Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms

Table 3

Selected compounds under consideration for the treatment of pediatric TBI.

Target	Compound	Putative mechanism of action	Study design	Major findings	Refs
DA	Amantadine, methylphenidate, pramipexole, bromocriptine, or levodopa	DA modulator	Open-label retrospective chart review in youths from MCS/VS in subacute rehabilitation;	(i) Greater rate of improvement of Western Neuro Sensory Stimulation Profile (WNSSP) with treatment than without	[44]
	Pramipexole or amantadine	DA modulator	Randomized, double-blind, 8-week trial in youths from MCS/VS at least 1 month after injury;	(i) Greater rate of improvement of Coma/Near Coma scale, WNSSP, and Disability Rating Scale with treatment than without; (ii) No difference in efficacy between amantadine and pramipexole	[45]
	Amantadine	DA modulator	Retrospective, case-controlled trial in youths with TBI;	(i) Subjective improvements noted in 29 of the 46 patients (63%) whose full charts were available for review; (ii) Greater improvement in Ranchos Los Amigos level during admission compared to control group	[46]
	Methylphenidate	DA-norepinephrine reuptake inhibitor	Randomized, double-blind, placebo-controlled crossover trial in youths with chronic mild to severe injury;	(i) No effect on behavior, attention, memory, or processing speed	[47]
ACh	Donepezil	AChEI	ABA trial in adolescents with severe TBI;	(i) Improvement in tests of memory in all subjects (Total Recall, Long-Term Storage, Consistency of Long-Term Retrieval, Delayed Recall).	[48]
Ion channel	Levetiracetam	Presynaptic calcium channel blocker; unknown	Phase II trial in children after TBI with follow-up for two years;	(i) No higher incidence of infection, mood changes, or behavior problems among treatment subjects compared to observation subjects; (ii) One subject in treatment group developed posttraumatic epilepsy (defined as seizures > 7 days after trauma); (iii) Most common adverse events were headache, fatigue, drowsiness, and irritability	[49]
	Phenytoin	Voltage gated sodium channel blocker	Randomized, double-blind, placebo-controlled trial in children after TBI;	(i) No significant difference in percentage of children having seizures in treated and placebo groups	[50]