Myelomeningocele repair

The closure of the skin defect in myelomeningocele (MMC) repair is an essential step that determines the quality of the surgical result. The success of surgical results is related to the decision to use the most suitable techniques, namely flaps or primary closure.

In cases of myelomeningocele, some prefer to place the shunt and close the defect in the same procedure, it reduces the risks inherent to exposure to anesthesia, reduces hospital stay, and related costs. If there is a suspicious of infection, they do not place the shunt on the same procedure 1).

Prenatal therapeutic strategies that interrupt progressive pathological processes offer an appealing approach for treatment of MMC. However, a thorough understanding of pathological progression of MMC is mandatory for appropriate treatment to be rendered 2).

Closure of the defect.

MOMS Trial

see MOMS Trial.

Case series

A prospective study of Zarutskie et al., from the Baylor College of MedicineTexas Children’s HospitalLucile Packard Children’s Hospital Stanfordfrom fetuses diagnosed with open neural tube defect that had in-utero myelomeningocele repair between April 2014 and April 2016. Independent variables were collected from four chronological sets of fetal images: pre-surgery ultrasound, pre-surgery MRI, 6-week post-surgery MRI and pre-delivery ultrasound. The following independent variables were collected from all image sets unless otherwise noted: gestational age, head circumference, mean ventricular width, ventricular volume (VV, MRI only), hindbrain herniation (HBH) score (MRI only), and level of lesion, defined as the upper bony spinal defect (pre-surgery US). Based on these measurements, additional variables were defined and calculated including change in degree of HBH, ventricular width growth (mm/week), and ventricular volume growth (ml/week). The need for hydrocephalus HT (by either ventriculoperitoneal shunt or endoscopic third ventriculostomy and choroid plexus cauterization (ETV-CPC)) was determined by a pediatric neurosurgeon using clinical and radiographic criteria; a secondary analysis was performed using the MOMS trial criteria for hydrocephalus. The predictive value of each parameter was assessed by ROC-curve and logistic regression analyses.

Fifty affected fetuses were included in the study, of which 32 underwent open hysterotomy and 18 fetoscopic repair. Two cases of neonatal death were excluded from the analysis. The mean gestational ages for the pre-surgery ultrasound, pre-surgery MRI, post-surgery MRI and pre-delivery ultrasound were 21.8 ± 2.1 weeks, 22.0 ±1.8 weeks, 30.4 ±1.6 weeks and 31.0 ±4.9 weeks, respectively. A total of 16 subjects required HT. Area under the curve (AUC) of predictive accuracy for HT showed that HBH grading on post-surgery MRI had the strongest predictive value (0.86; p<0.01), outperforming other predictors such as mean ventricular width on pre-surgery US (0.67; p=0.05), post-surgery MRI VV (0.73; p=0.03), MRI VV growth (0.79; p=0.01), change in HBH (0.82; p<0.01), and mean ventricular width on pre-delivery US (0.73; p=0.01). Other variables such as mean ventricular width on pre-surgery and post-surgery MRI, and ventricular growth assessment by MRI or US, had an AUC<0.7. Optimal cut-offs of the variables with the highest AUCs were evaluated to improve prediction. A combination of ventricular volume growth ≥ 2.02 ml/week and/or HBH of 3 on post-surgery MRI were the optimal cut-offs for the best prediction [OR: 42 (95% CI: 4 – 431), accuracy: 84%]. Logistic regression analyses also showed that persistence of severe HBH 6 weeks after surgery by MRI is one of the best predictors for HT [OR 39 (95% CI: 4 – 369), accuracy: 84%]. There was no significant change in the results when the MOMS trial criteria for hydrocephalus were used as the dependent variable 3).


Sanz-Cortés et al., described and compared placental and amniotic histology in women who underwent a fetoscopic myelomeningocele repair to those who underwent an open-hysterotomy myelomeningocele repair. Also, we intended to compare findings from both prenatal repair groups to age-matched control pregnant patients.

Placental and membrane histopathology from 43 prenatally repaired spina bifida cases (17 fetoscopic and 26 open) and 18 healthy controls were retrospectively assessed. Quantitative assessment of histopathology included apoptosis count, maternal and fetal underperfusion scores. Qualitative assessment included the detection of pigmented macrophages and/or signs of placental/amniotic inflammation. Associations between the duration of surgery or the duration of CO2 insufflation and quantitative histological parameters were tested.

Fetoscopic surgery cases did not show significant differences in any of the studied parameters when compared against controls. No differences were detected either when compared to open-repaired cases, except for lower proportion of pigmented laden macrophages in the fetoscopic group (11.8% vs 61.5% p<0.01). No associations between the duration of surgery or the duration of CO2 exposure and any of the quantitative histological parameters were detected.

These preliminary results support the lack of detrimental effects of the use of heated and humidified CO2 gas for uterine insufflation to fetal membranes and placenta 4).

References

1)

Bao N, Lazareff J. How I Do It: Management of spina bifida in a hospital in The People’s Republic of China. Surg Neurol Int. 2015 Jul 23;6(Suppl 11):S337-45. doi: 10.4103/2152-7806.161410. eCollection 2015. PubMed PMID: 26236554; PubMed Central PMCID: PMC4521313.
2)

Smith GM, Krynska B. Myelomeningocele: How we can improve the assessment of the most severe form of spina bifida. Brain Res. 2014 Dec 9. pii: S0006-8993(14)01659-X. doi: 10.1016/j.brainres.2014.11.053. [Epub ahead of print] PubMed PMID: 25498106.
3)

Zarutskie A, Guimaraes C, Yepez M, Torres P, Shetty A, Sangi-Haghpeykar H, Lee W, Espinoza J, Shamshirsaz A, Nassr A, Belfort M, Whitehead W, Sanz Cortes M. Prenatal brain imaging for predicting postnatal hydrocephalus treatment in fetuses that had neural tube defect repair. Ultrasound Obstet Gynecol. 2019 Jan 8. doi: 10.1002/uog.20212. [Epub ahead of print] PubMed PMID: 30620440.
4)

Sanz-Cortés M, Castro E, Sharhan D, Torres P, Yepez M, Espinoza J, Shamshirsaz AA, Nassr AA, Popek E, Whitehead W, Belfort MA. AMNIOTIC MEMBRANE AND PLACENTAL HISTOPATHOLOGICAL FINDINGS AFTER OPEN AND FETOSCOPIC PRENATAL NEURAL TUBE DEFECT REPAIR. Prenat Diagn. 2019 Jan 4. doi: 10.1002/pd.5414. [Epub ahead of print] PubMed PMID: 30609053.

