Brainstem Injury Research Articles

Feeding and communication impairments in infants with central grey matter lesions following perinatal hypoxic–ischaemic injury

BackgroundBasal ganglia and thalamic (BGT) injury is common after acute perinatal hypoxia–ischaemia. Cerebral palsy is the most obvious consequence of BGT injury affecting 70–75% of survivors and is predictable from neonatal magnetic resonance imaging (MRI). However there is no equivalent predictive data for other specific outcomes. Feeding and communication impairments are also common in children following hypoxic–ischaemic encephalopathy (HIE) and BGT injury. AimsTo describe, in infants with HIE and BGT injury, the prevalence of feeding and communication impairments; and to evaluate the accuracy of early MRI for predicting these outcomes. Methods175 term infants with HIE and BGT injury were studied. Brain lesions were classified by site and severity from the MRI scans. Motor, feeding and communication impairments were documented at 2 years. ResultsFeeding and communication impairments occurred in 65% and 82% of 126 survivors respectively and related strongly to the severity of motor impairment. Forty-one children had a gastrostomy or long-term nasogastric tube. Injury severity in all brain regions was significantly associated with feeding and communication impairment on univariate analysis. On logistic regression analysis BGT (OR 10.9) and mesencephalic lesions (OR 3.7) were independently associated with feeding impairment; BGT (OR 10.5) and pontine lesions (OR 3.8) were associated with gastrostomy; the severity of BGT lesions (OR 20.1) was related to the severity of communication impairment. ConclusionsFeeding and communication impairment are very common in children with BGT and brainstem injury of neonatal origin and can be well predicted from early MRI scans.

Brainstem injury by penetrating head trauma with a knife

The authors describe a rare case about a traumatic lesion of brain and brain stem with a knife. In this case the patient had good clinical condition, diagnosed with TBI by infectious complications. We have highlighted the unusual diagnosis, proximity of vascular structures, the technique used in the treatment and the good outcome of the injury.

Pathological and immunohistochemical study of lethal primary brain stem injuries

BackgroundMany of the deaths that occur shortly after injury or in hospitals are caused by mild trauma. Slight morphological changes are often found in the brain stems of these patients during autopsy. The purpose of this study is to investigate the histopathological changes involved in primary brain stem injuries (PBSI) and their diagnostic significance.MethodsA total of 65 patients who had died of PBSI and other conditions were randomly selected. They were divided into 2 groups, an injury group (25 cases) and a control group (20 cases). Slides of each patient’s midbrain, pons, and medulla oblongata were prepared and stained with HE, argentaffin, and immunohistochemical agents (GFAP, NF, amyloid-ß, MBP). Under low power (×100) and NF staining, the diameter of the thickest longitudinal axon was measured at its widest point. Ten such diameters were collected for each part of the brain (midbrain, pons, and medulla oblongata). Data were recorded and analyzed statistically.ResultsBrain stem contusions, astrocyte activity, edema, and pathological changes in the neurons were visibly different in the injury and control groups (P < 0.05). Characteristic changes occurred in the neural axons, axon diameter varied from axon to axon and even over different segments of one axon, and several pathological phenomena were observed. These included segmental thickening and curving, wave-like processing, disarrangement, and irregular swelling. A few axons ruptured and intumesced into retraction balls. Immunohistochemical MBP staining showed enlargement and curving of spaces between the myelin sheaths and axons in certain areas. The myelin sheaths lining the surfaces of the axons were in some cases incomplete and even exfoliated, and segmentation disappeared. These pathological changes increased in severity over time (P < 0.05).ConclusionsThese histopathological changes may prove beneficial to the pathological diagnosis of PBSI during autopsy. The measurement of axon diameters provides a referent quantitative index for the diagnosis of the specific causes of death involved in PBSI.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1345298818712204

