Multicenter study of 37 pediatric patients with SCIWORA or other spinal cord injury without associated bone lesion.

BACKGROUND: Pure traumatic spinal cord injury (without associated bone lesion) are encountered in pediatric accidentology, the most typical being spinal cord injury without radiological abnormality (SCIWORA). The present study reports a multicenter series of under-18-year-olds admitted for traumatic medullary lesion. The objectives were: (1) to describe the causes of pure spinal cord injuries in children in France and their clinical presentation; (2) to identify any prognostic factors; and (3) to describe their medical management in France. PATIENTS AND METHOD: A multicenter retrospective study was conducted in 3 pediatric spine pathology reference centers. Files of 37 patients with confirmed spinal cord injury between January 1988 and June 2017 were analyzed: SCIWORA (n=30), myelopathy associated with severe cranial trauma (n=2), and obstetric trauma (n=5). Accident causes, associated lesions, initial Frankel grade, level of clinical spinal cord injury, initial MRI findings, type of treatment and neurology results at last follow-up were collated. The main endpoint was neurologic recovery, defined by improvement of at least 1 Frankel grade. RESULTS: Causes comprised 17 road accidents, 11 sports accidents, 5 obstetric lesions and 4 falls. Mean follow-up was 502 days. The rate of at least partial neurologic recovery was 20/30 in SCIWORA, 0/5 in obstetric trauma, and 0/4 in case of associated intracranial lesion. In SCIWORA, factors associated with recovery comprised age, accident type, and absence of initial MRI lesion. DISCUSSION: We report a large series of pediatric spinal cord injury without associated bone lesion. This is a potentially serious pathology, in which prognosis is mainly related to age and trauma mechanism. LEVEL OF EVIDENCE: IV, case series.

Decompressive Craniectomy in Children with Severe Traumatic Brain Injury: A Multicenter Retrospective Study and Literature Review.

BACKGROUND: Severe traumatic brain injury (TBI) is the most common cause of disability in children. Refractory increased intracranial pressure can be a therapeutic challenge. Decompressive craniectomy can be proposed when medical management is insufficient, but its place is not clearly defined in guidelines. The aim of this study was to identify prognostic factors in children with TBI. METHODS: We performed a retrospective, multicenter study to analyze long-term outcomes of 150 children with severe TBI treated by decompressive craniectomy and to identify prognostic factors. RESULTS: A satisfactory neurologic evolution (represented by a King's Outcome Scale for Childhood Head Injury score >3) was observed in 62% of children with a mean follow-up of 3.5 years. Mortality rate was 17%. Prognostic factors associated with outcome were age, initial Glasgow Coma Scale score, presence of mydriasis, neuromonitoring values (maximal intracranial pressure >30 mm Hg), and radiologic findings (Rotterdam score ≥4). CONCLUSIONS: This study in a large population confirms that children with severe TBI treated by decompressive craniectomy can achieve a good neurologic outcome. Further studies are needed to clarify the use of this surgery in the management of children with severe TBI.

Regenerative potential of primary adult human neural stem cells on micropatterned bio-implants boosts motor recovery.

BACKGROUND: The adult brain is unable to regenerate itself sufficiently after large injuries. Therefore, hopes rely on therapies using neural stem cell or biomaterial transplantation to sustain brain reconstruction. The aim of the present study was to evaluate the improvement in sensorimotor recovery brought about by human primary adult neural stem cells (hNSCs) in combination with bio-implants. METHODS: hNSCs were pre-seeded on implants micropatterned for neurite guidance and inserted intracerebrally 2 weeks after a primary motor cortex lesion in rats. Long-term behaviour was significantly improved after hNSC implants versus cell engraftment in the grip strength test. MRI and immunohistological studies were conducted to elucidate the underlying mechanisms of neuro-implant integration. RESULTS: hNSC implants promoted tissue reconstruction and limited hemispheric atrophy and glial scar expansion. After 3 months, grafted hNSCs were detected on implants and expressed mature neuronal markers (NeuN, MAP2, SMI312). They also migrated over a short distance to the reconstructed tissues and to the peri-lesional tissues, where 26% integrated as mature neurons. Newly formed host neural progenitors (nestin, DCX) colonized the implants, notably in the presence of hNSCs, and participated in tissue reconstruction. The microstructured bio-implants sustained the guided maturation of both grafted hNSCs and endogenous progenitors. CONCLUSIONS: These immunohistological results are coherent with and could explain the late improvement observed in sensorimotor recovery. These findings provide novel insights into the regenerative potential of primary adult hNSCs combined with microstructured implants.

Response Assessment in Neuro-Oncology criteria, contrast enhancement and perfusion MRI for assessing progression in glioblastoma.