Pediatric glioblastoma

Glioblastoma in children, when compared with adults, is relatively rare.

Despite this rarity, it is apparent from the limited number of publications that pediatric glioblastoma is quite distinct from their adult counterparts. The differences pertain to the molecular genetics, effectiveness of the adjuvant therapies, and possibly the prognosis after treatment. With a plethora of path-breaking translational research coming through in recent times, a host of new information is now available on pediatric glioblastomas that holds great promise as far as the future treatment options are concerned 1)

In contrast to adult GBM, few molecular prognostic markers for the pediatric counterpart have been established.


Some anaplastic pleomorphic xanthoastrocytomas (PXA) were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome-wide molecular analysis, Nakamura et al., showed an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA 2).


Korshunov et al. investigated the prognostic significance of genomic and epigenetic alterations through molecular analysis of 202 pedGBM (1-18 years) with comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin-embedded tumor samples were assessed for genome-wide DNA methylation profiles, with known candidate genes screened for alterations via direct sequencing or FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %) displayed methylation profiles similar to those of either low-grade gliomas or pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %), H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36 %). These subgroups were associated with specific cytogenetic aberrations, MGMT methylation patterns and clinical outcomes. Analysis of follow-up data identified a set of biomarkers feasible for use in risk stratification: pedGBM with any oncogene amplification and/or K27M mutation (n = 124) represents a particularly unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors without these markers (n = 38) define a more favorable group (3-year OS ~70 %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had distinct molecular features associated with a more favorable outcome. This refined prognostication method for pedGBM using a molecular risk algorithm may allow for improved therapeutic choices and better planning of clinical trial stratification for this otherwise devastating disease 3)

Treatment

Total resection and receiving chemotherapy adjuvant to radiation or chemoradiation (CRT) are most closely associated with improved progression free survival (PFS) and overall survival (OS). For higher risk incompletely resected patients, temozolomide use and treatment intensification with concurrent CRT, adjuvant chemotherapy, and higher radiation dose were associated with improved outcomes 4).

Bevacizumab and irinotecan are a promising regimen for pediatric cases of recurrent glioblastoma after gross-total resection, although the optimal treatment schedule must be determined on a patient-by-patient basis 5).

Case reports

A rare case of primary pediatric glioblastoma multiforme in a 7-year-old girl with Turner’s syndrome is reported, and various aspects regarding clinical and pathophysiological issues have been discussed. Although Turner’s syndrome is not one of the congenital chromosomal abnormalities which demand routine CNS screening, neurological assessment may be of value in those with relevant clinical findings 6).

1)

Das KK, Kumar R. Pediatric Glioblastoma. In: De Vleeschouwer S, editor. Glioblastoma [Internet]. Brisbane (AU): Codon Publications; 2017 Sep 27. Chapter 15. Available from http://www.ncbi.nlm.nih.gov/books/NBK469983/ PubMed PMID: 29251872.
2)

Nakamura T, Fukuoka K, Nakano Y, Yamasaki K, Matsushita Y, Yamashita S, Ikeda J, Udaka N, Tanoshima R, Shiba N, Tateishi K, Yamanaka S, Yamamoto T, Hirato J, Ichimura K. Genome-wide DNA methylation profiling shows molecular heterogeneity of anaplastic pleomorphic xanthoastrocytoma. Cancer Sci. 2019 Jan 4. doi: 10.1111/cas.13903. [Epub ahead of print] PubMed PMID: 30609203.
3)

Korshunov A, Ryzhova M, Hovestadt V, Bender S, Sturm D, Capper D, Meyer J, Schrimpf D, Kool M, Northcott PA, Zheludkova O, Milde T, Witt O, Kulozik AE, Reifenberger G, Jabado N, Perry A, Lichter P, von Deimling A, Pfister SM, Jones DT. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol. 2015 Mar 10. [Epub ahead of print] PubMed PMID: 25752754.
4)

Walston S, Hamstra DA, Oh K, Woods G, Guiou M, Olshefski RS, Chakravarti A, Williams TM. A multi-institutional experience in pediatric high-grade glioma. Front Oncol. 2015 Feb 18;5:28. doi: 10.3389/fonc.2015.00028. eCollection 2015. PubMed PMID: 25741472; PubMed Central PMCID: PMC4332307.
5)

Umeda K, Shibata H, Saida S, Hiramatsu H, Arakawa Y, Mizowaki T, Nishiuchi R, Adachi S, Heike T, Watanabe K. Long-term efficacy of bevacizumab and irinotecan in recurrent pediatric glioblastoma. Pediatr Int. 2015 Feb;57(1):169-71. doi: 10.1111/ped.12414. PubMed PMID: 25711258.
6)

Hanaei S, Habibi Z, Nejat F, Sayarifard F, Vasei M. Pediatric Glioblastoma Multiforme in Association with Turner’s Syndrome: A Case Report. Pediatr Neurosurg. 2015 Feb 25. [Epub ahead of print] PubMed PMID: 25720952.

Intracranial arachnoid cyst surgery

Controversy still exists regarding the optimal option for the surgical management of intracranial arachnoid cysts.

Options

Neuroendoscopic fenestrations.

Microsurgical fenestrations +/- marsupialisation

Cystoperitoneal shunt.

In a retrospective case note review of all patients with intracranial arachnoid cysts treated surgically at the Department of Neurosurgery, Wessex Neurological Centre, Southampton General Hospital, over a 15 year period. Data on clinical presentations and outcomes was collected from the patient notes and the pre- and post-operative cyst volumes were calculated by creating 3-dimensional volumetric models.