Catastrophic Injuries in Pole Vaulters

Background: A prior review of catastrophic pole vaulting injuries from 1982 through 1998 revealed an average of 2.0 injuries per year, with 69% (1.38 per year) of the injuries secondary to athletes landing off the sides or back of the landing pad and 25% (0.5 per year) from athletes landing in the vault box. In 2003, several rule changes for the sport of pole vaulting were mandated, including enlarging the minimum dimensions of the landing pad. Hypothesis/Purpose: Our goals were to (1) identify the post-2003 rule change incidence and profile of catastrophic pole vaulting injuries through 2011 and compare them, where possible, with the prior incidence and profile and (2) determine, via a questionnaire, the frequency with which pole vaulters land in the vault box. We hypothesized that the new, larger landing pads would reduce the number of catastrophic injuries. Study Design: Descriptive epidemiology study. Methods: We prospectively reviewed all catastrophic pole vaulting injuries (ie, brain hemorrhage; skull, spine, or pelvic fracture; substantial pulmonary or intra-abdominal injury) in the United States from 2003 through 2011, surveyed 3335 pole vaulters to determine the frequency of landing in the vault box, and compared results with those in the literature. Results: From 2003 to 2011, 19 catastrophic injuries occurred (average of 2.1 per year), with the majority (n = 14, 74%, 1.55 per year) landing in or around the vault box. Four (21%, 0.44 per year) injuries occurred when an athlete landed off the sides or back of the landing pad and 1 (5%) when the pole broke. There were 11 (58%) major head injuries (1 fatality), 4 (21%) spine fractures (1 with paraplegia), 2 (11%) pelvic fractures (both with intra-abdominal injuries), 1 (5%) brain stem injury (fatal), and 1 (5%) thoracic injury (rib fractures and pneumothorax). The annual fatality rate fell from 1.0 in the prior study to 0.22 in the current study. According to the pole vaulters survey, during their careers, 77.12% (n = 2572) landed in the vault box 1 to 3 times, 15.92% (n = 531) never landed in the vault box, 6.12% (n = 204) landed in the vault box 4 to 6 times, and 0.84% (n = 28) landed in the vault box 7 or more times. Conclusion: The 2003 rule changes have markedly reduced the number of catastrophic injuries, especially fatalities, from pole vaulters missing the back or sides of the landing pads; however, the average annual rate of catastrophic injuries from pole vaulters landing in the vault box has more than tripled over the past decade and remains a major problem.

Severe Traumatic Head Injury: Prognostic Value of Brain Stem Injuries Detected at MRI

Traumatic brain injuries represent an important cause of death for young people. The main objectives of this work are to correlate brain stem injuries detected at MR imaging with outcome at 6 months in patients with severe TBI, and to determine which MR imaging findings could be related to a worse prognosis. One hundred and eight patients with severe TBI were studied by MR imaging in the first 30 days after trauma. Brain stem injury was categorized as anterior or posterior, hemorrhagic or nonhemorrhagic, and unilateral or bilateral. Outcome measures were GOSE and Barthel Index 6 months postinjury. The relationship between MR imaging findings of brain stem injuries, outcome, and disability was explored by univariate analysis. Prognostic capability of MR imaging findings was also explored by calculation of sensitivity, specificity, and area under the ROC curve for poor and good outcome. Brain stem lesions were detected in 51 patients, of whom 66% showed a poor outcome, as expressed by the GOSE scale. Bilateral involvement was strongly associated with poor outcome (P < .05). Posterior location showed the best discriminatory capability in terms of outcome (OR 6.8, P < .05) and disability (OR 4.8, P < .01). The addition of nonhemorrhagic and anterior lesions or unilateral injuries showed the highest odds and best discriminatory capacity for good outcome. The prognosis worsens in direct relationship to the extent of traumatic injury. Posterior and bilateral brain stem injuries detected at MR imaging are poor prognostic signs. Nonhemorrhagic injuries showed the highest positive predictive value for good outcome.

