Management of complex pediatric and adolescent spinal deformity.

OBJECT: The authors sought to analyze prospectively the outcome of surgery for complex spinal deformity in the pediatric and young adult populations. METHODS: The authors evaluate all pediatric and adolescent patients undergoing operative correction of complex spinal deformity from December 1997 through July 1999. No patient was lost to follow-up review (average 21.1 months). There were 27 consecutive pediatric and adolescent patients (3-20 years of age) who underwent 32 operations. Diagnoses included scoliosis (18 idiopathic, five nonidiopathic) and four severe kyphoscoliosis. Operative correction and arthrodesis were achieved via 21 posterior approaches (Cotrel-Dubousset-Horizon), seven anterior approaches (Isola or Kaneda Scoliosis System), and two combined approaches. Operative time averaged 358 minutes (range 115-620 minutes). Blood loss averaged 807 ml (range 100-2,000 ml). Levels treated averaged 9.1 (range three-16 levels). There was a 54% average Cobb angle correction (range 6-82%). No case was complicated by the patient's neurological deterioration, loss of somatosensory evoked potential monitoring, cardiopulmonary disease, donor-site complication, or wound breakdown. There was one case of hook failure and one progression of deformity beyond the site of surgical instrumentation that required reoperation. There were 10 minor complications that did not significantly affect patient outcome. No patient received undirected banked blood products. There was a significant improvement in cosmesis, and no patient experienced continued pain postoperatively. All patients have been able to return to their preoperative activities. CONCLUSIONS: Compared with other major neurosurgical operations, segmental instrumentation for pediatric and adolescent spinal deformity is a safe procedure with minimal morbidity and there is a low risk of needing to use allogeneic blood products.

Early onset of leptomeningeal cyst with severe brain herniation: report of two cases.

Leptomeningeal cyst as a rare complication of skull fracture in children is well documented. Most cases occur months or years after the original skull fracture, with characteristic roentgenogram findings. The authors report two cases of leptomeningeal cysts in children less than two years old. The association of hygroma, severe brain injury, increased ICP, and early development of leptomeningeal cyst are discussed. Both patients sustained parietal diastatic skull fracture and developed external brain herniation within 10 days after motor vehicle accidents. Clinically they presented with seizure, hemiparesis, and an enlarging subgaleal mass over the skull fracture. MRI demonstrated severe underlying brain contusion, hygroma around the fracture site, and brain herniation through the skull fracture. Surgical repair of dural laceration and cranioplasty produced good results. The development of hygroma and increased intracranial pressure might account for the early development of leptomeningeal cysts in these two cases.

Pediatric cervical spine fractures: predominantly subtle presentation.

Previous description of cervical spine fractures in children have emphasized high mortality injuries to the upper cervical vertebra. Our experience suggests a much wider spectrum of injury. The medical records of all children with cervical spine fractures admitted to Children's Hospital between January 1, 1985 and December 31, 1989 were reviewed. The average age of the 50 patients was 11 years (range, 2.7 to 18.8 years) and 62% were boys. Motor vehicle-related accidents (54%), sports injuries (18%), and falls (12%) accounted for the majority of the fractures. Twenty-nine patients (58%) had an associated head injury. Fifty percent of the patients were transported from the accident scene and 44% were interhospital transfers. All patients receiving medical care prior to referral had appropriate cervical spine stabilization. On admission 30% of the patients were unresponsive. Thirty-one children were alert and verbal at the time of evaluation and 30 complained of neck pain and tenderness (97%). Twenty-five of the 31 patients (83%) had no demonstrable neurological deficit on initial physical examination. Lateral cervical spine radiographs were diagnostic in 49 children (98%). A relatively even distribution of fractures occurred at all levels of the cervical spine. The anatomic site of the injury did not correlate with age. Sixteen patients (32%) died. Of the 34 who survived, only 6 had a persistent neurological deficit. Children with cervical spine fractures have two distinct patterns of presentation: lethal or intact. The majority of children with cervical spine fractures presented with no complaints of neck pain and/or tenderness need a complete radiographic evaluation of their cervical spine.

Pharmacokinetics, cerebrospinal fluid concentration, and safety of intravenous rifampin in pediatric patients undergoing shunt placements.

