Brainstem Injury Research Articles

The importance of axonal directions in the brainstem injury during neurosurgical interventions.

Brainstem, which connects the distal part of the brain and the spinal cord, contains main motor and sensory nerves and facilitates communication between the cerebrum, cerebellum, and spinal cord. Due to the complicated anatomy and neurostructure of brainstem, surgical interventions to resect brainstem tumors are particularly challenging, and new approaches to reduce the risk of surgical brain injury are of utmost importance. Although previous studies have investigated the structural anisotropy of brain white matter, the effect of axonal fibers on the mechanical properties of white matter has not yet been fully understood. The current study aims to compare the effect of axonal orientation on changes in material properties of brainstem under large deformations and failure through a novel approach. Using diffusion tensor imaging (DTI) on ex-vivo bovine brains, we determined the orientation of axons in brainstem. We extracted brainstem samples in two orthogonal directions, parallel and perpendicular to the axons, and subjected to uniaxial tension to reach the failure at loading rates of 50mm/min and 150mm/min. The results showed that the tearing energy and failure strain of samples with axons parallel to the force direction were approximately 1.5 times higher than the samples with axons perpendicular to the force direction. The results also revealed that as the sample's initial length increases, its failure strain decreases. These results emphasize the importance of the axon orientation in the mechanical properties of brainstem, and suggest that considering the directional-dependent behavior for this tissue could help to propose new surgical interventions for reducing the risk of injury during tumor resection.

Near Total Versus Gross Total Resection of Large Vestibular Schwannomas: Facial Nerve Outcome.

Large vestibular schwannomas (VSs) with brainstem compression are generally reserved for surgical resection. Surgical aggressiveness must be balanced with morbidity from cranial nerve injury. The purpose of the present investigation is to evaluate the clinical presentation, management modality, and patient outcomes following near total resection (NTR) vs gross total resection (GTR) of large VSs. To assess facial nerve outcome differences between GTR and NTR patient cohorts. Between January 2010 and March 2018, a retrospective chart review was completed to capture patients continuously who had VSs with Hannover grades T4a and T4b. NTR was decided upon intraoperatively. Primary data points were collected, including preoperative symptoms, tumor size, extent of resection, and postoperative neurological outcome. A total of 37 patients underwent surgery for treatment of large and giant (grade 4a and 4b) VSs. Facial nerve integrity was preserved in 36 patients (97%) at the completion of surgery. A total of 27 patients underwent complete resection, and 10 had near total (>95%) resection. Among patients with GTR, 78% (21/27) had House-Brackmann (HB) grade I-II facial nerve function at follow-up, whereas 100% (10/10) of the group with NTR had HB grade I-II facial nerve function. Risk of meningitis, cerebrospinal fluid leak, and sinus thromboses were not statistically different between the 2 groups. There was no stroke, brainstem injury, or death. The mean follow-up was 36 mo. NTR seems to offer a benefit in terms of facial nerve functional outcome compared to GTR in surgical management of large VSs without significant risk of recurrence.

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy.

Cardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hypercaloric diet. Two low-dose streptozotocin injections were used to evoke a state of late decompensated T2D. Cardiac autonomic function was assessed by invasive measurement of baroreflex sensitivity using the vasoactive method. Progression into T2D was associated with aggravation of CAN to include both sympathetic and parasympathetic arms. Unlike prediabetic rats, T2D rats showed markers of brainstem neuronal injury and inflammation as well as increased serum levels of IL-1β. Experiments on PC12 cells differentiated into sympathetic-like neurons demonstrated that brainstem injury observed in T2D rats resulted from exposure to possible proinflammatory mediators in rat serum rather than a direct effect of the altered metabolic profile. CAN and the associated cardiovascular damage in T2D only responded to combined treatment with insulin to manage hyperglycemia in addition to a nonhypoglycemic dose of metformin or pioglitazone providing an anti-inflammatory effect, coincident with the effect of these combinations on serum IL-1β. Our present results indicate that CAN worsening upon progression to T2D involves brainstem inflammatory changes likely triggered by systemic inflammation.

End-Tidal Carbon Dioxide Impacts Brain and Kidney Injury in Experimental Extracorporeal Cardiopulmonary Resuscitation (ECPR).

Extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation (ECPR) is proposed for cardiac resuscitation in selected cases. End-tidal carbon dioxide (ETCO2) is easily obtained during conventional cardiopulmonary resuscitation (CPR). We hypothesized that the level of ETCO2 during CPR would reflect the degree of brain and kidney damage following ECPR in experimental refractory cardiac arrest. Ventricular fibrillation was induced in 10 pigs, followed by mechanical CPR for 45 min and thereafter ECPR for 180 min. Blood- and urine-samples, physiologic parameters, and histopathology of brain and kidney were analyzed. Animals were divided into Group High (GHigh) and Group Low (GLow) according to value of ETCO2 (10 mm Hg) at the end of CPR. Carotid blood pressure and blood flow declined over time in both groups during CPR but was higher in GHigh. Coefficient of determination for ETCO2 and carotid blood flow was substantial (r2 = 0.62). The oxygen delivery index was higher for GHigh 444 (396-485) L/min/m2 as compared with GLow at 343 (327-384) L/min/m2 (P = 0.02) at the end of ECPR. Also, P-S100B were lower in GHigh, (P < 0.05) and GLow demonstrated worse histopathological injury in central parts of the brain (P < 0.01). During ECPR, urinary output was higher in GHigh (P < 0.05). Kidney injury marker Plasma Neutrophil Gelatinae-associated Lipocalin increased in both groups during ECPR but was more pronounced in GLow (P = 0.03). Renal histopathology revealed no difference between groups. ETCO2 at the end of mechanical CPR is inversely associated with extent of brainstem and renal injury following ECPR.

Brainstem iron overload and injury in a rat model of brainstem hemorrhage

Background and PurposeBrainstem hemorrhage (BSH) is the most devastating subtype of intracerebral hemorrhage (ICH) with the highest mortality ranging from 56 % to 61.2 %. However, there is no effective medical or surgical therapy to improve its outcomes in clinic to date due to lack of understanding of its injury mechanisms. Herein, we explored the brainstem iron overload and injury in a rat model of BSH. MethodsNeurological scores were examined on day 1, 3, and 7 after modeling, and mortality of the rats was recorded to draft a survival curve. Rats were monitored by MRI using T2 and susceptibility weighted imaging (SWI) before sacrifice for examination of histology and immunofluorescence on day 1, 3, and 7. ResultsBSH rats had a high mortality of 56 % and demonstrated the severe neurological deficits mimicking the clinical conditions. SWI showed that the same increasing tendency in change of hypointense area with that in iron deposition by Perls staining from day 1 to 7. Expression of heme oxygenase 1 (HO-1) and generation of reactive oxygen species (ROS) had similar tendency and both peaked on day 3. Neuronal degeneration occurred and stayed elevated from day 1 to 7, while myelin sheath injury was initially observed on day 1 but without significant difference within 7 days. Conclusions: The time courses of erythrocyte lysis, HO-1 expression, iron deposition and ROS generation are related to each other after BSH. Besides, brainstem injury including neuronal degeneration and myelin damage were observed and discussed.

Efficacy and Safety of Monoclonal Antibody Therapy in Neuromyelitis Optica Spectrum Disorders: Evidence from Randomized Controlled Trials

Background: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory disorders in central nervous system (CNS) characterized by symptoms of optic nerve, spinal cord, brainstem and cerebrum injuries. Recent studies have shown that monoclonal antibodies (Rituximab, Eculizumab, Inebilizumab, Satralizumab, etc.) were effective for the treatment of NMOSD. We performed a meta-analysis to evaluate the efficacy and safety of these monoclonal antibodies in NMOSD. Methods: The MEDLINE, EMBASE, Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov database were searched for randomized controlled trials (RCTs) which had assessed the therapy of monoclonal antibody in NMOSD patients. Results: We pooled 524 (monoclonal antibody group, n = 344 and placebo group, n = 180) from 4 RCTs and 444 patients (84.7%) were AQP4-IgG seropositive. Monoclonal antibody therapy reduced annualized relapse rate (mean -0.27, 95% CI, -0.36 to -0.18, P <0.0001), on-trial relapse risk (RR 0.25, 95% CI 0.12 to 0.52, P = 0.0003), EDSS (Expanded disability status scale) score (mean -0.51, 95% CI, -0.92 to -0.11, P = 0.01) and serious adverse events (RR 0.59, 95% CI 0.37 to 0.96, P = 0.03) but didn't show any significant differences in total adverse events or mortality. In the subgroup analysis, we found that comparing with other monoclonal antibodies, Eculizumab might be more effective in decreasing on-trial relapse risk (Chi2 =9.84, P =0.002) for AQP-4 positive patients. Conclusions: Monoclonal antibody therapy was effective and safe in NMOSD treatment. More RCTs were expected to assess monoclonal antibodies in NMOSD.