Chemotherapy administration directly into the fourth ventricle in a nonhuman primate model

The authors hypothesized that chemotherapy infusions directly into the fourth ventricle might potentially play a role in treating malignant fourth ventricular tumors. The study tested the safety and pharmacokinetics of short- and long-term infusions of methotrexate into the fourth ventricle in a new nonhuman primate model. Six rhesus monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In Group I (3 animals), catheters were externalized, and lumbar drain catheters were placed simultaneously to assess CSF distribution after short-term methotrexate infusions. In 2 animals, methotrexate (0.5 mg) was infused into the fourth ventricle daily for 5 days. Serial CSF and serum methotrexate levels were measured. The third animal had a postoperative neurological deficit, and the experiment was aborted prior to methotrexate administration. In Group II (3 animals), catheters were connected to a subcutaneously placed port for subsequent long-term methotrexate infusions. In 2 animals, 4 cycles of intraventricular methotrexate, each consisting of 4 daily infusions (0.5 mg), were administered over 8 weeks. The third animal received 3 cycles, and then the experiment was terminated due to self-inflicted wound breakdown. All animals underwent detailed neurological evaluations, MRI, and postmortem histological analysis. No neurological deficits were noted after intraventricular methotrexate infusions. Magnetic resonance images demonstrated catheter placement within the fourth ventricle and no signal changes in the brainstem or cerebellum. Histologically, two Group I animals, one of which did not receive methotrexate, had several small focal areas of brainstem injury. Two Group II animals had a small (≤ 1-mm) focus of axonal degeneration in the midbrain. Intraventricular and meningeal inflammation was noted in 4 animals after methotrexate infusions (one from Group I and all three from Group II). In all Group II animals, inflammation extended minimally into brainstem parenchyma. Serum methotrexate levels were undetectable or negligible in both groups, ranging from 0.00 to 0.06 μmol/L. In Group I, the mean peak methotrexate level in fourth ventricle CSF exceeded that in the lumbar CSF by greater than 10-fold. Statistically significant differences between fourth ventricle and lumbar AUC (area under the concentration-time curve) were detected at peaks (p = 0.04) but not at troughs (p = 0.50) or at all time collection points (p = 0.12). In Group II, peak fourth ventricle CSF methotrexate levels ranged from 84.62 to 167.89 μmol/L (mean 115.53 ± 15.95 μmol/L [SD]). Trough levels ranged from 0.06 to 0.55 μmol/L (mean 0.22 ± 0.13 μmol/L). Methotrexate can be infused into the fourth ventricle in nonhuman primates without clinical or radiographic evidence of injury. Observed inflammatory and other histological changes had no clinical correlate. This approach may have pharmacokinetic advantages over current treatment paradigms. Further experiments are warranted to determine if fourth ventricular chemotherapy infusions may benefit patients with malignant fourth ventricular tumors.

Limbic encephalopathy and central vestibulopathy caused by mefloquine: A case report

Mefloquine is a 4-methanolquinoline anti-malarial that in recent years has fallen out of favor for use as chemoprophylaxis against infection with chloroquine-resistant Plasmodium falciparum malaria owing in part to growing concerns of side effects and potential neurotoxicity. Despite over 20 years of licensed use, the pathophysiological mechanisms underlying mefloquine's neuropsychiatric and physical side effects and the clinical significance of the drug's neurotoxicity have remained poorly understood. In this report, an adverse reaction to mefloquine chemoprophylaxis is described characterized by prodromal symptoms of anxiety with subsequent development of psychosis, short-term memory impairment, confusion and personality change accompanied by complaints of disequilibrium and vertigo, with objective findings of central vestibulopathy. It is posited that these effects represent an idiosyncratic neurotoxic syndrome of progressive limbic encephalopathy and multifocal brainstem injury caused by the drug. This case provides insights into the clinical significance of mefloquine neuronal gap junction blockade and neurotoxicity demonstrated in animal models, points to recommendations for the management of affected patients including diagnostic considerations and appropriate referrals, and highlights critical implications for the continued safe use of the medication.