The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations and safety of intravenous rifampin in pediatric patients undergoing shunt placement. Nine patients (mean age 5.6 y) received a single dose of rifampin, 20 mg.kg-1, administered intravenously 1 h prior to surgery. The peak serum concentrations ranged from 13.5-26.7 micrograms.ml-1; cerebrospinal fluid concentrations ranged from 0.12-3.0 (mean: 1.4) micrograms.ml-1. The mean total clearance, apparent distribution volume, and elimination half-life were 0.29 l.kg-1.h-1, 1.11.kg-1, and 2.8 h. The concentrations of rifampin achieved in the cerebrospinal fluid exceeded the minimum inhibitory concentrations by 100- to 1000-fold against Staphylococcus epidermidis. However, 5 of 9 patients developed cutaneous reactions during intravenous rifampin prophylactic therapy. Because of the high frequency of adverse effects and more than adequate rifampin concentrations achieved in the cerebrospinal fluid, rifampin doses lower than that used in this study may be evaluated in future studies.

Kynurenate inhibition of cell excitation decreases stroke size and deficits.

Pharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad-spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4-hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p less than 0.001) and improved neurological outcome (p less than 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.

The therapeutic value of nimodipine in experimental focal cerebral ischemia. Neurological outcome and histopathological findings.

Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1, 4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p less than 0.001, p less than 0.01, p less than 0.05 respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p less than 0.01, p less than 0.01, p less than 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the "penumbra" of the ischemic area.

Effect of hypoxia on traumatic brain injury in rats: Part 1. Changes in neurological function, electroencephalograms, and histopathology.

The effect of hypoxia on neurological function, compressed spectral array electroencephalography, and histopathology in head-injured rats was evaluated. By itself, an hypoxic insult (PaO2, 40 mm Hg for 30 minutes) caused no neurological deficit. Twenty per cent of rats injured by a 5-atmosphere temporal fluid percussion impact were hemiparetic contralateral to the side of impact, whereas 80% had no deficit 24 hours after injury. Seventy per cent of rats with both fluid impact injury and hypoxic insult, however, either had a definite hemiparesis, showed no spontaneous movement, or died (P less than 0.02). Impact alone produced an initial depression in electroencephalogram power that was prolonged in rats with hypoxic insult; the most dramatic effect was found in the injured hemisphere, with shorter and less profound effects in the contralateral hemisphere. Perfusion staining of injured cerebral tissue in vivo with 2,3,5-triphenyltetrazolium chloride showed an area of extensive ischemia around the impact site in rats with hypoxic insult. This ischemic area was not present in rats with either impact injury or hypoxia alone. We conclude that posttraumatic hypoxia clearly increases the severity of impact injury in this rat model. These findings suggest that hypoxia, which is common in head-injured patients, very likely worsens the effect of impact injury and may account for much of the diffuse neurological dysfunction in patients with severe craniocerebral trauma.

Effect of hypoxia on traumatic brain injury in rats: Part 2. Changes in high energy phosphate metabolism.

The effect of different degrees of hypoxia on phosphate metabolism in the brains of impact-injured rats was studied using in vivo phosphorus-31 magnetic resonance (P-31 MR) spectroscopy. Sequential changes in P-31 MR spectra within 60 minutes of insult were compared among rats with hypoxia alone, impact injury alone, or a combined impact-hypoxic insult. Hypoxia alone (PaO2 of 40 mm Hg for 30 minutes) caused no remarkable changes in phosphorus spectra except a decrease in intracellular pH. In impact-injured rats, the concentration of inorganic phosphate (Pi) increased, but signals for phosphocreatine (PCr) and beta-adenosine triphosphate (beta-ATP) did not change, and the ratio of PCr/Pi changed only slightly to 7% below control value. When rats with a fluid percussion impact injury of 5 atm were subjected to hypoxic conditions of a PaO2 of 40 mm Hg for 15 minutes, the PCr/Pi ratio decreased by 14%, a value significantly below that of the impact alone group (P less than 0.05). After longer periods of hypoxia (PaO2 of 40 mm Hg for 30 minutes) in impact-injured rats, there were marked increases of Pi and significant decreases in signals for PCr and beta-ATP, which caused a marked decrease in the PCr/Pi ratio to 39% below control values (P less than 0.001). Milder hypoxia (PaO2 of 50 mm Hg for 30 minutes) plus impact injury caused smaller changes in high energy metabolite concentrations, and the PCr/Pi ratio decreased to 15% below control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats.