COVID-19: Coronavirus replication, pathogenesis, and therapeutic strategies.

The frequency, distribution, and appearance of corpus callosum injuries were evaluated with MR and CT in a prospective study of 78 patients with acute (n = 63) and chronic (n = 15) head injuries. Traumatic lesions of the corpus callosum were detected in 47% of patients. MR was significantly (p less than .001) more sensitive than CT in the detection of callosal injuries. MR and CT visualized 100% and 27%, respectively, of the traumatic callosal lesions that were detected in the study population. The majority of lesions were located in the splenium but a few were also found in the body and genu. Patients with callosal injuries had a significantly higher incidence of primary brainstem injury (p less than .02) as well as a greater number of subcortical gray-matter (p less than .05) and diffuse axonal "shear" (p less than .001) lesions. In addition, patients with callosal injuries had a significantly higher incidence of traumatic lesions of the septum pellucidum (p less than .007) and fornix (p less than .001). Intraventricular hemorrhage occurred significantly more often (p less than .002) in patients with callosal injuries, especially if traumatic lesions of the fornix or septum pellucidum were also present. Patients with callosal injuries had significantly lower initial Glasgow Coma Scale scores (mean, 6.6) than those without injuries (mean, 10.7) (p less than .001). Injury to the corpus callosum occurs much more often with nonfatal head injuries than had been believed previously.

Identification of separation phenomenon during brain death determination of potential organ donor and analysis of relative factors

Background: With analyzing the incongruent phenomenon of electrical active and cerebral blood flow in brain death determination and screening the related factors, offer correct explanations and countermeasure to ensure the successful implementation of donation after brain death.Methods: Relevant clinical data of potential brain death organ donors were prospectively collected between June 2018 and May 2019. The related parameters of neurological examination, laboratory examination and neuroimaging examination during the period of brain death determination were dynamically recorded. Separation phenomenon was used as grouping factors to screen the factors related to separation phenomena through univariate and multivariate analysis.Results: According to the inclusion criteria, 127 patients were included in the study. Among 22 patients (17.3%) with incongruent phenomenon, 17 (77.3%) had electrical silence earlier than cerebral blood flow arrest, and 9 (22.7%) had cerebral blood flow arrest earlier than electrical silence. Univariate and multivariate analysis showed that age &lt;14 years (OR=6.25, 95%CI 1.21-32.22, p=0.028), SBP≥140 mmHg (OR=7.43, 95%CI 1.62-33.99, p=0.010), primary brainstem injury (OR=15.89, 95%CI 3.04-82.93, p=0.006), spontaneous respiratory arrest time ≤72 hours (OR=11.96, 95%CI 1.59-89.78, p=0.009) and decompression craniotomy(unilateral or bilateral) (OR=16.28, 95%CI 2.25-117.73, p=0.001) were associated with separation phenomenon..Conclusions: Separation phenomenon is a common during the confirmation test of brain death determination in China, and should be correctly recognized. To adopt corresponding measures according to risk factors is useful for successful implementation of donation after brain death.

Research progress on mechanism and dosimetry of brainstem injury induced by intensity-modulated radiotherapy, proton therapy, and heavy ion radiotherapy.