Eighty-two patients were identified of which 45 were treated endoscopically, 34 microscopically and 3 underwent cysto-peritoneal shunting. The most common cyst location was the middle fossa (n = 25). Amongst the symptomatic patients, improvement or resolution of symptoms was seen in 35 out of 40 cysts treated endoscopically (88%), 28 out of 32 treated microsurgically (88%) and 3 out of 3 treated by shunting (100%, p = 0.79). The reoperation rate was not significantly different between the endoscopic and microsurgical groups (24.4% vs 14.7%, p = 0.49). The endoscopic and shunted groups had a shorter length of stay than the microsurgical group (3.0 vs 3.0 vs 4.5 days, p = 0.04). All three treatment modalities had a similar percentage reduction in cyst volume after surgery (30.0 vs 41.7 vs 30.9%, p = 0.98).

This cohort series shows that endoscopic and microsurgical approaches to treat intracranial arachnoid cysts produce comparable clinical and radiological outcomes. Endoscopic fenestration is associated with a shorter length of stay as would be expected from a minimally invasive procedure 1).


Open surgery advantages include, direct inspection of the cyst, biopsy sampling, fenestration in multilocular cysts and, in certain locations, cyst communication to basal cisterns 2).

Surgery for AC can be performed with a fairly low risk of complications and yields significant improvement in quality of life correlated to postoperative improvement in headache and dizziness. These findings may justify a more liberal approach to surgical treatment for AC 3).


Choi et al., analyzed pediatric patients under 18 years of age who underwent surgical management for intracranial AC between January 2000 and December 2011. Patients with a follow-up period of less than 1 year were excluded. A total of 75 patients were enrolled in this study. These patients were assessed by subjective symptoms and by a clinician’s objective evaluation. The radiological assessment of AC after surgery was also evaluated.

The median age of patients at the initial operation was 5 years. The median follow-up period was 38 months. The goal of surgery was achieved in 28% (21/75) of patients. The radiological alteration of AC after initial fenestration surgery was diverse. The results of the clinical and radiological assessments did not always coincide. A total of 35 complications occurred in 28 patients. Subdural fluid collection was the most common unexpected radiological complication.

The study showed that the fenestration procedure for AC produced unsatisfactory clinical improvements compared to the relatively high complication rate. Therefore, surgical treatment for AC should be strictly limited to patients who have symptoms directly related to AC 4).


A consecutive series of 68 adult patients (43 males, mean age 30.3 years, range 18-42 years) with IAC were surgically treated between January 2004 and January 2011 in the Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.

The cysts were supratentorial in location in 53 and infratentorial in 15 patients. Symptoms at presentation, location of the IAC, surgical treatment modalities, and postoperative complications were evaluated.

Of the 51 patients with headache, 44 (86.27%) patients had complete relief of the headache, five (9.80%) patients had significant improvement, and two (3.92%) had no worthwhile change. Three of the four patients with hydrocephalus and gait disturbances had relief of the symptoms and one patient had significant improvement. Of the five patients with cognitive decline and weakness, three (60.00%) patients showed improvement, and two (40.00%) patients had no significant change. Five (62.50%) of the eight patients with epilepsy had seizure remission, two (25.00%) patients had non-disabling seizures, and one had no change. Follow-up computed tomography (CT) scans showed variable change in the mass effect of IAC in 68 patients; cystic size was significantly reduced in 51 patients, no significant change in two patients of supratentorial arachnoid cysts. Cystic size was reduced in seven patients, but no significant change was observed in eight patients of infratentorial cysts. Three patients with enlarged head circumference had no further increase in the head circumference.

Adult patients with IAC symptoms should be treated efficiently. Surgical treatment is associated with significant improvement in the symptoms and signs 5).


Data from 69 patients with cerebral arachnoid cysts treated in our institution between 1997 and 2007 were reviewed.Cysts were located infratentorially in 20% (n = 14) and supratentorially in 80% (n = 55); of these 73% (n = 40) were in the middle cranial fossa. Mean cyst size was 61 mm (range 15-100 mm). The most common symptoms were headache (51%), dizziness (26%), cranial nerve dysfunction (23%), seizure (22%), nausea and vomiting (18%), and hemiparesis (13%). Surgery was performed in 83% (n = 57). First-line treatments were microsurgical fenestration (n = 30), endoscopic fenestration (n = 15), and cystoperitoneal/ventriculoperitoneal shunting (n = 11). More than one intervention was needed in 42% (n = 24). A particularly high rate of relapse (73%) was observed after endoscopic fenestration, following which 11 patients were admitted for reoperation. By comparison, only eight patients (28%) managed with microsurgical fenestration and four (36%) in the shunted group needed a second surgical procedure. Mean follow-up was 30 months. In the surgical series 79% (n = 45) had a good outcome.We conclude that the surgical treatment of arachnoid cysts has an overall good outcome. In our institution the best results were obtained with microsurgical decompression through craniotomy 6).

References

1)

Hall S, Smedley A, Rae S, Mathad N, Waters R, Chakraborty A, Sparrow O, Tsitouras V. Clinical and radiological outcomes following surgical treatment for intra-cranial arachnoid cysts. Clin Neurol Neurosurg. 2018 Dec 27;177:42-46. doi: 10.1016/j.clineuro.2018.12.018. [Epub ahead of print] PubMed PMID: 30599313.
2)

Saura Rojas JE, Horcajadas Almansa Á, Ros López B. [Microsurgical treatment of intracraneal arachnoid cysts]. Neurocirugia (Astur). 2015 Apr 16. pii: S1130-1473(15)00029-9. doi: 10.1016/j.neucir.2015.02.006. [Epub ahead of print] Spanish. PubMed PMID: 25891259.
3)

Mørkve SH, Helland CA, Amus J, Lund-Johansen M, Wester KG. Surgical Decompression of Arachnoid Cysts Leads to Improved Quality of Life: A Prospective Study. Neurosurgery. 2016 May;78(5):613-25. doi: 10.1227/NEU.0000000000001100. PubMed PMID: 26540351.
4)

Choi JW, Lee JY, Phi JH, Kim SK, Wang KC. Stricter indications are recommended for fenestration surgery in intracranial arachnoid cysts of children. Childs Nerv Syst. 2015 Jan;31(1):77-86. doi: 10.1007/s00381-014-2525-1. Epub 2014 Aug 16. PubMed PMID: 25123786.
5)

Wang C, Liu C, Xiong Y, Han G, Yang H, Yin H, Wang J, You C. Surgical treatment of intracranial arachnoid cyst in adult patients. Neurol India. 2013 Jan-Feb;61(1):60-4. doi: 10.4103/0028-3886.108013. PubMed PMID: 23466842.
6)

Holst AV, Danielsen PL, Juhler M. Treatment options for intracranial arachnoid cysts: a retrospective study of 69 patients. Acta Neurochir Suppl. 2012;114:267-70. doi: 10.1007/978-3-7091-0956-4_52. PubMed PMID: 22327706.

