North American survey on the post-neuroimaging management of children with mild head injuries.

OBJECTIVEThere remains uncertainty regarding the appropriate level of care and need for repeating neuroimaging among children with mild traumatic brain injury (mTBI) complicated by intracranial injury (ICI). This study's objective was to investigate physician practice patterns and decision-making processes for these patients in order to identify knowledge gaps and highlight avenues for future investigation.METHODSThe authors surveyed residents, fellows, and attending physicians from the following pediatric specialties: emergency medicine; general surgery; neurosurgery; and critical care. Participants came from 10 institutions in the United States and an email list maintained by the Canadian Neurosurgical Society. The survey asked respondents to indicate management preferences for and experiences with children with mTBI complicated by ICI, focusing on an exemplar clinical vignette of a 7-year-old girl with a Glasgow Coma Scale score of 15 and a 5-mm subdural hematoma without midline shift after a fall down stairs.RESULTSThe response rate was 52% (n = 536). Overall, 326 (61%) respondents indicated they would recommend ICU admission for the child in the vignette. However, only 62 (12%) agreed/strongly agreed that this child was at high risk of neurological decline. Half of respondents (45%; n = 243) indicated they would order a planned follow-up CT (29%; n = 155) or MRI scan (19%; n = 102), though only 64 (12%) agreed/strongly agreed that repeat neuroimaging would influence their management. Common factors that increased the likelihood of ICU admission included presence of a focal neurological deficit (95%; n = 508 endorsed), midline shift (90%; n = 480) or an epidural hematoma (88%; n = 471). However, 42% (n = 225) indicated they would admit all children with mTBI and ICI to the ICU. Notably, 27% (n = 143) of respondents indicated they had seen one or more children with mTBI and intracranial hemorrhage demonstrate a rapid neurological decline when admitted to a general ward in the last year, and 13% (n = 71) had witnessed this outcome at least twice in the past year.CONCLUSIONSMany physicians endorse ICU admission and repeat neuroimaging for pediatric mTBI with ICI, despite uncertainty regarding the clinical utility of those decisions. These results, combined with evidence that existing practice may provide insufficient monitoring to some high-risk children, emphasize the need for validated decision tools to aid the management of these patients.

The Economic and Clinical Impact of Sustained Use of a Progressive Mobility Program in a Neuro-ICU.

OBJECTIVE: To investigate a progressive mobility program in a neurocritical care population with the hypothesis that the benefits and outcomes of the program (e.g., decreased length of stay) would have a significant positive economic impact. DESIGN: Retrospective analysis of economic and clinical outcome data before, immediately following, and 2 years after implementation of the Progressive Upright Mobility Protocol Plus program (UF Health Shands Hospital, Gainesville, FL) involving a series of planned movements in a sequential manner with an additional six levels of rehabilitation in the neuro-ICU at UF Health Shands Hospital. SETTING: Thirty-bed neuro-ICU in an academic medical center. PATIENTS: Adult neurologic and neurosurgical patients: 1,118 patients in the pre period, 731 patients in the post period, and 796 patients in the sustained period. INTERVENTIONS: Implementation of Progressive Upright Mobility Protocol Plus. MEASUREMENTS AND MAIN RESULTS: ICU length of stay decreased from 6.5 to 5.8 days in the immediate post period and 5.9 days in the sustained period (F(2,2641) = 3.1; p = 0.045). Hospital length of stay was reduced from 11.3 ± 14.1 days to 8.6 ± 8.8 post days and 8.8 ± 9.3 days sustained (F(2,2641) = 13.0; p < 0.001). The impact of the study intervention on ICU length of stay (p = 0.031) and hospital length of stay (p < 0.001) remained after adjustment for age, sex, diagnoses, sedation, and ventilation. Hospital-acquired infections were reduced by 50%. Average total cost per patient after adjusting for inflation was significantly reduced by 16% (post period) and 11% (sustained period) when compared with preintervention (F(2,2641) = 3.1; p = 0.045). Overall, these differences translated to an approximately $12.0 million reduction in direct costs from February 2011 through the end of 2013. CONCLUSIONS: An ongoing progressive mobility program in the neurocritical care population has clinical and financial benefits associated with its implementation and should be considered.