Radiotherapy (RT) is an effective method for treating head and neck cancer (HNC). However, RT may cause side effects during and after treatment. Radiation-induced brainstem injury (BSI) is often neglected due to its low incidence and short survival time and because it is indistinguishable from intracranial tumor progression. It is currently believed that the possible mechanism of radiation-induced BSI includes increased expression of vascular endothelial growth factor and damage of vascular endothelial cells, neurons, and glial cells as well as an inflammatory response and oxidative stress. At present, it is still difficult to avoid BSI even with several advanced RT techniques. Intensity-modulated radiotherapy (IMRT) is the most commonly used therapeutic technique in the field of RT. Compared with early conformal therapy, it has greatly reduced the injury to normal tissues. Proton beam radiotherapy (PBT) and heavy ion radiotherapy (HIT) have good dose distribution due to the presence of a Bragg peak, which not only results in better control of the tumor but also minimizes the dose to the surrounding normal tissues. There are many clinical studies on BSI caused by IMRT, PBT, and HIT. In this paper, we review the mechanism, dosimetry, and other aspects of BSI caused by IMRT, PBT, and HIT.Key Points• Enhanced MRI imaging can better detect radiation-induced BSI early.• This article summarized the dose constraints of brainstem toxicity in clinical studies using different techniques including IMRT, PBT, and HIT and recommended better dose constraints pattern to clinicians.• The latest pathological mechanism of radiation-induced BSI and the corresponding advanced treatment methods will be discussed.

A Prospective 10-Year Observational Study of Reduction of Radiation Therapy Clinical Target Volume and Dose in Early-Stage Nasopharyngeal Carcinoma

Current guideline recommends a uniform method of delineation of subclinical disease within the primary clinical target volume (CTVp) for all stages of nasopharyngeal carcinoma (NPC). We performed a prospective observational study to investigate the outcomes with a reduced CTVp and radiation dose for early-stage NPC. Patients with newly diagnosed, biopsy-proven World Health Organization type II-III and American Joint Committee on Cancer/Union for International Cancer Control sixth edition stage T1-2N0-1 disease were enrolled. All patients were treated with intensity modulated radiation therapy alone. We categorized CTVp into CTVp1 (high risk) and CTVp2 (low risk). CTVp1 comprised of gross tumor (on magnetic resonance imaging or contrast-enhanced computed tomography) plus a 5-mm margin (3-mm posteriorly) and was prescribed to 60 Gy in 30 fractions (fr). CTVp2 was generated from CTVp1 plus a 5-mm margin (3 mm posteriorly), excluding the maxillary and cavernous sinuses, and was prescribed to 54 Gy in 30 fr. The prescribed doses to the primary and nodal gross tumor volume (GTVp and GTVn) were 68 Gy in 30 fr and 60 to 66 Gy in 30 fr, respectively. Primary endpoint was local recurrence-free survival. This study was registered in ClinicalTrials.gov, number NCT03839602. From May 2001 to August 2006, 103 patients were recruited and completed IMRT. With a median follow-up of 15.2 years (range, 2.1-18.1 years), only 1 patient had local failure. Ten-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, and overall survival were 90.3%, 88.3%, 90.3%, and 91.2%, respectively. Among late IMRT-related adverse events, we recorded 2 patients with G1 cranial nerve injury, 3 patients with G3 hearing loss, and 3 patients with G3 subcutaneous fibrosis. No patients had temporal lobe necrosis, brain stem injury, or trismus. Decreased CTV margins and radiation doses can achieve long-term tumor control with mild late toxicities for patients with early-stage NPC.

Bilateral Facial Nerve Palsy following Head Injury: A Report of Two Uncommon Cases

AbstractBilateral facial nerve palsy (FNP) following head injury without any brain parenchymal injury or brain stem injury is quite an uncommon presentation. We came across two baffling cases of head trauma in which the patients developed simultaneous bilateral lower motor FNPs without any significant findings in initial brain scans which would suggest the pathophysiology for such a condition. Both the cases were found to be having longitudinal fractures of the temporal bone leading to injury of the facial nerves bilaterally. After conservative management, both the cases showed appreciable neurological improvement on follow-up. Hence, although bilateral FNP can be a diagnostic dilemma, it is quite possible to precisely localize the site of injury and successfully treat it.

Prognostic factors in craniocerebral gunshot wounds: Analysis of 30 patients from the neurosurgical viewpoint.

Craniocerebral gunshot wounds (CGW) are the most lethal injuries of the cranium. CGW is mostly secondary to military conflicts but may also be seen in civilian life. These injuries also have severe consequences, such as epilepsy, hydrocephalus, infection and late-term cognitive dysfunctions. The present study aims to present our series of CGW and to discuss the prognostic factors and consequences of these injuries. The data of patients who were treated in our department for CGW between 2011 and 2019 were retrospectively reviewed in this study. The injury type, wounding site, surgical management and outcomes were analyzed. Radiological evaluation was also performed. Thirty patients were treated with the diagnosis of CGW. All of the patients were male and the mean age was 27.9 years. The frontal lobe was affected in 12 (40%) patients, while temporal lobe in eight, occipital lobe in six, parietal lobe in three, and posterior fossa in one patients. Twenty-three patients underwent surgical treatment, seven patients were treated conservatively. Thirteen (43.3%) patients died despite the treatment. Mortality in CGW is high. Ventricular injuries, bihemispheric or midline injuries, perforating injuries, brain stem injuries and low GCS score at admission are prognostic factors for CGW. Appropriate management is mandatory to obtain a better clinical outcome.