Selective dorsal rhizotomy for spastic diplegia

Selective dorsal rhizotomy (SDR) is often recommended for children with spastic paraparesis and cerebral palsy. SDR reduces spasticity in the lower extremities for these children with spastic paraplegia. However, SDR is infrequently recommended for adults with spasticity. Spastic diplegia in adult patients can be due to stroke, brain or spinal cord injury from trauma, infection, toxic-metabolic disorders, and other causes. Although rarely considered, SDR is an option for adult patients with spastic diplegia as well.

Long-term outcomes of selective dorsal rhizotomy have been promising among the Archer et al., institutional series of patients.

They demonstrated the use of L1-S1 osteoplastic laminoplasty and L1-S1 selective dorsal rhizotomy in a 5-year-old male patient with cerebral palsy and spastic lower extremity diplegia. Favorable selection criteria for this case included disabling lower extremity diplegia, young age, good core strength, no cognitive delay, and strong rehabilitation potential. The patient’s preoperative functional status was noncommunity ambulator (Gross Motor Function Classification System Level III) with walker use and good dynamic balance. Prior to the procedure, he demonstrated an overall decreased muscle strength in bilateral lower extremities with bilateral hamstring spasticity (Modified Ashworth Scale 3) and bilateral heel cord spasticity (Ashworth 4). Rhizotomy was performed with identification and selective sectioning of dorsal nerve roots with abnormal stimulation patterns. Fibers with unsustained discharge of appropriate muscles were identified and spared. No intraoperative or postoperative complications were encountered. The patient had minimal back pain and surgical morbidity postoperatively. Following the procedure and highly structured inpatient and outpatient rehabilitation therapies, the patient exhibited significant improvement in gait velocity (84%) and gait cadence (66%) at 5 months. Additionally, the patient demonstrated greater independence of activities of daily living and improvements in mobility by Pediatric Evaluation Disability Index.Patient consent was obtained from the parent 1).


In a longitudinal study 19 ambulant patients with spastic diplegia due to cerebral palsy (CP) or other causes (mean age at Selective dorsal rhizotomy: 6.6 ± 1.6 years )were assessed four times: pre-Selective dorsal rhizotomy (SDR), 2 years post- SDR, 5 years post-SDR and at least 10 years post-SDR. From 2D video recordings, Edinburgh Visual Gait Score and lower limb joint kinematic parameters were calculated.

Data show that the improvement in the gait pattern obtained short-term after SDR continues during into adolescence and adulthood. Ten years after SDR all patients improved compared to baseline. Considering the lower limb joint kinematics, most notable improvements were found at knee and ankle joints. Compared to the evaluation before SDR, the range of motion of the knee increased: the knee was more extended at initial contact and knee flexion in midswing improved. Excessive ankle plantar flexion was reduced during the entire gait cycle. Only minor changes were found at hip and pelvis. Eight patients underwent additional orthopaedic surgery in the years after SDR, and the present findings should be considered as a combination of SDR, development and additional treatment.

Romei et al., demonstrate lasting improvement of gait quality in ambulant patients with spastic diplegia who underwent SDR during childhood when they become adolescents and young adults 2).


Eppinger et al., describe a patient who underwent a SDR with a successful postoperative outcome. This man suffered a hypertensive and hemorrhagic stroke secondary to intravenous drug abuse at age 46. A SDR was performed after two failed intrathecal baclofen pump placements due to recurrent infections, likely resulting from his immunocompromised status. The patient underwent lumbar laminectomies and dorsal rhizotomies at levels L1-S1 bilaterally. Postoperatively, the patient’s spasticity was significantly reduced. His Ashworth spasticity score decreased from 4/5 to 1/5, and the reduction in tone has been durable over 3 years 3).

References

1)

Archer J, Yaacoub AP, Angulo-Parker F, Fritsch G, Riner S, Coon A, Johnson SK, Delima S, Jea A, Raskin JS. Pre- and Postoperative Gait Analysis and Video for Selective Dorsal Rhizotomy in Spastic Diplegia: 2-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2018 Dec 27. doi: 10.1093/ons/opy392. [Epub ahead of print] PubMed PMID: 30590806.
2)

Romei M, Oudenhoven LM, van Schie PEM, van Ouwerkerk WJR, van der Krogt MM, Buizer AI. Evolution of gait in adolescents and young adults with spastic diplegia after selective dorsal rhizotomy in childhood: A 10 year follow-up study. Gait Posture. 2018 Jun 4;64:108-113. doi: 10.1016/j.gaitpost.2018.06.002. [Epub ahead of print] PubMed PMID: 29894977.
3)

Eppinger MA, Berman CM, Mazzola CA. Selective dorsal rhizotomy for spastic diplegia secondary to stroke in an adult patient. Surg Neurol Int. 2015 Jun 25;6:111. doi: 10.4103/2152-7806.159382. eCollection 2015. PubMed PMID: 26167363; PubMed Central PMCID: PMC4496840.

Transethmoidal encephalocele

Transethmoidal basal encephalocele is a rare condition in adult patients. It is usually diagnosed during childhood by cerebrospinal fluid rhinorrhea, meningitis, a nasal mass, or seizures.

Radovnický et al., from the Masaryk Hospital, Usti nad Labem, Czech Republic, present a case of an adult woman with CSF rhinorrhea following resection of an occipital meningioma. The cribriform plate defect containing the encephalocele was diagnosed by computed tomography and magnetic resonance imaging. Transcranial surgery using a patch was performed successfully. They also discuss the possible pathophysiologic mechanisms of encephalocele and treatment options 1).


Upasani et al., reported the case of a neonate with a transethmoidal encephalocele, who presented with an externally visible intranasal mass at birth. Clinical suspicion of intracranial extension was confirmed by radiological imaging. A bifrontal craniotomy was done to divide the narrow communicating duct. The mass was delivered through the nostril and duraplasty was completed. The postoperative recovery was uneventful 2).


