This case report is remarkable because PAID is rarely encountered in patients with cerebral infections. Autonomic dysfunction is reported in cases of traumatic brain injury (TBI), hydrocephalus, brain tumors, subarachnoid hemorrhage, and intra-cerebral hemorrhage. The clinical manifestations of autonomic dysfunction are hypertension, a temperature above 38.5°C, a pulse of at least 130 beats per minute, a respiratory rate of at least 40 breaths per minute, intermittent agitation, and diaphoresis. This constellation of symptoms is accompanied by dystonia (rigidity or decerebrate posturing for a duration of at least one cycle per day for at least three days). This can be attributed to altered autonomic activity and recently a new term has been put forth that seeks to more precisely characterize this condition: paroxysmal autonomic instability with dystonia (PAID) . While PAID is predominantly associated with TBI, infection is seldom considered to be a cause of PAID .
In 1929 Penfield described a patient with a syndrome called "diencephalic autonomic epilepsy". Signs and symptoms consisted of prodromal restlessness, sudden vasodilatation, sudden rise in blood pressure, lacrimation, diaphoresis, salivation, dilatation or contraction of pupils, sometimes protrusion of eyes, increased rate and pressure of pulse, marked retardation of respiratory rate, elicitation of pilomotor reflex, and rarely loss of consciousness. These features were followed by disappearance of superficial blush and fall of blood pressure, slowing and weakening of pulse, hiccupping, transient shivering, and Cheyne-Stokes respiration. Disturbance of hypothalamic function was considered to be due to a focal epileptic discharge. Autopsy revealed a tumor in the third ventricle . However, later reports of diencephalic seizures did not correlate with electroencephalogram seizure activity, nor were they responsive to anti-convulsants [4–6]. Nowadays the "diencephalic seizures" are considered to constitute a syndrome distinct from PAID .
Hereafter, episodic agitation, diaphoresis, hyperthermia, tachycardia, tachypnea, and rigid decerebrate posturing after severe brain injury were first noted in a report by Strich in 1956 . He called these events "brainstem attacks". Subsequently, this constellation of clinical signs has received a variety of labels, including autonomic dysfunction syndrome, dysautonomia, and sympathetic storms . While PAID is noted in approximately 15 to 33% after brain injury, there seems to be no relation with the severity of brain damage. Neuroimaging revealed more frequent evidence of diffuse axonal injury and brainstem injury in those who developed dysautonomia. Often tachycardia, fever and hypertension are the main presenting signs . Our case illustrates this, as extensor posturing was only present in the first days.
The pathophysiology of PAID can be best explained by dysfunction of autonomic centers in the diencephalon (thalamus or hypothalamus) or their connections to cortical, sub-cortical, and brainstem loci that mediate autonomic function, which leads to loss of control of vegetative functions [1, 5]. The episodic nature of dysautonomia in PAID might be related to triggering events . Changes in intra-cranial pressure or stimulation of muscle mechanoreceptors and manipulation of endotracheal tube, oropharyngeal suction, and pain may precipitate these attacks [6, 9–11]. Indeed, our patient had a slightly raised intra-cranial pressure at the second lumbar puncture. Thermoregulatory dysfunction may also be produced by hypothalamic dysfunction as by the hyper-metabolic state that accompanies sustained muscular contractions. Rigidity and decerebrate posturing are seen experimentally and clinically with lesions in the midbrain, which causes blocking of normal inhibitory signals to pontine and vestibular nuclei .
PAID is predominately associated with TBI, but alternative diagnoses should be considered (see Table 2) [10, 12].
All these diseases share some features with PAID. Autonomic dysfunction is associated with increased morbidity. While the length of stay in hospital is not different from those without PAID, the length of stay in rehabilitation services is longer. The risk of myocardial infarction and secondary injury due to hemorrhage or elevated intra-cerebral temperature is of concern. Additionally, PAID is also associated with less favorable functional outcomes.
Treatment of PAID is based on case reports and randomized clinical trials are lacking. Next to the treatment of the underlying cause the central sympathetic pathways may be controlled by morphine, bromocriptine [5, 9, 13, 14], clonidine or a non-selective beta-blocker [6, 13–15]. Benzodiazepines can also be effective, as in our patient [1, 16]. Dantrolene can decrease fever due to prolonged muscle contraction [11, 16].
In this case report PAID was secondary to tuberculous meningitis with infiltration of the thalamus hypothalamus parenchyma. Autonomic instability has only been described once in a two-year-old girl with tuberculous meningitis . However, this girl also had hydrocephalus and bilateral hemorrhagic infarctions in her basal ganglia. Conditions that independently have been associated with PAID. Early recognition is of paramount importance to start treatment in an early stage, but recognition is often difficult, as demonstrated in this case.