Feasibility of Pupillometry-Based Indices to Assess Nociception in Sedated Critically Ill Patients.

To the Editor We have read with interest the article by Vinclair et al.1 We appreciate the research study done by the esteemed authors, as we also use pupillometer in our clinical practice. Patients on treatment with drugs that were known to alter pupil reflex dilation measurements were excluded from the study. It was noted that for sedation, the patients received continuous infusions of midazolam or propofol, sufentanil, and ketamine at the discretion of the physician in charge.1 Also, the doses of sufentanil were higher in the brain-injured group than in the non–brain-injured group. Rouche et al2 studied the effects of depth of sedation on pupillometry indices in mechanically ventilated patients. They compared the maximum contraction velocity of the pupil (Vmax) and variation in pupil diameter (PD) among 3 groups of patients based on the levels of sedation by evaluating the of bispectral index (BIS). The groups were classified as patients under heavy sedation (<40), acceptable sedation (40–60), and light sedation (>60) based on BIS values. There was a significant difference in Vmax between the heavily sedated and the acceptable groups (P < .0001) and also a significant difference in the variation of PD (P < .0001) between the groups.2 Similarly, there was a significant difference in Vmax (P < .0001) and variation in PD (P < .0001) between heavy sedation and light sedation groups.2 Gaillard et al3 evaluated the pupillary dilation reflex (PDR), to a noxious stimulus, for predicting analgesic level before endotracheal suctioning of mechanically ventilated patients under a deep level of sedation by applying tetanic stimulations of 10, 20, 40, and 60 mA.3 There was no significant difference in the area under the receiver operating characteristic (ROC) curves between different intensity levels. It was also noted that the PDR never exceeded 0.6 even with the highest stimulation.3 In the present study, the authors have not mentioned the level of sedation of the patients, and this could have contributed to possible bias in their study. In the present study, the authors found that pupillary pain index measurements during tetanic stimulation positively correlated with behavioral pain scale responses to endotracheal suctioning. However, the authors did not analyze the correlation with the behavioral pain scale during tetanic stimulation. Tetanic stimulation and endotracheal suctioning are 2 different noxious stimuli as one is a central stimulus carried by the cranial nerves, whereas the latter is a peripheral stimulation via the spinal cord. Though the authors have excluded patients with bilateral mydriasis, which happens at a later stage of brain herniation, they did not exclude patients with other pupillary abnormalities. Patients at early stages of uncal herniation will have unilateral mydriasis and patients with mild brain injury can present with sluggish pupillary responses.4 Similarly, the patients with brainstem injury could present with varied pupillary responses, the most notable being the pinpoint pupils encountered in pontine injury.4 We want to point out that there had been no mention of these clinical presentations and the assessment of pupillometry in such patients could result in erroneous findings. Aishvarya Shree Nedunchezhian, MDNeeraja Ajayan, MDAjay Prasad Hrishi, MD, DNB, DMDivision of NeuroanesthesiaDepartment of AnaesthesiologySree Chitra Tirunal Institute for Medical SciencesThiruvananthapuram, Kerala, India[email protected]

Delayed Diagnosis of Transnasal Penetrating Brain Stem Injury Caused by a Metallic Parasol Hanger

Delayed Diagnosis of Transnasal Penetrating Brain Stem Injury Caused by a Metallic Parasol Hanger

5-Fluorouracil Combined with Cisplatin Via Arterial Induction for Advanced T-Stage Nasopharyngeal Carcinoma: A 10-Year Outcome Study

