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Nicole Falls, Jorge I. Arango, and P. David Adelson

OBJECTIVE

Medically refractory epilepsy remains a therapeutic challenge when resective surgery is not a practical option and indirect neurostimulation efficacy may be limited. In these instances responsive neurostimulation (RNS) has been used in adults, with good outcomes in most patients. However, the utility of RNS in children and young adults has not been systematically explored. In this study, the authors present a single institution’s experience with RNS in pediatric patients.

METHODS

A single-center retrospective chart review of patients who underwent RNS implantation at Phoenix Children’s Hospital during the 4-year period between January 2018 and December 2021 was performed.

RESULTS

Following evaluation for epilepsy surgery, 22 patients underwent RNS implantation using different anatomical targets depending on the predetermined epileptic focus/network. In the cohort, 59% of patients were male, the mean age at implantation was 16.4 years (range 6–22 years), and the mean follow-up time was 2.7 years (range 1.0–4.3 years). All patients had a preoperative noninvasive evaluation that included MRI, video-electroencephalography, and resting-state functional MRI. Additionally, 13 patients underwent invasive monitoring with stereo-electroencephalography to help determine RNS targets. All patients had variable positive responses with reduction of seizure frequency and/or intensity. Overall, seizure frequency reduction of > 50% was seen in the majority (86%) of patients. There were two complications: one patient experienced transitory weakness and one generator failed, requiring replacement. A patient died of sudden unexpected death in epilepsy 3 years after implantation despite being seizure free during the previous year.

CONCLUSIONS

RNS used in children with medically refractory epilepsy improved seizure control after implantation, with decreases in seizure frequency > 50% from preoperative baseline in the majority of patients. Preliminary findings indicate that functional MRI and stereo-electroencephalography were helpful for RNS targeting and that RNS can be used safely even in young children.

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Brian Appavu, Stephen T. Foldes, and P. David Adelson

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children both in the United States and throughout the world. Despite valiant efforts and multiple clinical trials completed over the last few decades, there are no high-level recommendations for pediatric TBI available in current guidelines. In this review, the authors explore key findings from the major pediatric clinical trials in children with TBI that have shaped present-day recommendations and the insights gained from them. The authors also offer a perspective on potential efforts to improve the efficacy of future clinical trials in children following TBI.

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P. David Adelson, Paul Robichaud, Ronald L. Hamilton, and Patrick M. Kochanek

✓ Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague—Dawley immature rats (17 days old; average weight 38.5 ± 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 ± 0.23 minutes (mean ± standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 ± 3.99 minutes) and SI (20.57 ± 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 ± 1.0 g, 1.2 ± 1.6 g, and −0.6 ± 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 ± 0.7 minutes and 1.27 ± 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 ± 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.

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P. David Adelson, George M. Ibrahim, Erin N. Kiehna, and Chima Oluigbo

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David W. Lowry, Ian F. Pollack, Brent Clyde, A. Leland Albright, and P. David Adelson

✓ The outcomes of 25 pediatric patients who underwent upper cervical or occipitocervical fusion at the authors' institution since 1983 were reviewed. At a mean age of 9 years, the patients presented with spinal instability that was associated with os odontoideum in 11 cases, rotatory subluxation in five cases, odontoid fracture in two cases, atlantooccipital dislocation in two cases, and congenital atlantoaxial instability in five patients, four of whom had Down's syndrome (trisomy 21). Ten children had abnormal findings on neurological examination preoperatively; however, nine experienced improvement or resolution of deficits as of their latest follow-up evaluation (mean 17 months). Fusion was achieved with the first operation in 21 of 25 patients; eventually it was attained in all but one. Four patients exhibited persistent spinal instability after an initial procedure. This was caused by erosion of a multistranded cable through the intact arch of C-2 in two cases, by pin site infection necessitating early halo removal in one case, and by slippage in a halo following a Gallie procedure, which was revised with a Brooks fusion in one case. This series, the largest yet published, shows that with appropriate surgical management, posterior upper cervical fusion in the pediatric population is highly successful. Careful attention to halo pin site care and caution in using multistranded cable in young patients may improve results.

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David W. Lowry, Donna L. B. Lowry, Sarah L. Berga, P. David Adelson, and Michelle M. Roberts

✓ The authors present a case of secondary amenorrhea in a 32-year-old woman found to have noncommunicating hydrocephalus due to aqueductal stenosis. Although the presentation of hydrocephalus with amenorrhea has been previously reported, this association remains rare. After treatment via endoscopic third ventriculocisternostomy, the patient resumed normal menstruation and all hormonal abnormalities have resolved except hypothyroidism. A review of the literature on the etiology of endocrinological disturbances in patients with hydrocephalus is presented.

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David W. Lowry, Ian F. Pollack, Brent Clyde, A. Leland Albright, and P. David Adelson

The outcomes of 25 pediatric patients who underwent upper cervical or occipitocervical fusion at the authors' institution since 1983 were reviewed. At a mean age of 9 years, the patients presented with spinal instability that was associated with os odontoideum in 11 cases, rotatory subluxation in five cases, odontoid fracture in two cases, atlantooccipital dislocation in two cases, and congenital atlantoaxial instability in five patients, four of whom had Down's syndrome (trisomy 21). Ten children had abnormal findings on neurological examination preoperatively; however, nine experienced improvement or resolution of deficits as of their latest follow-up evaluation (mean 17 months). Fusion was achieved with the first operation in 21 of 25 patients; eventually it was attained in all but one. Four patients exhibited persistent spinal instability after an initial procedure. This was caused by erosion of a multistranded cable through the intact arch of C-2 in two cases, by pin site infection necessitating early halo removal in one case, and by slippage in a halo following a Gallie procedure, which was revised with a Brooks fusion in one case. This series, the largest yet published, shows that with appropriate surgical management, posterior upper cervical fusion in the pediatric population is highly successful. Careful attention to halo pin site care and caution in using multistranded cable in young patients may improve results.

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Pawel G. Ochalski, David O. Okonkwo, Michael J. Bell, and P. David Adelson

The authors report on a case of successful reversal of sedation with flumazenil, a benzodiazepine antagonist, in a child following a moderate traumatic brain injury and demonstrate the utility of flumazenil to reverse benzodiazepine effects in traumatically injured children.

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Simona Cotena, Ornella Piazza, and Maria Storti