Autonomic dysfunction syndrome (ADS) is reported in cases of traumatic brain injury (TBI), hydrocephalus, brain tumors, subarachnoid hemorrhage, and intracerebral hemorrhage. ADS is rarely reported without an identified cause. In ADS, altered autonomic activity results in hypertension, fever, tachycardia, tachypnea, pupillary dilation, and extensor posturing. 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.
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. PAID is a syndrome attributed to altered autonomic activity. Clinical manifestations consist of a temperature of 38.5º C, hypertension, a pulse rate of at least 130 beats per minute, a respiratory rate of at least 140 breaths per minute, intermittent agitation, and diaphoresis; these are accompanied by dystonia (rigidity or decerebrate posturing for a duration of at least 1 cycle per d for at least 3 d).
Other issues that can occur because of autonomic dysregulation are electrocardiographic alterations, arrhythmias, increased intracranial pressure (ICP), hypohidrosis, subnormal temperature in flaccid limbs, and neurogenic lung disease. 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.
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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. [1, 2, 3] Cortical areas that influence the activity of the hypothalamus include the orbitofrontal, anterior temporal, and insular regions. 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. The complex interaction of these regions is illustrated by the control of temperature and blood pressure.
The pre-optic area of the hypothalamus contains heat-sensitive neurons. Temperature elevation is met with cooling measures: sympathetic activation of sweat glands is augmented, and sympathetic vasoconstriction is inhibited. Increased antidiuretic hormone (ADH) secretion causes water retention and greater sweating.
Cold is detected by 2 mechanisms; 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. 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. This occurs through shivering, vasoconstriction, pilo-erection, and inhibition of sympathetically induced sweating. Integration of cold sensory input and the warm sensory input from the anterior hypothalamus occurs in the posterior hypothalamus. Pyrogens alter the set point of the hypothalamic control, and raising it promotes fever.
Isolated impairment of thermoregulation after extremely severe brain injury has been reported. In this reported case, episodic elevations in temperature during the summer months were reported. Upon controlled manipulation of the environment, failure to manage temperature elevations was documented. Even paradoxical responses to temperature decreases were noted. Other features of dysautonomia were not described in this case.
The anterior and the posterior hypothalamus interact with the brainstem through multiple feedback loops. The midbrain tegmentum gives rise to descending pathways that inhibit a thermogenic drive from the brainstem. Decerebrating lesions result in hyperthermia in rats. Fever in patients with brain injury is most often due to infection. 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.
In addition, dystonia leads to a hypermetabolic state and further temperature elevations. 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. A facilitation signal is then transmitted to the spinal cord control circuits. 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:
Nucleus tractus solitarius
The orbitofrontal cortex is believed to promote parasympathetic activity and to inhibit sympathetic activity. 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. 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. The fluctuations have been found early in the course of the episodic cases (the second day). In a study by Blackman and colleagues, it was noted that plasma catecholamines were elevated at the time of the blood pressure fluctuations. 
In experimentally induced brain trauma, an elevation of catecholamine and acetylcholine levels have occurred. Hypotension, cardiac arrhythmias, or hypertension can result. Milder brain injuries yield an elevation of acetylcholine levels. More severe injuries yield an elevation of catecholamine levels in magnitudes that are proportional to the severity of injury. Coincidentally, the catecholamine levels are inversely proportional to the Glasgow Coma Scale (GCS; see the Glasgow Coma Scale calculator) scores soon after TBI.
Following brain injury, about 15-33% of patients acutely develop ADS.  Within the population of individuals with severe TBI, dysautonomia syndrome is not more common for any particular subset of GCS scores, nor does the frequency increase according to age, sex, or mode of injury. Neuroimaging has revealed more frequent evidence of diffuse axonal injury (DAI) and brainstem injury in persons who develop dysautonomia.
Autonomic dysfunction is associated with increased morbidity. Although the length of stay in acute services is not different from that of persons without ADS, the length of stay in rehabilitation services is longer on the average. The risk of myocardial infarction (MI) and secondary injury due to hemorrhage or elevated intracerebral temperature is of concern. ADS is also associated with less favorable functional outcomes. 
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