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Parkinson’s disease (PD) is a progressive, degenerative disease that affects nearly 10 million people worldwide. Hallmark limb motor signs and dopamine depletion have been well studied; however, few studies evaluating early stage, prodromal biology exist. Pink1−/− rats, a rodent model of PD mitochondrial dysfunction, exhibit early stage behavioral deficits, including vocal communication and anxiety, that progress during mid-to-late adulthood (6–12 months of age). Yet, the biological pathways and mechanisms that lead to prodromal dysfunction are not well understood. This study investigated the Pink1−/− rat in young adulthood (2 months of age). Mixed sex groups of Pink1−/− rats and wildtype (WT) controls were assayed for limb motor, anxiety, and vocal motor behaviors. A customized NanoString CodeSet, based on genetic work in later adulthood, was used to probe for the up regulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. In summary, the data show sex- and genotype-differences in limb motor, anxiety, and vocal motor behaviors. Specifically, female Pink1−/− rats demonstrate less anxiety-like behavior compared to male Pink1−/− rats and female rats show increased locomotor activity compared to male rats. Pink1−/− rats also demonstrate prodromal ultrasonic vocalization dysfunction across all acoustic parameters and sex differences were present for intensity (loudness) and peak frequency. These data demonstrate a difference in phenotype in the Pink1−/− model. Tuba1c transcript level was identified as a key marker negatively correlated to ultrasonic vocalization at 2 months of age. Identifying genes, such as Tuba1c, may help determine early predictors of PD pathology in the Pink1−/− rat and serve as targets for future drug therapy studies.

OBJECTIVE Awake craniotomy (AC) is employed to maximize tumor resection while preserving neurological function in eloquent brain tissue. This technique is used frequently in adults but remains poorly established in children. Its use has been limited due to concern for children’s neuropsychological differences compared with adults and how these differences may interfere with the safety and feasibility of the procedure. Among studies that have reported pediatric ACs, complication rates and anesthetic management vary. This systematic review was performed to comprehensively analyze outcomes and synthesize anesthetic protocols of pediatric ACs. METHODS The authors followed PRISMA guidelines to extract studies that reported AC in children with intracranial pathologies. The Medline/PubMed, Ovid, and Embase databases were searched from database inception to 2021, using the terms ("awake") AND ("Pediatric*" OR "child*") AND (("brain" AND "surgery") OR "craniotomy"). Data extracted included patient age, pathology, and anesthetic protocol. Primary outcomes assessed were premature conversion to general anesthesia, intraoperative seizures, completion of monitoring tasks, and postoperative complications. RESULTS Thirty eligible studies published from 1997 to 2020 were included that described a total of 130 children ranging in age from 7 to 17 years who had undergone AC. Of all patients reported, 59% were male and 70% had left-sided lesions. Procedure indications included the following etiologies: tumors (77.6%), epilepsy (20%), and vascular disorders (2.4%). Four (4.1%) of 98 patients required conversion to general anesthesia due to complications or discomfort during AC. In addition, 8 (7.8%) of 103 patients experienced intraoperative seizures. Furthermore, 19 (20.6%) of 92 patients had difficulty completing monitoring tasks. Postoperative complications occurred in 19 (19.4%) of 98 patients and included aphasia (n = 4), hemiparesis (n = 2), sensory deficit (n = 3), motor deficit (n = 4), or others (n = 6). The most commonly reported anesthetic techniques were asleep-awake-asleep protocols using propofol, remifentanil or fentanyl, a local scalp nerve block, and with or without dexmedetomidine. CONCLUSIONS The findings of this systematic review suggest the tolerability and safety of ACs in the pediatric population. Although pediatric intracranial pathologies pose etiologies that certainly may benefit from AC, there is a need for surgeons and anesthesiologists to perform individualized risk-benefit analyses due to the risks associated with awake procedures in children. Age-specific, standardized guidelines for preoperative planning, intraoperative mapping, monitoring tasks, and anesthesia protocols will help to continue minimizing complications, while improving tolerability, and streamlining workflow in the treatment of this patient population.

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