A case of a 3-year-old boy with transethmoidal encephalocele is presented. The patient was found to have bacterial meningitis, which responded well to an intravenous antibiotics therapy. No physical anomaly was evident on examination but plain skull X-ray film showed cloudiness of the left nasal antrum. Coronal CT scan disclosed a defect in the left cribriform plate and soft tissue mass in the left nasal cavity. MRI showed an anterior basal encephalocele protruding into the nasal cavity. Hypothalamic-pituitary system and the optic nerves appeared normal in the sagittal image. CSF rhinorrhea was confirmed by RI cisternography. An operation was performed transcranially. After a left frontal craniotomy, a unilateral bony defect in the cribriform plate and protrusion of the brain was observed subfrontally. The crista galli was intact. The herniated brain substance was transected and partially removed and the bony defect plugged by temporal muscle and covered by lyofirized dura. Microscopic examination of the herniated brain mass revealed gliosis and capillary proliferation. The patient recovered well and there has been no recurrence of CSF rhinorrhea or meningitis. Basal encephalocele is a very rare congenital anomaly. It is reported to constitute 1 to 10% of all encephaloceles. Incidence is estimated as 1 in every 35,000 to 40,000 live births. The anomaly is classified into two subtypes; transethmoidal (TE) and transsphenoidal (TS) 3).


Transsphenoidal and transethmoidal encephaloceles. A review of clinical and roentgen features in 8 cases 4).

References

1)

Radovnický T, Bartoš R, Vachata P, Sameš M. Cerebrospinal Fluid Rhinorrhea due to Transethmoidal Encephalocele Following Occipital Meningioma Resection in an Adult: A Case Report. J Neurol Surg A Cent Eur Neurosurg. 2018 Dec 24. doi: 10.1055/s-0038-1676621. [Epub ahead of print] PubMed PMID: 30583301.
2)

Upasani AV, Patel DN, Chandna SB. A rare presentation of a transethmoidal encephalocele at birth. Pediatr Neonatol. 2014 Oct;55(5):404-6. doi: 10.1016/j.pedneo.2012.12.015. Epub 2013 Feb 4. PubMed PMID: 23597536.
3)

Yoshimoto Y, Noguchi M, Tsutsumi Y. [A case of transethmoidal encephalocele]. No Shinkei Geka. 1992 Mar;20(3):249-54. Review. Japanese. PubMed PMID: 1557174.
4)

Pollock JA, Newton TH, Hoyt WF. Transsphenoidal and transethmoidal encephaloceles. A review of clinical and roentgen features in 8 cases. Radiology. 1968 Mar;90(3):442-53. PubMed PMID: 4966739.

Chiari type 1 deformity Natural History

2 patients with Chiari type 1 deformity progressed in the degree of tonsillar herniation, whereas increasing in prolapse of tonsillar herniation after diagnosis is extremely uncommon.

The first patient aged 17 years was diagnosed with CM-1 in 2009 and was operated due to progression of 5 mm radiologically and worsening symptoms in 2014. The second 5-month-old patient initially showed just low-settled tonsillar localization at the borderline, then it descended by 2 cm when the patient reached 3 years of age, yet could not be operated because of parents’ objection.

Due to lack of reports on increasing tonsillar descent in the literature, these case reports will contribute to natural history and management of CM-1 1).


The natural history of mild symptomatic and asymptomatic CM-1 in adults is relatively benign and nonprogressive; the decision to perform surgical decompression should be based on severity and duration of a patient’s symptoms at presentation. It is reasonable to observe a patient with mild or asymptomatic symptoms even in the presence of significant tonsillar descent or syringomyelia 2).


Strahle et al., identified 147 patients in whom CM-I was diagnosed on MR imaging, who were not offered surgery at the time of diagnosis, and in whom at least 1 year of clinical and MR imaging follow-up was available after the initial CM-I diagnosis. These patients were included in an outcome analysis.

Patients were followed clinically and by MR imaging for a mean duration of 4.6 and 3.8 years, respectively. Of the 147 patients, 9 had new symptoms attributed to the CM-I during the follow-up interval. During this time, development of a spinal cord syrinx occurred in 8 patients; 5 of these patients had a prior diagnosis of a presyrinx state or a dilated central canal. Spontaneous resolution of a syrinx occurred in 3 patients. Multiple CSF flow studies were obtained in 74 patients. Of these patients, 23 had improvement in CSF flow, 39 had no change, and 12 showed worsening CSF flow at the foramen magnum. There was no significant change in the mean amount of cerebellar tonsillar herniation over the follow-up period. Fourteen patients underwent surgical treatment for CM-I. There were no differences in initial cerebellar tonsillar herniation or CSF flow at the foramen magnum in those who ultimately underwent surgery compared with those who did not.

In patients with CM-Is that are selected for nonsurgical management, the natural history is usually benign, although spontaneous improvement and worsening are occasionally seen 3).


Chiari type 1 deformity was incidentally detected on MR images in 11 of 22 patients. The remaining 11 patients had minimal clinical signs at presentation that were not regarded as necessitating immediate surgical treatment. Seventeen patients (77.3%) showed progressive improvement in their symptoms or remained asymptomatic at the last follow-up whereas 5 patients (22.7%) experienced worsening, which was mild in 2 cases and required surgical correction in the remaining 3 cases. On MR imaging a mild reduction in tonsillar herniation was appreciated in 4 patients (18.18%), with complete spontaneous resolution in 1 of these. In 16 patients, tonsillar herniation remained stable during follow-up.

Data confirm the common impression that in both asymptomatic and slightly symptomatic patients with CM-I, a conservative approach to treatment should be adopted with periodic clinical and radiological examinations 4).