We have evaluated the use of 2,3,5-triphenyltetrazolium chloride (TTC) as an histopathologic stain for identification of infarcted rat brain tissue. The middle cerebral artery (MCA) of 35 normal adult rats was occluded surgically. At various times after surgical occlusion, rats were sacrificed and brain slices were obtained and stained with TTC or hematoxolin and eosin (H & E); the size of the area of infarcted tissue stained by each method was quantified. In rats sacrificed 24 hr after occlusion of the MCA, the size of the area of infarction was 21 +/- 2% of the coronal section for TTC, and 21 +/- 2% for H & E (mean +/- S.D., N = 13). The size of areas of infarction determined by either staining method was not significantly different in area by the paired test, and a significant correlation between sizes determined by each method was found by linear regression analysis (r = 0.91, slope = 0.89, and the y intercept = 4.4%). Staining with TTC is a rapid, convenient, inexpensive, and reliable method for the detection and quantification of cerebral infarction in rats 24 hr after the onset of ischemia.

Nuclear magnetic resonance imaging and spectroscopy in experimental brain edema in a rat model.

Many aspects of the use of high-resolution nuclear magnetic resonance (NMR) imaging in the examination of brain edema have not been fully explored. These include the quantitation of edema fluid, the ability to distinguish between various types of edema, and the extent to which tissue changes other than a change in water content can affect NMR relaxation times. The authors have compared NMR relaxation times obtained by both in vivo magnetic resonance imaging (MRI) and in vitro NMR spectroscopy of brain-tissue samples from young adult rats with cold lesions, fluid-percussion injury, hypoxic-ischemic injury, bacterial cerebritis, and cerebral tumor. Changes in relaxation times were compared with changes in brain water content, cerebral blood volume, and the results of histological examination. In general, both in vivo and in vitro longitudinal relaxation times (T1) and transverse relaxation times (T2) were prolonged in the injured hemispheres of all experimental groups. Water content of tissue from the injured hemispheres was increased in all groups. A linear correlation between T2 (but not T1) and water content was found. Changes in the values of T1 and T2 could be used to distinguish tumor from cold-injured tissue. Cerebral blood volume was reduced in the injured hemispheres and correlated inversely with prolongation of T1 and T2. The results of this study suggest that, in a clinical setting, prolongation of T2 is a better indicator of increased water content than prolongation of T1, yet quantitation of cerebral edema based solely upon prolongation of in vivo or in vitro T1 and T2 should be undertaken with caution.

Combined magnetic resonance imaging and spectroscopy in experimental regional injury of the brain. Ischemia and impact trauma.

Combined magnetic resonance imaging (MRI) and spectroscopy (MRS) allows unique experimental insights into the central nervous system (CNS) disorders. Clinical applications are forthcoming. In order to address the potential clinical uses of MRI/MRS, experimentally induced focal brain lesions were evaluated with this modality. Focal lesions more closely mirror clinical situations than do global insults, but have rarely been the focus of MRS studies. Fluid-percussion trauma in 48 rats, focal ischemia in 18 rats and in 16 mongrel dogs were produced, with various degrees of severity. A discrepancy between temporal evolution data of MRI and MRS was found: MRI always showed an increase in lesion extension over time while 31P and 1H MRS almost always showed improvement. The severity and evolution of these MRS findings was surprising, and differed from the results reported for global brain injuries. Besides possibly reflecting real improvement in the metabolic state, other explanations for the phenomena exist. Diffusion of inorganic phosphate out of the regional site of injury and its reincorporation for more prominent lactate build-up in regional injury are possible. Therefore the use of MRS to predict metabolic and clinical outcomes of regional brain injury requires methodologic caution, but its combination to MRI offers an unprecedented tool for studies of focal CNS pathology.

Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia.

We evaluated the sensitivity of magnetic resonance (MR) imaging in documenting effects of nimodipine in experimental focal cerebral ischemia. Twenty-five Sprague Dawley rats underwent unilateral occlusion of the middle cerebral artery and were imaged at different intervals thereafter. Neuropathologic and neurologic data were correlated with MR imaging results. Compared with controls, nimodipine-treated rats showed a significantly smaller infarct size (p less than 0.001), as documented by MR imaging and confirmed by neuropathologic evaluations. A less intense signal on the T2 weighted sequence was found in nimodipine-treated rats in basal ganglia (p less than 0.001) and cortex (p less than 0.05). MR imaging may afford unprecedented diagnostic sensitivity in assessing pharmacologic efficacy in cerebral ischemia.

NMR imaging and spectroscopy of experimental brain edema.

