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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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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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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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Simona Cotena, Ornella Piazza and Maria Storti

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P. David Adelson, Eugene A. Bonaroti, Todd P. Thompson, Minhduc Tran and N. Ake Nystrom

Object. The standard techniques for repair of peripheral nerve injuries with neuroma formation are typically suboptimal. To begin to explore alternative techniques, the authors used an established model in rodents by using end-to-side “terminolateral” neurorrhaphies (TLNs) to study alternative grafting techniques. The TLN “jump grafts” bypass a neuroma-in-continuity, hypothetically maintaining functional units within the neuroma to facilitate functional regeneration. Evaluation of the extent and origin of the regenerating fibers within the grafts was also undertaken.

Methods. The right tibial nerve in four adult Sprague—Dawley rats was injured using either a crush or transection technique and compared with four uninjured controls. The contralateral peroneal nerve was immediately harvested for microsurgical repair by using TLN jump grafts in all animals. Following a 3-month recovery, the repaired nerves were evaluated electrophysiologically by using evoked electromyography (EMG). Histological preparation was then performed using dual-fluorescent labeling to study axonal regeneration and origins.

Evoked EMG evaluation confirmed healthy electrical conduction across the repair, which was unchanged after transection of the neuroma, but was abolished after transection of the jump graft, indicating functional neural regeneration across both the proximal and distal TLNs of the jump grafts. Fluorescent tracing analysis confirmed regeneration across both the proximal and distal portion of the jump grafts, demonstrated both motor and sensory neurons as the source of the regenerating fibers, and demonstrated significant numbers of double-labeled cell bodies, indicating that collateral sprouting was the primary source of regenerating fibers.

Conclusions. The authors have preliminarily shown that regeneration occurs both electrophysiologically and histologically with a double-TLN jump graft. Clinically, this method could offer an alternative strategy for the technique and timing of neuroma repair.