References

1)

Börcek AÖ, Aslan A. Unexpected Progression of Tonsillar Herniation in Two Pediatric Cases with Chiari Malformation Type I and Review of the Literature. Pediatr Neurosurg. 2018 Dec 21:1-6. doi: 10.1159/000495066. [Epub ahead of print] PubMed PMID: 30580335.
2)

Langridge B, Phillips E, Choi D. Chiari Malformation Type 1: A Systematic Review of Natural History and Conservative Management. World Neurosurg. 2017 Aug;104:213-219. doi: 10.1016/j.wneu.2017.04.082. Epub 2017 Apr 21. Review. PubMed PMID: 28435116.
3)

Strahle J, Muraszko KM, Kapurch J, Bapuraj JR, Garton HJ, Maher CO. Natural history of Chiari malformation Type I following decision for conservative treatment. J Neurosurg Pediatr. 2011 Aug;8(2):214-21. doi: 10.3171/2011.5.PEDS1122. PubMed PMID: 21806365.
4)

Novegno F, Caldarelli M, Massa A, Chieffo D, Massimi L, Pettorini B, Tamburrini G, Di Rocco C. The natural history of the Chiari Type I anomaly. J Neurosurg Pediatr. 2008 Sep;2(3):179-87. doi: 10.3171/PED/2008/2/9/179. PubMed PMID: 18759599.

Pediatric Chiari type 1 deformity

Epidemiology

Chiari type 1 deformity is commonly seen in pediatric neurology, neuroradiology, and neurosurgery and may have various clinical presentations depending on patient age. In addition, Chiari type 1 deformity is increasingly found by neuroimaging studies as an incidental finding in asymptomatic children 1).

Treatment

The ideal management in children regarding surgical and radiographic decision making is not clearly delineated.

Entezami et al., from the Department of Neurosurgery, AlbanyThomas Jefferson University, , Brown University, Providence, retrospectively reviewed a cohort of patients age 18 years and younger referred to a single neurosurgeon for CM1. Baseline MRIs of the spine were obtained. Non-operative patients had repeat imaging at 6-12 months. Patients who underwent an operation (decompression with/without duraplasty) had repeat imaging at 6 months.

One hundred and thirty-two patients with mean age of 10 years met inclusion criteria. All patients had post-operative symptomatic improvement.

They identified 26 patients with syrinx, 8 with scoliosis, 3 with hydrocephalus, and one had tethered cord. The average tonsillar descent was 8.1 mm in the non-operative group and 11.9 mm in the operative group. Ninety-five patients were managed conservatively (72%). Thirty-seven were offered surgery (28%), and 33 patients underwent intervention; 21 with duraplasty (64%) and 12 without (36%).

Pediatric patients with CM1 require both clinical and radiographic follow-up. Duraplasty may be performed if decompression fails to relieve symptomatology, but is not always needed. CM1 continues to present a challenge in surgical decision making. Adhering to a treatment paradigm may help alleviate difficult decision-making 2).

Chiari malformation Type I (CM-I) related to syndromic craniosynostosis in pediatric patients has been well-studied. The surgical management consists of cranial vault remodeling with or without posterior fossa decompression.

Outcome

Efforts to guide preoperative counseling and improve outcomes research are impeded by reliance on small, single-center studies.

Approximately 1 in 8 pediatric CM-I patients experienced a surgical complication, whereas medical complications were rare. Although complex chronic conditions (CCC) were common in pediatric CM-I patients, only hydrocephalus was independently associated with increased risk of surgical events. These results may inform patient counseling and guide future research efforts 3).

CM-I in children is not a radiologically static entity but rather is a dynamic one. Radiological changes were seen throughout the 7 years of follow-up. A reduction in tonsillar herniation was substantially more common than an increase. Radiological changes did not correlate with neurological examination finding changes, symptom development, or the need for future surgery. Follow-up imaging of asymptomatic children with CM-I did not alter treatment for any patient. It would be reasonable to follow these children with clinical examinations but without regular surveillance MRI 4).

Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms.

Outcome is poor in approximately 3 in 10 patients 5).

The degree of tonsillar herniation has not been a reliable predictor of either symptom severity 6) or surgical outcome 7).

Arnautovic et al. identified 145 operative series of patients with CM-I, primarily from the United States and Europe, and divided patient ages into 1 of 3 categories: adult (> 18 years of age; 27% of the cases), pediatric (≤ 18 years of age; 30%), or unknown (43%). Most series (76%) were published in the previous 21 years. The median number of patients in the series was 31. The mean duration of the studies was 10 years, and the mean follow-up time was 43 months. The peak ages of presentation in the pediatric studies were 8 years, followed by 9 years, and in the adult series, 41 years, followed by 46 years. The incidence of syringomyelia was 65%. Most of the studies (99%) reported the use of posterior fossa/foramen magnum decompression. In 92%, the dura was opened, and in 65% of these cases, the arachnoid was opened and dissected; tonsillar resection was performed in 27% of these patients. Postoperatively, syringomyelia improved or resolved in 78% of the patients. Most series (80%) reported postoperative neurological outcomes as follows: 75% improved, 17% showed no change, and 9% experienced worsening. Postoperative headaches improved or resolved in 81% of the patients, with a statistical difference in favor of the pediatric series. Postoperative complications were reported for 41% of the series, most commonly with CSF leak, pseudomeningocele, aseptic meningitis, wound infection, meningitis, and neurological deficit, with a mean complication rate of 4.5%. Complications were reported for 37% of pediatric, 20% of adult, and 43% of combined series. Mortality was reported for 11% of the series. No difference in mortality rates was seen between the pediatric and adult series 8).

Case reports

A 16-year-old boy who admitted with symptoms related to CM-I. With careful examination and further genetic investigations, a diagnosis of Crouzon syndrome was made, of which the patient and his family was unaware before. The patient underwent surgery for posterior fossa decompression and followed-up for Crouzon’s syndrome.

This is the only case report indicating a late adolescent diagnosis of Crouzon syndrome through clinical symptoms of an associated CM-I 9).