A case of left homonymous upper quadrantanopia after inferior petrosal sinus sampling to investigate acromegaly with empty sella

Diagnosing and treating acromegaly are difficult when imaging of the pituitary gland fails to show an adenoma. Inferior petrosal sinus sampling (IPSS) is a useful diagnostic technique that can aid in both the localization of tumors and lateralization within the pituitary gland. However, some severe neurological complications have been reported in the literature, including brain stem injuries, thromboembolism, isolated sixth nerve palsy, and venous subarachnoid hemorrhage. Here, we report a rare complication of left homonymous upper quadrantanopia after inferior petrosal sinus sampling. A 58-year-old woman with a 10-year history of hypertension was referred to our endocrine clinic for evaluation of acromegaly. She presented with macroglossia, prognathism, and acral enlargement of both hands. Her visual field test was normal. An elevated insulin-like growth factor-1 (IGF-1) level of 902 ng/mL and a nadir growth hormone (GH) level of 8.7 ng/mL on the oral glucose tolerance test confirmed the diagnosis of acromegaly. Magnetic resonance imaging (MRI) revealed an empty sella but no evidence of a pituitary adenoma (Fig. 1A). An In-octreotide scan did not show evidence of ectopic or GH-secreting tumor, so we decided to use IPSS to determine the source of pituitary GH

Encephalitis in the Pediatric Population

1. Stephen J. Falchek, MD* 1. *Division of Pediatric Neurology, Alfred I. duPont Hospital for Children/Thomas Jefferson University, Wilmington, DE, and Philadelphia, PA. * Abbreviations: ADEM: : acute disseminated encephalomyelitis CEP: : California Encephalitis Project CNS: : central nervous system CPP: : cerebral perfusion pressure CSF: : cerebrospinal fluid HSV: : herpes simplex virus IVIG: : intravenous immune globulin MS: : multiple sclerosis PCR: : polymerase chain reaction WNV: : West Nile virus Management of encephalitis, which can be fatal, requires understanding of a broad range of causative agents, pathophysiologic mechanisms, clinical syndromes, and outcomes. After completing this article, readers should be able to: 1. Know the many causes of encephalitis, including infectious, parainfectious, and noninfectious disorders. 2. Recognize the clinical features of encephalitis. 3. Be able to conduct a diagnostic investigation of a patient with encephalitis by using clinical and laboratory criteria. 4. Know the anticipated clinical course of different types of encephalitis. 5. Be familiar with the modalities used to treat encephalitis. 6. Understand the factors that influence the outcome in a patient who has encephalitis. The broad definition of the term “encephalitis,” that is, inflammation of the brain , necessitates acknowledgment of the enormous inclusivity of the topic. The most common interpretation of the term implies a direct invasion of the brain by an infectious pathogen, most commonly, viral, fungal, or parasitic. The topic also includes examples of meningitis mediated by bacteria or other agents, which can produce extrameningeal symptoms such as lethargy or seizures, in which case, the combined term “meningoencephalitis” is used. There are also many examples of encephalitis not due to direct central nervous system (CNS) infections. Inflammatory processes due to an acute or chronic illness can result in an acute immune-mediated encephalitis, such as acute disseminated encephalomyelitis (ADEM), lupus cerebritis, and paraneoplastic syndromes. Agents or conditions that produce slowly progressive CNS symptoms, such as tertiary syphilis or “slow viruses” (the prion protein encephalopathies), also are considered examples of encephalitis. Table 1 lists only a limited number of the many pathogens and pathologic conditions that can cause either acute or subacute encephalitis. In this discussion, …

Pontomedullary lacerations in pedestrians: an autopsy study

It is common that injuries to the head are among the most frequent injuries found in pedestrian accidents, and can constitute a serious, if not fatal, threat. Brainstem lesions have only occasionally been reported in pedestrian injuries. The aim of this study has been to determine the frequency of brainstem pontomedullary lacerations (PMLs) among fatally injured pedestrians, the frequency of concomitant cranial, facial and cervical spine injuries in such cases, as well as to establish their possible underlying mechanism. In this work, PML was present in a significant number of fatally injured pedestrians from a sample of 50 out of 360 cases with head injuries (14%). When observed alone, the most frequent head impact areas were the chin, lateral and frontal (χ(2) = 14.200, df = 4, P = 0.007) in the subgroup with PML. Hinge fractures were most often seen in this subgroup (25 cases), followed by the absence of skull base fractures (χ(2) = 26.320, df = 3, P < 0.01). There are several possible mechanisms of PML in these cases. Impact to the chin, with or without a skull base fracture, could lead to this fatal injury due to impact force transmission. Additionally, lateral head impacts, the most frequent in pedestrians, with subsequent hinge fractures, PML and fronto-posterior hyperextension of the head that is associated with upper-spine fractures, may be possible mechanisms of brainstem injury in fatally injured pedestrians.