PURPOSE: The purpose of the study was to evaluate Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma multiforme (GBM), with respect to the Macdonald criteria and changes in contrast-enhancement (CE) volume. Related variations in relative cerebral blood volume (rCBV) were investigated. METHODS: Forty-three patients diagnosed between 2006 and 2010 were included. All underwent surgical resection, followed by temozolomide-based chemoradiation. MR images were retrospectively reviewed. Times to progression (TTPs) according to RANO criteria, Macdonald criteria and increased CE volume (CE-3D) were compared, and the percentage change in the 75th percentile of rCBV (rCBV75) was evaluated. RESULTS: After a median follow-up of 22.7 months, a total of 39 patients had progressed according to RANO criteria, 32 according to CE-3D, and 42 according to Macdonald. Median TTPs were 6.4, 9.3, and 6.6 months, respectively. Overall agreement was 79.07% between RANO and CE-3D and 93.02% between RANO and Macdonald. The mean percentage change in rCBV75 at RANO progression onset was over 73% in 87.5% of patients. CONCLUSIONS: In conclusion, our findings suggest that CE-3D criterion is not yet suitable to assess progression in routine clinical practice. Indeed, the accurate threshold is still not well defined. To date, in our opinion, early detection of disease progression by RANO combined with advanced MRI imaging techniques like MRI perfusion and diffusion remains the best way to assess disease progression. Further investigations that would examine the impact of treatment modifications after progression determined by different criteria on overall survival would be of great value.

Corticospinal Tract Tracing in the Marmoset with a Clinical Whole-Body 3T Scanner Using Manganese-Enhanced MRI.

Manganese-enhanced MRI (MEMRI) has been described as a powerful tool to depict the architecture of neuronal circuits. In this study we investigated the potential use of in vivo MRI detection of manganese for tracing neuronal projections from the primary motor cortex (M1) in healthy marmosets (Callithrix Jacchus). We determined the optimal dose of manganese chloride (MnCl2) among 800, 400, 40 and 8 nmol that led to manganese-induced hyperintensity furthest from the injection site, as specific to the corticospinal tract as possible, and that would not induce motor deficit. A commonly available 3T human clinical MRI scanner and human knee coil were used to follow hyperintensity in the corticospinal tract 24h after injection. A statistical parametric map of seven marmosets injected with the chosen dose, 8 nmol, showed the corticospinal tract and M1 connectivity with the basal ganglia, substantia nigra and thalamus. Safety was determined for the lowest dose that did not induce dexterity and grip strength deficit, and no behavioral effects could be seen in marmosets who received multiple injections of manganese one month apart. In conclusion, our study shows for the first time in marmosets, a reliable and reproducible way to perform longitudinal ME-MRI experiments to observe the integrity of the marmoset corticospinal tract on a clinical 3T MRI scanner.

Is there any benefit from short-term perioperative antiepileptic prophylaxis in patients with chronic subdural haematoma? A retrospective controlled study.

BACKGROUND: Chronic subdural haematoma is a common pathology, which can be complicated by seizures. Seizures may worsen the outcome of patients presenting with a chronic subdural haematoma. However, since the overall and postoperative incidence of seizures and their impact on patients' outcome has been diversely appreciated in the literature, the interest of routine antiepileptic prophylaxis remains a controversial question. METHODS: We retrospectively investigated 99 patients who were surgically treated for a chronic subdural haematoma in two French academic hospitals: 48 patients received antiepileptic prophylaxis (group A) and were compared with a group of 51 patients who did not receive any antiepileptic prophylaxis (group B). Incidence of perioperative seizures was determined, and potential risk factors for epilepsy were analysed. RESULTS: Overall postoperative seizure incidence was 5.1%. There was a slight trend towards a lower incidence of seizures in patients who had received antiepileptic prophylaxis, but no significant difference was found between the two groups (4.2% in group A versus 5.9% in group B, P=0.697). Seizures were not correlated with increased death. No risk factor for seizures was identified. CONCLUSIONS: Our retrospective data showed there is no benefit of perioperative antiepileptic prophylaxis in patients surgically treated for chronic subdural haematoma. Since other authors have shown conflicting results, sufficiently powered prospective randomized study should be conducted in order to confirm these results.

Strength and fine dexterity recovery profiles after a primary motor cortex insult and effect of a neuronal cell graft.

The aim of this study was to set up (a) a large primary motor cortex (M1) lesion in rodent and (b) the conditions for evaluating a long-lasting motor deficit in order to propose a valid model to test neuronal replacement therapies aimed at improving motor deficit recovery. A mitochondrial toxin, malonate, was injected to induce extensive destruction of the forelimb M1 cortex. Three key motor functions that are usually evaluated following cerebral lesion in the clinic-strength, target reaching, and fine dexterity-were assessed in rats by 2 tests, a forelimb grip strength test and a skilled reaching task (staircase) for reaching and dexterity. The potential enhancement of postlesion recovery induced by a neuronal cell transplantation was then explored and confirmed by histological analyses. Both tests showed a severe functional impairment 2 days post lesion, however, reaching remained intact. Deficits in forelimb strength were long lasting (up to 3 months) but spontaneously recovered despite the extensive lesion size. This natural grip strength recovery could be enhanced by cell therapy. Histological analyses confirmed the presence of grafted cells 3 months postgraft and showed partial tissue reconstruction with some living neuronal cells in the graft. In contrast, fine dexterity never recovered in the staircase test even after grafting. These results suggest that cell replacement was only partially effective and that the forelimb M1 area may be a node of the sensorimotor network, where compensation from secondary pathways could account for strength recovery but recovery of forelimb fine dexterity requires extensive tissue reconstruction.