The aim of this study was to determine the efficacy, late adverse events, and 10-year survival outcome of 5-fluorouracil administered continuously for 120 h combined with cisplatin via a superficial temporal artery in patients with advanced T-stage nasopharyngeal carcinoma (NPC). Forty-five patients with histologically confirmed advanced T-stage NPC were eligible for inclusion in this clinical trial. The patients received induction chemotherapy consisting of cisplatin (20 mg/m2/d for 1–5 d) and 5-fluorouracil, administered continuously for 120 h at different dose gradients(200-500mg/m2/d) via a superficial temporal artery. Following two cycles of induction chemotherapy, radical radiotherapy was commenced. We assessed the efficacy, survival, toxicity, and quality of life of patients following treatment, especially in terms of oral mucositis and radiation-induced brain damage. The overall response (complete response + partial response) rates following induction chemotherapy in the primary mass and lymph nodes were 100% and 100%, respectively. The maximum tolerated dose(MTD) of 5-Fluorouracil was 450mg/m2,we also determined the optimal dose was 400mg/m2 according to the response, toxicities and survival. All 45 (100%) patients achieved down-staging of T-category after induction chemotherapy. No late neurological toxicities, such as brain stem injury, temporal lobe necrosis, and spinal cord injury, were observed. The 5-year and 10-year overall survival (OS) rates were 79% and 64.7%, with a median OS of 128 months. 5-Fluorouracil continuous infusion combined with cisplatin via a superficial temporal artery showed promising survival and low toxicities in patients with advanced T-stage NPC.

Universal Brain-Machine Interfaces Enabled By Flexible Scalp Electronics and Deep Convolutional Neural Networks

Electroencephalography (EEG) allows non-invasive monitoring of brain electrical activity at a fine temporal resolution. However, it is difficult to consistently capture high-quality biopotential signals due to natural variations in scalp and skin conditions. Conventional EEG systems suffer from inconsistent signal quality extensive preparation time, and uncomfortable and bulky electrode setups from long, inflexible wires and rigid electrodes. Improvements in analysis and machine learning techniques have allowed researchers to extract more information from EEG with fewer electrodes on the scalp with certain EEG paradigms. However, further hardware improvements would be required before these systems could be comfortably used daily. Here, we introduce skin-like hybrid electronics (SKINTRONICS), a fully portable, wireless, flexible biomonitoring electronics platform incorporating a soft elastomeric membrane for maximum conformability and wearability on the skin. This concept allows for a comfortable and ergonomic wearable BMI concept that can be used long-term without discomfort and is optimized for use in a rehabilitation setting for patients with brainstem injury or other motor impairment. Analytical and computational studies establish the fundamental design criteria of the SKINTRONICS, enabling seamless portable EEG recording with significantly enhanced signal quality over commercial systems. Analysis in the time domain and frequency domain are completed, with deep convolutional neural networks providing appreciable improvements over conventional techniques such as SVM. The real-time time-domain analysis with deep convolutional neural networks allows for highly accurate classification and fine machine control with high information transfer rates from only two channels. With six human subjects this wireless interface achieves a high accuracy (94.54% ± 0.90%) for a corresponding information transfer rate of 122.1 ± 3.53 bits per minute, demonstrated using a wireless wheelchair, motorized vehicle, and keyboard-less presentation using a two-channel EEG. This demonstrates great potential for this platform, which can accommodate a wide range of assistive technologies as well as different EEG paradigms like motor imagery (MI).

Brainstem Injury in Pediatric Patients Receiving Posterior Fossa Photon Radiation

Brainstem necrosis is a rare, but dreaded complication of radiation therapy; however, data on the incidence of brainstem injury for tumors involving the posterior fossa in photon-treated patient cohorts are still needed. Clinical characteristics and dosimetric parameters were recorded for 107 pediatric patients who received photon radiation for posterior fossa tumors without brainstem involvement from 2000 to 2016. Patients were excluded if they received a prescription dose <50.4 Gy, a brainstem maximum dose <50.4 Gy, or had fewer than 2 magnetic resonance imaging scans within 18 months after radiation. Post-radiation therapy magnetic resonance imaging findings were recorded, and brainstem toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version5. The most common histologies were medulloblastoma (61.7%) and ependymoma (15.9%), and median age at diagnosis was 8.3 years (range, 0.8-20.7). Sixty-seven patients (62.6%) received craniospinal irradiation (median, 23.4 Gy; range, 18.0-39.6) as a component of their radiation therapy, and 39.3% and 40.2% of patients received an additional involved field or whole posterior fossa boost, respectively. Median prescribed dose was 55.8 Gy (range, 50.4-60.0). Median clinical and imaging follow-up were 4.7 years (range, 0.1-17.5) and 4.2 years (range, 0.1-17.3), respectively. No grade ≥2 toxicities were observed. The incidence of grade 1 brainstem necrosis was 1.9% (2 of 107). These patients were by definition asymptomatic and experienced resolution of imaging abnormality after 5.3 months and 2.1 years, respectively. Risk of brainstem necrosis was minimal in this multi-institutional study of pediatric patients treated with photon radiation therapy for tumors involving the posterior fossa with no cases of symptomatic brainstem injury, suggesting that brainstem injury risk is minimal in patients treated with photon therapy.