Focal traumatic brain stem injury is a rare type of head injury resulting from assault: A forensic neuropathological study

IntroductionBrainstem haemorrhage is common in cases of head injury when it is associated with space-occupying lesion and increases in the intracranial pressure (duret haemorrhage), in cases of diffuse axonal injury (in dorso-lateral quadrant) and diffuses vascular injury (in the periventricular tissue). However focal traumatic brainstem injury is rare. Material and methodWe identified 12 cases of focal traumatic brainstem injury from review of 319 case of head injury. The head trauma had been caused by different mechanisms of complex fall from height and assault. 10/12 are associated with skull fracture, 11/12 with contre coup contusions in the frontal and temporal lobes, 5/12 direct contusions to cerebellum, 5/12 haemorrhage in corpus callosum and 2/11 have gliding contusions. None of the cases had pathological evidence of increase in the intracranial pressure. The bleeding in the pons was at the edge in 2/12 and cross the section in 10/12. The majority of patients were unconscious immediately after the incident (10/12) and 9/12 died within one day. ConclusionFocal traumatic brainstem injury occurs most likely due to direct impact at the back of the head or stretching forces affecting the brainstem in cases of complex fall from height and after assault, particularly those associated with kicks. It is a serious and commonly fatal brain damage, which needed to be differentiated from other causes of brainstem haemorrhages.

The Prognostic Factors Related to Traumatic Brain Stem Injury

ObjectiveThis study was conducted to assess the clinical significance of traumatic brain stem injury (TBSI) reflected on Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS) by various clinical variables.MethodsA total of 136 TBSI patients were selected out of 2695 head-injured patients. All initial computerized tomography and/or magnetic resonance imaging studies were retrospectively analyzed according to demographic- and injury variables which result in GCS and GOS.ResultsIn univariate analysis, mode of injury showed a significant effect on combined injury (p<0.001), as were the cases with skull fracture on radiologic finding (p<0.000). The GCS showed a various correlation with radiologic finding (p<0.000), mode of injury (p<0.002), but less favorably with impact site (p<0.052), age (p<0.054) and skull fracture (p<0.057), in order of statistical significances. However, only GOS showed a definite correlation to radiologic finding (p<0.000). In multivariate analysis, the individual variables to enhance an unfavorable effect on GCS were radiologic finding [odds ratio (OR) 7.327, 95% confidence interval (CI)], mode of injury (OR; 4.499, 95% CI) and age (OR; 3.141, 95% CI). Those which influence an unfavorable effect on GOS were radiologic finding (OR; 25.420, 95% CI) and age (OR; 2.674, 95% CI).ConclusionIn evaluation of TBSI on outcome, the variables such as radiological finding, mode of injury, and age were revealed as three important ones to have an unfavorable effect on early stage outcome expressed as GCS. However, mode of injury was shown not to have an unfavorable effect on late stage outcome as GOS. Among all unfavorable variables, radiological finding was confirmed as the only powerful prognostic variable both on GCS and GOS.

Prognostic value of various intracranial pathologies in traumatic brain injury.

Various intracranial pathologies in traumatic brain injury (TBI) can help to predict patient outcomes. These pathologies can be categorised using the Marshall Classification or the Abbreviated Injury Scale (AIS) dictionary or can be described through traditional descriptive terms such as subarachnoid haemorrhage (SAH), subdural haemorrhage (SDH), epidural haemorrhage (EDH) etc. The purpose of this study is to assess the prognostic value of AIS scores, the Marshall Classification and various intracranial pathologies in TBI. A dataset of 802 TBI patients in the Trauma Audit and Research Network (TARN) database was analysed using logistic regression. First, a baseline model was constructed with age, Glasgow Coma Scale (GCS), pupillary reactivity, cause of injury and presence/absence of extracranial injury as predictors and survival at discharge as the outcome. Subsequently, AIS score, the Marshall Classification and various intracranial pathologies such as haemorrhage, SAH or brain swelling were added in order to assess the relative predictive strength of each variable and also to assess the improvement in the performance of the model. Various AIS scores or Marshal classes did not appear to significantly affect the outcome. Among traditional descriptive terms, only brain stem injury and brain swelling significantly influenced outcome [odds ratios for survival: 0.17 (95% confidence interval [CI]; 0.08-0.40) and 0.48 (95% CI; 0.29-0.80), respectively]. Neither haemorrhage nor its subtypes, such as SAH, SDH and EDH, were significantly associated with outcome. Adding AIS scores, the Marshall Classification and various intracranial pathologies to the prognostic models resulted in an almost equal increase in the predictive performance of the baseline model. In this relatively recent dataset, each of the brain injury classification systems enhanced equally the performance of an early mortality prediction model in traumatic brain injury patients. The significant effect of brain swelling and brain stem injury on the outcome in comparison to injuries such as SAH suggests the need to improve therapeutic approaches to patients who have sustained these injuries.