Fighting fire with fire: the revival of thermotherapy for gliomas.

In 1891, an orthopedic surgeon in New York noted the disappearance of an inoperable sarcoma in a patient after a febrile illness. This observation resulted in experiments assessing the utility of heat therapy or thermotherapy for the treatment of cancer. While it initially fell from favor, thermotherapy has recently made a resurgence, sparking investigations into its anticancer properties. This therapy is especially attractive for glioblastoma multiforme (GBM) which is difficult to target due to the blood-brain barrier and recalcitrant to treatment. Here we briefly review the history of thermotherapy and then more methodically present the current literature as it relates to central nervous system malignancies. Recent developments show that heat is preferentially cytotoxic to tumor cells and induces cellular pathways which result in apoptotic and non-apoptotic death. Techniques to induce hyperthermia include regional hyperthermia by water bath, focused ultrasound, radiofrequency microwaves, laser-induced interstitial thermotherapy, and magnetic energy. The recent revival of these therapeutic approaches and their preliminary outcomes in the treatment of GBM is reviewed. From bacterial toxins to infusion of magnetic nanoparticles, hyperthermia has the potential to be an effective and easy-to-execute adjuvant therapy for GBM. Hyperthermia for GBM is a promising therapy as part of a growing armamentarium for malignant glioma treatment.

Characterizing phospholipase A2-induced spinal cord injury-a comparison with contusive spinal cord injury in adult rats.

To assess whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI), we compared lesions either induced by PLA2 alone or by a contusive SCI. At 24-h post-injury, both methods induced a focal hemorrhagic pathology. The PLA2 injury was mainly confined within the ventrolateral white matter, whereas the contusion injury widely affected both the gray and white matter. A prominent difference between the two models was that PLA2 induced a massive demyelination with axons remaining in the lesion area, whereas the contusion injury induced axonal damage and myelin breakdown. At 4 weeks, no cavitation was found within the PLA2 lesion, and numerous axons were myelinated by host-migrated Schwann cells. Among them, 45% of animals had early transcranial magnetic motor-evoked potential (tcMMEP) responses. In contrast, the contusive SCI induced a typical centralized cavity with reactive astrocytes forming a glial border. Only 15% of rats had early tcMMEP responses after the contusion. BBB scores were similarly reduced in both models. Our study indicates that PLA2 may play a unique role in mediating secondary SCI likely by targeting glial cells, particularly those of oligodendrocytes. This lesion model could also be used for studying demyelination and remyelination in the injured spinal cord associated with PLA2-mediated secondary SCI.

A novel role of phospholipase A2 in mediating spinal cord secondary injury.

OBJECTIVE: To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI). METHODS: Biochemical, Western blot, histological, immunohistochemical, electron microscopic, electrophysiological, and behavior assessments were performed to investigate (1) SCI-induced PLA2 activity, expression, and cellular localization after a contusive SCI; and (2) the effects of exogenous PLA2 on spinal cord neuronal death in vitro and tissue damage, inflammation, and function in vivo. RESULTS: After SCI, both PLA2 activity and cytosolic PLA2 expression increased significantly, with cytosolic PLA2 expression being localized mainly in neurons and oligodendrocytes. Both PLA2 and melittin, an activator of endogenous PLA2, induced spinal neuronal death in vitro, which was substantially reversed by mepacrine, a PLA2 inhibitor. When PLA2 or melittin was microinjected into the normal spinal cord, the former induced confined demyelination and latter diffuse tissue necrosis. Both injections induced inflammation, oxidation, and tissue damage, resulting in corresponding electrophysiological and behavioral impairments. Importantly, the PLA2-induced demyelination was significantly reversed by mepacrine. INTERPRETATION: PLA2, increased significantly after SCI, may play a key role in mediating neuronal death and oligodendrocyte demyelination following SCI. Blocking PLA2 action may represent a novel repair strategy to reduce tissue damage and increase function after SCI.