References

1)

Poretti A, Ashmawy R, Garzon-Muvdi T, Jallo GI, Huisman TA, Raybaud C. Chiari Type 1 Deformity in Children: Pathogenetic, Clinical, Neuroimaging, and Management Aspects. Neuropediatrics. 2016 Jun 23. [Epub ahead of print] PubMed PMID: 27337547.
2)

Entezami P, Gooch MR, Poggi J, Perloff E, Dupin M, Adamo MA. Current management of pediatric chiari type 1 malformations. Clin Neurol Neurosurg. 2018 Dec 10;176:122-126. doi: 10.1016/j.clineuro.2018.12.007. [Epub ahead of print] PubMed PMID: 30557765.
3)

Greenberg JK, Olsen MA, Yarbrough CK, Ladner TR, Shannon CN, Piccirillo JF, Anderson RC, Wellons JC 3rd, Smyth MD, Park TS, Limbrick DD Jr. Chiari malformation Type I surgery in pediatric patients. Part 2: complications and the influence of comorbid disease in California, Florida, and New York. J Neurosurg Pediatr. 2016 May;17(5):525-32. doi: 10.3171/2015.10.PEDS15369. Epub 2016 Jan 22. PubMed PMID: 26799408.
4)

Whitson WJ, Lane JR, Bauer DF, Durham SR. A prospective natural history study of nonoperatively managed Chiari I malformation: does follow-up MRI surveillance alter surgical decision making? J Neurosurg Pediatr. 2015 Aug;16(2):159-66. doi: 10.3171/2014.12.PEDS14301. Epub 2015 May 1. PubMed PMID: 25932776.
5)

Aliaga L, Hekman KE, Yassari R, Straus D, Luther G, Chen J, Sampat A, Frim D. A novel scoring system for assessing Chiari malformation type I treatment outcomes. Neurosurgery. 2012 Mar;70(3):656-64; discussion 664-5. doi: 10.1227/NEU.0b013e31823200a6. PubMed PMID: 21849925.
6)

Khan AA, Bhatti SN, Khan G, et al. Clinical and radiological findings in Arnold Chiari malformation. J Ayub Med Coll Abbottabad. 2010;22(2):75-78.
7)

NoudelR,GomisP,SotoaresG,etal.Posteriorfossavolumeincreaseaftersurgery for Chiari malformation type I: a quantitative assessment using magnetic resonance imaging and correlations with the treatment response. J Neurosurg. 2011;115(3): 647-658.
8)

Arnautovic A, Splavski B, Boop FA, Arnautovic KI. Pediatric and adult Chiari malformation Type I surgical series 1965-2013: a review of demographics, operative treatment, and outcomes. J Neurosurg Pediatr. 2015 Feb;15(2):161-77. doi: 10.3171/2014.10.PEDS14295. Epub 2014 Dec 5. PubMed PMID: 25479580.
9)

Canpolat A, Akçakaya MO, Altunrende E, Ozlü HM, Duman H, Ton T, Akdemir O. Chiari Type I malformation yielded to the diagnosis of Crouzon syndrome. J Neurosci Rural Pract. 2014 Jan;5(1):81-3. doi: 10.4103/0976-3147.127885. PubMed PMID: 24741262.

Lipomyelomeningocele

A type of Lipomyeloschisis.

Lipomyelomeningocele, is a closed neural tube defect, taht usually occurs in the lumbosacral area as a single lesion but can be associated with other spinal dysraphism 1) and Caudal regression syndrome.

Represent a unique population within the spectrum of spinal dysraphism.Edit

Pathology

A subcutaneous lipoma that passes through a midline defect in the lumbodorsal fascia, vertebral neural arch, and dura, and merges with an abnormally low tethered cord 2).Edit

Diagnosis

New dynamic MRI-based parameters to establish the presence and magnitude of tethered cord syndrome (TCS) have been defined. oscillatory frequency (OF) measured the extent of loss of translational cord displacement in supine and prone positions; delta bending angle (ΔBA) defined the relative angulation of conus with lower spinal cord, and sagittal and axial root angles represented ventral nerve root stretching. The difference in OF or ΔBA was minimum in the group with thick filum terminale and progressively increased in the groups with lipomyelomeningocele and meningomyelocele 3)Edit

Natural history

The natural history of LMMC remains poorly defined. The description and prevalence of the presenting orthopaedic clinical signs and symptoms for LMMC have been infrequent and often documented only in general terms.Edit

Treatment

Untethering surgery.

An expansile dural graft should be incorporated in cases of lipomyelomeningocele in which primary dural closure does not permit free flow of CSF4).Edit

Case series

In 32 patients with LMMC (21 female and 11 male patients). The majority of patients had their primary tethered cord release (TCR) by ≤1 year of age (59 %), with 22 and 19 % having primary TCR at ages 1-15 and >15 years, respectively. Fifteen patients had at least one repeat TCR, with ten of these having more than one repeat TCR. A significant relationship was noted between low back/radicular pain and repeat TCR (p < 0.001). Ten patients (31%) had a limb length discrepancy of >2.5 cm, and 53 % of patients had asymmetric involvement. Nine patients (28 %) had scoliosis of whom only one required operative treatment. Fifteen patients had foot deformities. Thirteen patients (41 %) had two or more orthopaedic procedures in addition

The presenting musculoskeletal clinical signs and symptoms in patients with LMMC are uniquely different in terms of both pattern and frequency compared to myelomeningocele and other forms of spinal dysraphism.

Its a high prevalence of asymmetrical involvement, a high operative burden, and a high rate of repeat symptomatic tethered cord syndrome requiring TCR. As previously noted by others, TCR in LMMC does not prevent long-term functional deterioration. These findings may be important to our colleagues providing counsel to their patients with LMMC and to their families 5).Edit

Case reports

Fetal lipomyelomeningocele was suspected during the second-trimester ultrasound and confirmed by magnetic resonance imaging. The pregnancy took its course and a term neonate was delivered. At 2 years of age lipomyelomeningocele surgical removal was performed. The patient is now 4 years old and, despite neurogenic bladder, is a healthy boy with normal psychomotor development for his age. This case illustrates the favorable prognosis of this entity and the importance of prompt diagnosis and multidisciplinary counseling 6).Edit