Brain-Stem Laceration and Blunt Rupture of Thoracic Aorta

Some of the fatally injured car occupants could have had both blunt rupture of thoracic aorta with great amount of intrapleural blood, and pontomedullar laceration of brain-stem as well, with both injuries being fatal. The aim of this study was to answer if all intrapleural bleeding in these cases was antemortem, or the bleeding could also be partially postmortem. We observed the group of 66 cases of blunt aortic rupture: 21 case with brain-stem laceration, and 45 cases without it. The average amount of intrapleural bleeding in cases without brain-stem laceration (1993 ± 831 mL) was significantly higher than in those with this injury (1100 ± 708 mL) (t = 4.252, df = 64, P = 0.000). According to our results, in cases of the thoracic aorta rupture with concomitant brain-stem laceration, the amount of intrapleural bleeding less than 1500 mL, should be considered mostly as postmortem in origin, and in such cases, only the brain-stem injury should be considered as cause of death.

Tectorial Membrane Injury: Frequently Overlooked in Pediatric Traumatic Head Injury

REHs and tectorial membrane injuries are rare complications of pediatric head and neck injuries. We aim to describe the neuroimaging findings in pediatric REHs, to summarize the mechanism of injury, and to correlate the imaging findings with the clinical presentation. We retrospectively evaluated CT and/or MR imaging studies of 10 children with traumatic REH. Most patients were involved in MVAs. The tectorial membrane was injured in 70% of patients, and REHs were medium to large in 80%. None of the patients had a focal spinal cord or brain stem injury, craniocervical junction dislocation, or vertebral fractures. Tectorial membrane disruption was diagnosed in most patients without craniocervical junction-related symptoms. Tectorial membrane lesions and REHs were seen in young children who sustained high-speed head and neck injuries. Clinical symptoms may be minimal or misleading. The radiologist should be aware of these injuries in children. MR imaging appears to be more sensitive than CT.

Nursing of elderly patients with severe brain injury after tracheotomy

Objective To discuss and summarize nursing measures of elderly patients with severe brain injury after tracheotomy. Methods A retrospective analysis was carried out in 60 elderly patients with severe traumatic brain injury after tracheotomy in our hospital from July, 2009 to August, 2010, all patients were given holistic nursing care, including close observation of patients' condition, controlling the suction time, methods and techniques, strict aseptic technique, to effectively prevent infection. Results In the implementation of the patient-centered holistic care, the results were significant, 49 cases survived the acute phase and finally removed tracheal tube. Only 5 patients had pulmonary infection, accounting for 8.3%. 3 patients died due to brain injury and 5 cases were discharged against advice, 3 patients did not gain extubation due to severe brain stem injury. Conclusions The patients with severe head injury need tracheotomy to maintain airway patency, timely call-back, suction, effective airway humidification, prevention of pulmonary infection, reduction of respiratory tract injury is key to successful treatment. The patientcentered holistic care is worthy of wide clinical application. Key words: Severe brain injury; Tracheotomy; Care

Predicting motor outcome and death in term hypoxic-ischemic encephalopathy

Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions. From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System. The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death. We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.