Brainstem injury in victims of sudden intrauterine death syndrome (SIUDS) and sudden infant death syndrome (SIDS)

Introduction: Sudden intrauterine death syndrome (SIUDS) and sudden infant death syndrome (SIDS) are often associated in a single pathology, resulting from an unexpected fetal or infant injury. Among the various causes, the action of external toxics, still current in the West, should not be excluded. The present histopathological observations indicate the brainstem nuclei as possible neuronal targets of toxic substances; these cause direct damage to cells, including those at the mitochondrial level, as well as indirect functional impairment. During fetal life in utero, the placenta does not act as a total filter; rather it proves permeable to toxics which are able to penetrate the hematoencephalic barrier which shields the fetus. Clinical tests have yet to be devised which reliably signal impending danger of unexpected fetal or infant injury from external toxics.

Cinical and ENMG findings in patients with rare variants of Guillain Barré Syndrome

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most recognized form of Guillain Barré Syndrome (GBS), while others variants such as Miller-Fisher syndrome (MFS) and pharyngo-cervico-brachial (PCB) variant are less recognized. To describe rare variants of GBS. Clinical and paraclinical data were reviewed. Our patients were respectively 8 and 38 years-old. The first patient presented for walk disturbance and the second one for swallowing disorders. At neurological examination, our first case presented ophtalmoplegia, right peripheral facial palsy, areflexia and proprioceptive ataxia. The other yielded areflexia, ataxia and palsy of the ninth, tenth and eleventh cranial nerves. Brain and spinal MRI showed radicular enhancement in the last root in our first case. Lumbar puncture revealed albumino-cytological dissociation in only one case. Electroneuromyography (ENMG) matched with the diagnosis of AIDP with mainly sensory axonal loss in the first case and motor demyelinating damage in the second case. The diagnosis was consistent with MFS in the first case and PCB variant of GBS in the second one. The PCB and MFS variant are rare forms of GBS. Ataxia commonly described in both of our cases may lead to overlapping syndrome and supports the view that PCB and MFS belongs to a continuous spectrum. Ataxia makes also difficult to differentiate these clinical entities from brainstem injury. However, areflexia and ENMG help to make the diagnosis. Further studies are needed to clarify whether these entities have specific patterns in electrophysiological studies.

Influence of Foramen Magnum Boundary Condition on Intracranial Dynamic Response Under Forehead Impact Using Human Body Finite Element Model

The biofidelity is an essential requirement of the application of human head finite element (FE) models to investigate head injuries under mechanical loadings. However, the influence of the foramen magnum boundary condition (FMBC) on intracranial dynamic responses under head impacts has yet to be fully identified until now. This study aimed to investigate the effect of different modeling methods of the FMBC on intracranial dynamic responses induced by forehead impact, especially the axonal injury associated dynamic responses. The total human model for safety (THUMS) was applied in this study. Two FE models with different FMBC modeling methods were developed from the THUMS model. Then, three forehead impact FE models were established respectively, including the original THUMS model. Further FE simulations were conducted to investigate the influence of FMBC modeling methods on intracranial dynamic responses. Though, difference between the intracranial dynamic responses (relative skull-brain motion and strain responses) at areas far from the foramen magnum were slightly, the corresponding difference at the brain stem area were distinctly. Meanwhile, the predicted axonal injury risk of the brain stem white matter was varying among each other. Different modeling methods of FMBC could result in different intracranial dynamic responses of the brain stem, and affect the axonal injury prediction. Therefore, the modeling of the FMBC should be further evaluated for the study of brain stem injury using human head FE models.