References

Edit1) Hanif H, Khanbabazadeh S, Nejat F, El Khashab M. Tethered cord with tandem lipomyelomeningoceles, split cord malformation and thick filum. J Pediatr Neurosci. 2013 Sep;8(3):204-6. doi: 10.4103/1817-1745.123665. PubMed PMID: 24470813.2) Emery JL, Lendon RG. Lipomas of the Cauda Equina and Other Fatty Tumors Related to Neurospinal Dysraphism.DevMedChildNeurol.1969;11:62–703) Singh S, Behari S, Singh V, Bhaisora KS, Haldar R, Krishna Kumar G, Mishra P, Phadke RV. Dynamic magnetic resonance imaging parameters for objective assessment of the magnitude of tethered cord syndrome in patients with spinal dysraphism. Acta Neurochir (Wien). 2018 Nov 20. doi: 10.1007/s00701-018-3721-7. [Epub ahead of print] PubMed PMID: 30456429.4) Alexiades NG, Ahn ES, Blount JP, Brockmeyer DL, Browd SR, Grant GA, Heuer GG, Hankinson TC, Iskandar BJ, Jea A, Krieger MD, Leonard JR, Limbrick DD Jr, Maher CO, Proctor MR, Sandberg DI, Wellons JC 3rd, Shao B, Feldstein NA, Anderson RCE. Development of best practices to minimize wound complications after complex tethered spinal cord surgery: a modified Delphi study. J Neurosurg Pediatr. 2018 Sep 14:1-9. doi: 10.3171/2018.6.PEDS18243. [Epub ahead of print] PubMed PMID: 30215584.5) Segal LS, Czoch W, Hennrikus WL, Wade Shrader M, Kanev PM. The spectrum of musculoskeletal problems in lipomyelomeningocele. J Child Orthop. 2013 Dec;7(6):513-9. doi: 10.1007/s11832-013-0532-5. Epub 2013 Oct 8. PubMed PMID: 24432115.6) Sarmento-Gonçalves I, Cunha M, Loureiro T, Pinto PS, Ramalho C. Fetal lipomyelomeningocele: A closed neural tube defect diagnosed at second trimester ultrasound examination. J Clin Ultrasound. 2018 Nov 8. doi: 10.1002/jcu.22662. [Epub ahead of print] PubMed PMID: 30411358.

Update: Intentional traumatic brain injury

Intentional traumatic brain injury

Epidemiology

Intentional injury has been associated with certain demographics and socioeconomic groups. Less is known about the relationship of intentional traumatic brain injury (TBI) to injury severity, mortality, and demographic and socioeconomic profile.


A planned secondary analysis of a prospective multicentre cohort study was conducted in 10 emergency departments EDs in Australia and New Zealand, including children aged <18 years with head injury (HI). Epidemiology codes were used to prospectively code the injuries. Demographic and clinical information including the rate of clinically important traumatic brain injury (ciTBI: HI leading to death, neurosurgery, intubation >1 day or admission ≥2 days with abnormal computed tomography [CT]) was descriptively analysed.

Intentional injuries were identified in 372 of 20 137 (1.8%) head-injured children. Injuries were caused by caregivers (103, 27.7%), by peers (97, 26.1%), by siblings (47, 12.6%), by strangers (35, 9.4%), by persons with unknown relation to the patient (21, 5.6%), other intentional injuries (8, 2.2%) or undetermined intent (61, 16.4%). About 75.7% of victims of assault by caregivers were <2 years, whereas in other categories, only 4.9% were <2 years. Overall, 66.9% of victims were male. Rates of CT performance and abnormal CT varied: assault by caregivers 68.9%/47.6%, by peers 18.6%/27.8%, by strangers 37.1%/5.7%. ciTBI rate was 22.3% in assault by caregivers, 3.1% when caused by peers and 0.0% with other perpetrators.

Intentional HI is infrequent in children. The most frequently identified perpetrators are caregivers and peers. Caregiver injuries are particularly severe 1).


A study identified 1,409 (8.0%) intentional TBIs and 16,211 (92.0%) unintentional TBIs. Of the intentional TBIs, 389 (27.6%) was self-inflicted TBI (Si-TBI) and 1,020 (72.4%) was other-inflicted TBI (Oi-TBI). The most common cause of Si-TBI was “jumping from high places” (32.1%), followed by “firearms” (30.6%). About half of Oi-TBI was because of “fight and brawl” (48.3%), followed by “struck by objects” (26.1%). Si-TBI was associated with younger age, female gender, and having more alcohol/drug abuse history. For Oi-TBI, younger age, male gender, having more alcohol/drug abuse history were independently associated.

This research provides the first comprehensive overview of intentional TBI based in Canada.

The comprehensive data set (CDS) of the Ontario trauma registry (OTR) provided the ability to identify who is at risk for intentional TBI. Prevention programs and more targeted rehabilitation services should be designed for this vulnerable population 2).

Outcome

Intentional injury is associated with significant morbidity and mortality.

Caregiver injuries are particularly severe in children 3).

Prospective data were obtained for 2,637 adults sustaining TBIs between January 1994 and September 1998. Descriptive, univariate, and multivariate analyses were conducted to determine the predictive value of intentional TBI on injury severity and mortality.

Gender, minority status, age, substance abuse, and residence in a zipcode with low average income were associated with intentional TBI. Multivariate analysis found minority status and substance abuse to be predictive of intentional injury after adjusting for other demographic variables studied. Intentional TBI was predictive of mortality and anatomic severity of injury to the head. Penetrating intentional TBI was predictive of injury severity with all injury severity markers studied.

Many demographic variables are risk factors for intentional TBI, and such injury is a risk factor for both injury severity and mortality. Future studies are needed to definitively link intentional TBI to disability and functional outcome 4).

References

1) , 3)

Babl FE, Pfeiffer H, Dalziel SR, Oakley E, Anderson V, Borland ML, Phillips N, Kochar A, Dalton S, Cheek JA, Gilhotra Y, Furyk J, Neutze J, Lyttle MD, Bressan S, Donath S, Hearps SJ, Crowe L; Paediatric Research in Emergency Departments International Collaborative (PREDICT). Paediatric intentional head injuries in the emergency department: A multicentre prospective cohort study. Emerg Med Australas. 2018 Nov 26. doi: 10.1111/1742-6723.13202. [Epub ahead of print] PubMed PMID: 30477046.
2)

Kim H, Colantonio A. Intentional traumatic brain injury in Ontario, Canada. J Trauma. 2008 Dec;65(6):1287-92. doi: 10.1097/TA.0b013e31817196f5. PubMed PMID: 19077615.
4)

Wagner AK, Sasser HC, Hammond FM, Wiercisiewski D, Alexander J. Intentional traumatic brain injury: epidemiology, risk factors, and associations with injury severity and mortality. J Trauma. 2000 Sep;49(3):404-10. Erratum in: J Trauma 2000 Nov;49(5):982. PubMed PMID: 11003315.
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