SU‐D‐BRC‐05: Characterizing Therapy‐Induced Brainstem Injury and Recovery with Serial Diffusion Tensor Imaging

Purpose: To characterize therapy‐induced changes in normal‐appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods: We analyzed sequential DTI of 20 brain tumor patients, aged 4–23 years, with normal‐appearing brainstems included in the radiation treatment fields. Prescribed tumor doses ranged from 54 to 59.4 Gy. Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and registered to three‐dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age‐related benchmark for comparison, DTI studies from 20 healthy volunteers, aged 6–25 years, were included in the analysis. Results: The median DTI follow‐up was 3.5 years (range, 1.6–5.0 years). The median mean dose to the pons was 56 Gy (range, 7–59 Gy). Three distinctive patterns of temporal changes in FA and ADC were observed in the pons: (1) a stable or normal developing time trend similar to those observed in healthy children, (2) initial deviation from normal with subsequent recovery, (3) progressive deviation without evidence of complete recovery. In this group of patients without severe brainstem necrosis, maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long‐term recovery patterns. Conclusions: Longitudinal DTI analysis revealed variation among individual patients in diffusion properties of brainstems reflecting therapy‐induced white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years following radiation therapy. Attention should be given to patients with pronounced early changes since DTI suggested their recovery was slower and less complete than other patients.Acknowledgement: NIH grant HD049888.

Prognostic Value of Magnetic Resonance Imaging in Moderate and Severe Head Injury: A Prospective Study of Early MRI Findings and One-Year Outcome

The clinical benefit of early magnetic resonance imaging (MRI) in severe and moderate head injury is unclear. We sought to explore the prognostic value of the depth of lesions depicted with early MRI, and also to describe the prevalence and impact of traumatic brainstem lesions. In a cohort of 159 consecutive patients with moderate to severe head injury (age 5-65 years and surviving the acute phase) admitted to a regional level 1 trauma center, 106 (67%) were examined with MRI within 4 weeks post-injury. Depth of lesions in MRI was categorized as: hemisphere level, central level, and brainstem injury (BSI). The outcome measure was Glasgow Outcome Scale Extended (GOSE) 12 months post-injury. Forty-six percent of patients with severe injuries and 14% of patients with moderate injuries had BSI. In severe head injury, central or brainstem lesions in MRI, together with higher Rotterdam CT score, pupillary dilation, and secondary adverse events were significantly associated with a worse outcome in age-adjusted analyses. Bilateral BSI was strongly associated with a poor outcome in severe injury, with positive and negative predictive values of 0.86 and 0.88, respectively. In moderate injury, only age was significantly associated with outcome in multivariable analyses. Limitations of the current study include lack of blinded outcome evaluations and insufficient statistical power to assess the added prognostic value of MRI when combined with clinical information. We conclude that in patients with severe head injury surviving the acute phase, depth of lesion on the MRI was associated with outcome, and in particular, bilateral brainstem injury was strongly associated with poor outcomes. In moderate head injury, surprisingly, there was no association between MRI findings and outcome when using the GOSE score as outcome measure.

Feasibility of Proton Beam Therapy for Chordoma and Chondrosarcoma of the Skull Base

We explored the general feasibility of proton beam therapy for chordoma and chondrosarcoma of the skull base. Clinical records and treatment-planning data of patients with the pathological diagnosis of chordoma or chondrosarcoma were examined. Proton beam therapy was administered for gross tumor mass as well as microscopic residual disease after surgery. The prescribed dose was determined to maximize the coverage of the target and to not exceed predefined constraints for the organs at risk. Eight cases of chordoma and eight cases of chondrosarcoma were enrolled. The median tumor volume was 40 cm(3) (range, 7 to 546 cm(3)). The prescribed dose ranged from 50 to 70 Gy (relative biological effectiveness [RBE]), with a median of 63 Gy RBE. The median follow-up duration was 42 months (range 9 to 80 months). The overall survival rate was 100%, and the local control rate at 3 years of chordoma and chondrosarcoma were 100% and 86%. None of the patients developed radiation-induced optic neuropathy, brain stem injury, or other severe toxicity. Proton beam therapy is generally feasible for both chordoma and chondrosarcoma of the skull base, with excellent local control and survival rates.