A canine model of experimental brain edema utilizing the classic cold lesion technique was used to identify the optimal nuclear magnetic resonance (NMR) spin-echo imaging parameters needed to detect cerebral edema with maximum sensitivity. Each animal was studied with four separate spin-echo sequences, utilizing pulse intervals ranging from 0.5 to 2.0 seconds. The echo delays following each pulse interval were 28 and 56 msec. Cerebral edema was best identified with the longest pulse interval (2.0 seconds), and the second echo delay (56 msec). T1 and T2 relaxation values were obtained from in vitro spectroscopy. The relaxation times were prolonged in the edematous white matter; however, absolute T1 and T2 values proved of little use in comparing different animals.

Outcome from severe head injury in children and adolescents.

A consecutive series of 37 children (17 years old and under) with severe head injury is presented. The data confirm that morbidity and mortality are lower in children than in adults: 51% of these young patients had a good recovery or moderate disability at 6 months. The mortality rate in this series (33%) is higher than in some reports, but probably more closely approximates the death rate from these injuries in an unselected pediatric population than do statistics from tertiary care hospitals. There was no significant relationship between age and outcome in this age group, but mass lesions and uncontrolled intracranial hypertension adversely affected outcome. Diffuse cerebral swelling was commonly seen on computerized tomography scans, and generally was associated with a satisfactory outcome (75%). Two of 13 deaths were considered preventable, emphasizing the narrow therapeutic safety margin and extreme care required in treating these patients.

NMR in experimental cerebral edema: value of T1 and T2 calculations.

In an experimental investigation, the efficacy of nuclear magnetic resonance (NMR) relaxation times in measuring brain water was studied. Cerebral edema was induced in four dogs with a freeze lesion, which was produced by contact with a steel cylinder cooled in liquid nitrogen and placed on the exposed dural surface of the brain. NMR proton imaging was performed 2, 3, 6, or 24 hr after production of the lesion, at a field strength of 0.35 T, using multiparametric spin-echo (SE) technique. The animals were sacrificed immediately after imaging, and brain samples were analyzed for water content (wet-to-dry, microgravimetry). Correlation between water content, NMR imaging, and resulting T1, T2 relaxation times and mobile proton density values calculated with SE technique was performed. Brain sample analysis showed elevation of water content in the white matter subjacent to the lesion in all four dogs, rising at least 15% in each of the animals. NMR imaging detected the freeze lesion and subjacent vasogenic edema of the white matter in all animals. The 2 sec pulse interval SE technique was most sensitive in the detection of the abnormality, and provided optimal differentiation of gray and white matter. The second echo sampling (56 msec) was most sensitive to the detection of edema. The T1 and T2 relaxation values, as well as the mobile proton density values, were elevated in the normal gray matter and in the abnormal white matter when compared with normal white matter in any given animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Proton nuclear magnetic resonance spectroscopy of normal and edematous brain tissue in vitro: changes in relaxation during tissue storage.

Proton nuclear magnetic resonance relaxation times, T1 and T2, of water in unfixed gray and white matter from normal and edematous rabbit brain tissues were measured in vitro at 23 degrees C and 100 MHz to evaluate the effects of the temperature (-25 degrees C to 37 degrees C) and duration (0 to 96 h) of tissue storage on relaxation times. T1 and T2 tended to decrease during storage, probably from slow dehydration of the tissue. This effect was greatest in tissues stored at 37 degrees C and least in those stored at 4 and -25 degrees C; decreases in T1 and T2 were greater in white matter than in gray matter. Freezing brain tissue to -25 degrees C caused a sudden decrease in the T2 of normal white matter. Relaxation times were constant for 5 h in tissues stored at 23 degrees C and for 40 h at 4 degrees C. These results correlated well with corresponding tissue water loss.

Nuclear magnetic resonance studies in normal and edematous brain tissue.

The nmr relaxation rate results show unequivocally that there are at least two fractions of tissue water in both normal and edematous white matter which do not exchange on an nmr time scale (i.e. at times of the order of milli-seconds to fraction of a second). In conjunction with the electron microscopic determination of the extracellular volumes of normal and edematous white matter, the relaxation results can be interpreted in terms of the following model. The two slowly-exchanging water components giving rise to the non-exponential relaxation correspond to cellular and extracellular water; edema changes the relaxation rate of the extracellular component much more than that of the cellular component (the extracellular component becoming more "liquid-like" in its relaxation). Such behavior is consistent with the properties of the extracellular water being due to rapid exchange between motionally restricted water adsorbed at the surface of myelin sheaths, and relatively unrestricted, bulk water. Edema presumably increases the relative amount of the "bulk" water between the axons.