and subcortical areas of the brain:
1 Hypothalamus
2 Thalamus
3 Amygdala
4 Orbitofrontal cortex
5 Nucleus ambiguus
6 Nucleus tractus solitarius
7 The orbitofrontal cortex is believed to promote parasympathetic activity and to inhibit sympathetic activity.
8 Dysregulation occurs when these areas are damaged; it causes a cortically provoked release of adrenomedullary catecholamines during ADS episodes, resulting in increased blood pressure, tachycardia, and tachypnea.
9 The previous cases of episodic elevations of blood pressure after TBI contrast with the more constant and persistent hypertension that frequently develops but remains consistent with ADS.
10 In experimentally induced brain trauma, an elevation of catecholamine and acetylcholine levels have occurred. Hypotension, cardiac arrhythmias, or hypertension can result.
A ) Milder brain injuries yield an elevation of acetylcholine levels.
B ) More severe injuries yield an elevation of catecholamine levels in magnitudes that are proportional to the severity of injury.
Vv imp - C ) Coincidentally, the catecholamine levels are inversely proportional to the Glasgow Coma Scale (GCS; see the Glasgow Coma Scale calculator) scores soon after TBI.
11 ADS usually occurs in the setting of severe TBI associated with DAI.
12 ADS must be distinguished from other syndromes presenting similarly; a diagnosis of ADS is one of exclusion, because there are no pathognomonic tests or findings.
MEDICATIONS IN GENERAL
1 The effectiveness of chlorpromazine and bromocriptine (a dopamine antagonist and a dopamine agonist, respectively) in the treatment of ADS illustrates the complexity of the neurotransmitter regulation pathways and the variability of the lesions that can cause the syndrome.
2 Propranolol, a lipophilic beta blocker, has successfully been used to control ADS.
3 Beta blockade has been shown to decrease hypertension and hemodynamic abnormalities.
A ) Beta blockade does not alter diaphoresis, which is mediated via sympathetic cholinergic neurons.
B ) As with all beta blockers, use caution when using in patients with diabetes and asthma.
4 Clonidine has been effective in normalizing plasma epinephrine and in reducing plasma norepinephrine levels, effectively decreasing blood pressure. Alpha-adrenergic and beta-adrenergic blockers prevent electrocardiographic changes and cardiac arrhythmias associated with TBI. However, clonidine is known to cause sedation.
5 Bromocriptine has been used to help combat the hyperthermia and diaphoresis that occur with ADS.
6 Dantrolene has been a useful treatment for extensor posturing but has shown minimal effect against other components of ADS.
7 Morphine has been effective in abolishing ADS, as has naltrexone.
8 Gabapentin has been found to be effective in controlling the autonomic symptoms and the dystonic posturing of ADS.
A ) ROLE OF BETA BLOCKERS
1 - May block effect of vasodilators
2 decreasing platelet adhesiveness and aggregation
3 stabilizing the membrane
4 increasing the release of oxygen to tissues.
5 Beta blockers oppose the multisystemic effects of excessive adrenergic tone.
B ) ROLE OF DOPAMINE AGONISTS
1 Inhibit noxious input to spinal cord.
A ) Bromocriptine
1 Central dopamine excess and central dopamine insufficiency are viewed as contributing to dysregulation of autonomic pathways.
2 Agonists or antagonists may be helpful in treating ADS.
B ) Chlorpromazine
1 Mechanisms include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS.
2 Blocks alpha-adrenergic receptors and depresses release of hypophyseal and hypothalamic hormones.
3 As a rule, however, dopamine antagonists are avoided in patients with TBI
C ) Muscle relaxants
1 Modulate muscle contractions.
Dantrolene
A ) Stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond the myoneural junction and by acting directly on muscle itself.
B ) Most patients respond to 400 mg/d or less.
D ) Opioids
1 - Pain control is essential to quality patient care.
2 - Analgesics such as opioids ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained trauma or injuries.
A ) Morphine
Opioid receptor system is involved in the regulation of central autonomic pathways. ADS has been found to be responsive to narcotics.
As a rule, however, narcotics and other sedating medications are avoided in patients with TBI.
B ) Naltrexone
1 - Cyclopropyl derivative of oxymorphone that acts as a competitive antagonist at opioid receptors.
2 - ADS has been found to be responsive to naltrexone.
E ) Anticonvulsants
These agents terminate clinical and electrical seizure activity of the brain.
1 - Gabapentin
A ) Is a Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-amino butyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors
B ) Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels.