Juvenile Traumatic Brain Injury Results in Cognitive Deficits Associated with Impaired Endoplasmic Reticulum Stress and Early Tauopathy.

The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF)-1α was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1α was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso-ciated with the activation of a known tau kinase, glycogen synthase kinase-3ß (GSK-3ß), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short-term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the course of 30 days, and that they had significant short-term and spatial memory deficits following injury.

Biallelic PMS2 Mutation and Heterozygous DICER1 Mutation Presenting as Constitutional Mismatch Repair Deficiency With Corpus Callosum Agenesis: Case Report and Review of Literature.

Constitutional mismatch repair deficiency syndrome is a cancer predisposition syndrome caused by autosomal recessive biallelic (homozygous) germline mutations in the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). The clinical spectrum includes neoplastic and non-neoplastic manifestations. We present the case of a 7-year-old boy who presented with T-lymphoblastic lymphoma and glioblastoma, together with non-neoplastic manifestations including corpus callosum agenesis, arachnoid cyst, developmental venous anomaly, and hydrocephalus. Gene mutation analysis revealed pathogenic biallelic mutations of PMS2 and heterozygous DICER1 variant predicted to be pathogenic. This report is the first to allude to a possible interaction of the mismatch repair system with DICER1 to cause corpus callosum agenesis.

Multiple calcifying pseudoneoplasms of the neuraxis.

Calcified pseudoneoplasms of the neuraxis (CAPNON) are a rare diagnostic entity. They have been reported intra-cranially as well as in the spine, and are most commonly found at the skull base. This is a case report of a 38-year-old woman who presented with bilateral CAPNON, diagnosed 8 years apart. While there are approximately 46 reported in the current literature of cerebral and spinal fibro-osseous lesions, this is the first report of separate lesions.

Indirect Bypass With Pericranial Transposition for Moyamoya Syndrome in an Infant.

Moyamoya syndrome (MMS) is a progressive disease that can result in debilitating strokes. Surgical revascularization is the mainstay of treatment. Selection of the proper bypass technique depends on the vascular anatomy and location of the hypoperfused cerebral territory. We describe here a case of successful indirect bypass utilizing a pericranial flap as well as dural inversion. A seven-month-old female was transferred from an outside facility to our institution for further evaluation and surgical treatment of MMS. She presented with bilateral brain infarcts worse on the left, with right-sided body weakness. After medical stabilization and hyperhydration, she was taken to the operating room for a left-sided indirect bypass. The superficial temporal artery (STA) was traced utilizing doppler but was determined to be too diminutive for transposition, so the decision was made to proceed with encephalo-duro-pericranio-synangiosis (EDPS). A pericranial graft was successfully affixed to the cortical surface in the hypoperfused middle cerebral artery (MCA) territory, and the dura was inverted. Postoperatively, the patient developed a pseudomeningocele, so a revision surgery was performed. She was discharged shortly after this and returned for encephalo-duro-arterio-synangiosis (EDAS) of the contralateral side. She followed up three months after her initial bypass surgery at age 10 months and was crawling without any focal deficits. She was lost to follow-up thereafter. EDPS is a safe technique for infants with MMS whose STA is too diminutive to be used for bypass surgery. This may be an effective method for indirect bypass in these patients.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Patients With Chiari Malformation: Surgical Interventions.

BACKGROUND: Chiari malformation type I (CIM) diagnoses have increased in recent years. Controversy regarding the best operative management prompted a review of the literature to offer guidance on surgical interventions. OBJECTIVE: To assess the literature to determine (1) whether posterior fossa decompression or posterior fossa decompression with duraplasty is more effective in preoperative symptom resolution; (2) whether there is benefit from cerebellar tonsillar resection/reduction; (3) the role of intraoperative neuromonitoring; (4) in patients with a syrinx, how long should a syrinx be observed for improvement before additional surgery is performed; and 5) what is the optimal duration of follow-up care after preoperative symptom resolution. METHODS: A systematic review was performed using the National Library of Medicine/PubMed and Embase databases for studies on CIM in children and adults. The most appropriate surgical interventions, the use of neuromonitoring, and clinical improvement during follow-up were reviewed for studies published between 1946 and January 23, 2021. RESULTS: A total of 80 studies met inclusion criteria. Posterior fossa decompression with or without duraplasty or cerebellar tonsil reduction all appeared to show some benefit for symptom relief and syrinx reduction. There was insufficient evidence to determine whether duraplasty or cerebellar tonsil reduction was needed for specific patient groups. There was no strong correlation between symptom relief and syringomyelia resolution. Many surgeons follow patients for 6-12 months before considering reoperation for persistent syringomyelia. No benefit or harm was seen with the use of neuromonitoring. CONCLUSION: This evidence-based clinical guidelines for the treatment of CIM provide 1 Class II and 4 Class III recommendations. In patients with CIM with or without syringomyelia, treatment options include bone decompression with or without duraplasty or cerebellar tonsil reduction. Improved syrinx resolution may potentially be seen with dural patch grafting. Symptom resolution and syrinx resolution did not correlate directly. Reoperation for a persistent syrinx was potentially beneficial if the syrinx had not improved 6 to 12 months after the initial operation. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/3-surgical-interventions .

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Patients With Chiari Malformation: Diagnosis.

BACKGROUND: Chiari I malformation (CIM) is characterized by descent of the cerebellar tonsils through the foramen magnum, potentially causing symptoms from compression or obstruction of the flow of cerebrospinal fluid. Diagnosis and treatment of CIM is varied, and guidelines produced through systematic review may be helpful for clinicians. OBJECTIVE: To perform a systematic review of the medical literature to answer specific questions on the diagnosis and treatment of CIM. METHODS: PubMed and Embase were queried between 1946 and January 23, 2021, using the search strategies provided in Appendix I of the full guidelines. RESULTS: The literature search yielded 567 abstracts, of which 151 were selected for full-text review, 109 were then rejected for not meeting the inclusion criteria or for being off-topic, and 42 were included in this systematic review. CONCLUSION: Three Grade C recommendations were made based on Level III evidence. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/1-imaging .

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Patients With Chiari Malformation: Symptoms.

BACKGROUND: Chiari I malformation (CIM) is characterized by descent of the cerebellar tonsils through the foramen magnum, potentially causing symptoms from compression or obstruction of the flow of cerebrospinal fluid. Diagnosis and treatment of CIM is varied, and guidelines produced through systematic review may be helpful for clinicians. OBJECTIVE: To perform a systematic review of the medical literature to answer specific questions on the diagnosis and treatment of CIM. METHODS: PubMed and Embase were queried between 1946 and January 23, 2021, using the search strategies provided in Appendix I of the full guidelines. RESULTS: The literature search yielded 430 abstracts, of which 79 were selected for full-text review, 44 were then rejected for not meeting the inclusion criteria or for being off-topic, and 35 were included in this systematic review. CONCLUSION: Four Grade C recommendations were made based on Class III evidence, and 1 question had insufficient evidence. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/2-symptoms .

Real-Time Peer-to-Peer Observation and Feedback Lead to Improvement in Oral Presentation Skills.

Background Oral case presentation is a vital skill in many fields, particularly in medicine, and is taught early on in medical schools. However, there is a diminished focus on the development of this skill during the clinical years. In this study, we investigated whether the implementation of a formal teaching strategy during the internal medicine clerkship rotation can lead to an improvement in oral presentation skills. Methodology Students received an introductory PowerPoint lecture and saw brief video presentations summarizing the key components of a successful oral presentation. Subsequently, students were asked to evaluate their peers while they presented during morning rounds using a standardized feedback form in the first and the second half of their rotation. Using the information gained from the feedback form, students provided verbal feedback on the quality of oral presentations to their peers. Results A total of 64 students participated in this curriculum at a university-affiliated teaching hospital, and a total of 409 evaluations were completed. The average total score during the first and the second rotation period was 93.0% (standard deviation, SD = 9.8) and 96.9% (SD = 7.1), respectively. Improvement in the total score of 3.7% points was seen in the entire cohort, with an average improvement of 64% (or 1.64 times) in the probability of obtaining a full score during the second rotation. Conclusions Our data show improvement in scores between collection blocks using an educational strategy. This study emphasizes the fact that peer-to-peer evaluations helped in the refinement of oral presentation skills.

Neurovascular Syndromes.

Patients with cerebrovascular syndromes are at risk for additional concerns associated with their syndrome. A wide variety of syndromes are associated with cerebrovascular diseases. Multidisciplinary care is helpful to ensure comprehensive evaluation and management. Precise diagnosis and appreciation for the underlying syndrome is critical for effective cerebrovascular and broader care. This text focuses on these conditions with a focus on underlying pathophysiology and associated genetics, presentation, diagnosis, and management of each disease.

Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction.

Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain's vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.

Lumbar Ganglioneuroma Presenting With Scoliosis.

Ganglioneuromas are rare, benign tumors arising from the sympathetic nervous system. The presentation of the tumor is variable and may be associated with scoliosis. Few reports of ganglioneuroma associated with scoliosis- exist and most involve the thoracic spine. Here, we present a 13-year-old female with scoliosis who was found to have a lumbar ganglioneuroma. The patient was treated with a subtotal resection and lumbar spinal fusion to correct her scoliosis in a single-stage operation. The patient's symptoms and scoliosis markedly improved following treatment without any complications. Additionally, we conducted an up-to-date literature review of ganglioneuromas associated with scoliosis that have been published in the last 20 years. We discuss variations in clinical presentation and surgical approach.

Thirty-Day Hospital Readmissions: A Predictor of Higher All-cause Mortality for Up to Two Years.

Introduction Readmission within 30 days is used as a standard quality metric for hospitalized patients. We hypothesized that patients who get readmitted within 30 days may have higher short- and long-term mortality. Material and Methods Using administrative data, we retrospectively analyzed 2,353 patients admitted to inpatient medicine service over a period of one year. The patients were matched for diagnostic group (DRG) and severity index (SI) using nearest propensity scores in a 2:1 ratio between non-readmissions (NRA) to readmissions (RA) patients. Results There was no statistically significant difference in the groups between age, sex, length of stay (LOS), race, and ethnicity. The hazard model yielded a hazard ratio (HR) of 2.06 for 30-day readmissions (95% CI of 1.55, 2.74; p=<0.001). The survival probability at 6, 12, 18, and 24 months was consistently greater for NRA patients.  Conclusions Thirty-day readmissions are an independent risk factor for all-cause mortality which persists for at least two years independent of DRG and SI.

Readmissions on Teaching Versus Non-Teaching Services: Are They Any Different?

Introduction There is a paucity of comparative data on readmissions between teaching services (TS) and nonteaching services (NTS). Therefore, we designed this study to determine if there are any differences in readmissions between the two services. Materials and methods A unique cohort of 384 readmissions during one year was retrospectively examined at Hunter Holmes McGuire Veterans Medical Center. The data on patient demographics, baseline characteristics, comorbid illnesses, length of stay (LOS), and reasons for readmission within 30 days were extracted. Results There were no differences in readmission rates (8.2% vs. 10.2%; P = .135), LOS during index admission (4.2 ± 4.8 vs. 4.1 ± 3.5; P = .712), and age-adjusted Charlson Comorbid Index Score (6.1 ± 3.0 vs. 6.8 ± 2.8; P = .037) between the TS and NTS groups. However, the reasons for readmissions between the two groups were statistically significantly different (P < .01). Specifically, these differences were found between system issues and new diagnoses. The NTS showed higher rates of readmissions secondary to new diagnoses and systems issues, whereas the TS showed higher rates of secondary to clinician issues and disease progression. Conclusions We have a new understanding of the difference in reasons for readmissions between TS and NTS; it possibly results from the different structures of the two teams, which may help us address readmissions in a different light to improve overall readmission rate.

Identification of an association between Robinow syndrome and moyamoya.

INTRODUCTION: Our group, along with others, has previously reported associations between moyamoya syndrome and a number of genetic disorders, including Down syndrome, Seckel dwarfism, sickle cell disease, and neurofibromatosis type I. Here we present the first reported case of a patient with the concomitant diagnosis of moyamoya and Robinow syndrome - a rare genetic disorder characterized by fetal-like faces, mesomelic shortening of the forearms, and developmental delay. The clinical, radiographic, and surgical findings are described, as well as the importance of this association. METHODS: Case report. RESULTS: A 13-year-old girl with Robinow syndrome presented with multiple transient ischemic attacks consisting of speech arrest and generalized weakness. Evaluation revealed probable bilateral moyamoya syndrome. Initially, she was treated conservatively due to the rarity of her symptoms and relatively unremarkable angiographic findings. However, she ultimately had progression of her disease both clinically and radiographically, leading to surgical management. She underwent staged bilateral pial synangiosis without complication and has done well subsequently. CONCLUSION: The potential difficulty of detecting symptoms related to cerebral ischemia in the Robinow's population - where cognitive impairment may obscure initial neurologic symptoms - can result in delayed diagnosis and treatment. Given the excellent outcomes of moyamoya patients when treated prior to the development of fixed neurologic deficits, case reports such as this and identifying syndromic associations serve to highlight conditions that may result in improved patient outcomes through earlier diagnosis and treatment. The clinical and radiographic features of moyamoya syndrome associated with Robinow syndrome seem comparable to those of primary moyamoya disease. The presence of moyamoya syndrome should be considered in the evaluation of patients with Robinow syndrome who present with transient ischemic attack-like symptoms.

Venous Manometry as an Adjunct for Diagnosis and Multimodal Management of Intracranial Hypertension due to Meningioma Compressing Sigmoid Sinus.

Intracranial venous hypertension is a rare presentation of meningiomas in the transverse-sigmoid sinus region. We describe a case of a young patient presenting with intracranial hypertension due to a meningioma causing compression of the dominant sigmoid sinus. We were able to document the cerebral venous pressure gradient across the lesion confirming our hypothesis that compression of the sigmoid sinus from the meningioma was the cause of intracranial hypertension. The patient is a 17-year-old male who presented with intracranial hypertension due to meningioma at the right dominant sigmoid sinus, which was treated by a Simpson grade IV surgical resection followed by stereotactic radiosurgery. Following treatment, his papilledema resolved and he remains symptom-free at 18 months. In conclusion, venous manometry is a useful adjunct to diagnose intracranial hypertension in non-idiopathic causes of intracranial hypertension. A multimodal management approach of intracranial hypertension due to outflow obstruction from the dominant sinus led to an excellent recovery on follow up.

Pregnancy after direct cerebral bypass for moyamoya disease.

OBJECTIVE: Moyamoya disease (MMD) disproportionately affects young to middle-aged women. The main treatment for this challenging disease is cerebral bypass surgery. Vascular neurosurgeons often need to counsel women regarding pregnancy following bypass for MMD, but there is a paucity of data. The authors set out to examine neurological and obstetric outcomes in an extensive cohort of MMD patients who had pregnancies following cerebral revascularization at the Stanford Medical Center. METHODS: The authors identified all patients at their institution who underwent cerebral bypass for MMD from 1990 through 2018 and who later became pregnant. Some of these patients also had pregnancies prior to undergoing bypass surgery, and the authors examined these pregnancies as well. They performed a chart review and brief telephone survey to identify obstetric complications, transient ischemic attacks (TIAs), and strokes. Neurological and obstetric outcomes were compared to published rates. They also compared pre- and post-bypass pregnancy complication rates using logistic regression techniques. RESULTS: There were 71 pregnancies among 56 women whose mean age was 30.5 years. Among 59 post-bypass pregnancies, there were 5 (8%) perinatal TIAs. There were no MRI-confirmed strokes or strokes with residual deficits. Among 12 pre-bypass pregnancies, there were 3 (25%) TIAs and 2 (17%) MRI-confirmed strokes. There were no hemorrhagic complications in either group. In the generalized estimating equations analysis, performing cerebral revascularization prior to pregnancy versus after pregnancy was associated with lower odds of perinatal stroke or TIA (OR 0.15, p = 0.0061). Nine pregnancies (13%) were complicated by preeclampsia, and there was one (1%) instance of eclampsia. The overall rate of cesarean delivery was 39%. There were 2 miscarriages, both occurring in the first trimester. There were no maternal deaths. CONCLUSIONS: The authors present neurological and obstetric outcomes data in a large cohort of MMD patients. These data indicate that post-bypass pregnancy is accompanied by low complication rates. There were no ischemic or hemorrhagic strokes among post-bypass pregnant MMD patients. The rate of obstetric complications was low overall. The authors recommend close collaboration between the vascular neurosurgeon and the obstetrician regarding medical management, including blood pressure goals and continuation of low-dose aspirin.

Attitudes towards genetic diagnosis in Pakistan: a survey of medical and legal communities and parents of thalassemic children.

OBJECTIVES: It was the aim of this study to assess the attitudes of doctors, medical students, lawyers, parliament members and parents of thalassemic children towards genetic diagnosis in Pakistan. STUDY DESIGN: A cross-sectional descriptive survey was conducted among representative samples. RESULTS: Five hundred and seventy doctors, 49 lawyers, 178 medical students, 89 parents of thalassemic children and 16 members of parliament (MPs) were included in the survey. The groups showed considerable difference in their attitudes towards different aspects of the issue. A large proportion (88.5%) agreed to the idea of genetic diagnostic screening, especially the parents of thalassemic patients. Premarital carrier screening was favored by 77% of the respondents. Prenatal screening was most favored by the parents of thalassemic children (94.4%). Likewise, a majority of parents of thalassemic children were in favor of abortion in case of an affected fetus. Genetic self-screening was also favored most by the parents of thalassemic patients (78.2%). Only 24% of the doctors favored making genetic screening mandatory, whereas 63% of the parents agreed to the idea. CONCLUSION: Attitudes regarding genetic diagnosis are markedly different among various societal groups in Pakistan. The parents of the affected children strongly favor genetic screening as does the medical community, though not as strongly as the parents. The legislative groups, particularly the MPs, are reserved in their support. Genetic diagnosis can help decrease the disease burden in the future. However, it raises a number of ethical issues, which need to be addressed. It is important to educate the population about potential benefits as well as ethical dilemmas involved so that the general public is able to make the right decisions for themselves and their families.

Corrigendum to "Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms".

[This corrects the article DOI: 10.1155/2016/8781725.].

Blast Scaling Parameters: Transitioning from Lung to Skull Base Metrics.

Neurotrauma from blast exposure is one of the single most characteristic injuries of modern warfare. Understanding blast traumatic brain injury is critical for developing new treatment options for warfighters and civilians exposed to improvised explosive devices. Unfortunately, the pre-clinical models that are widely utilized to investigate blast exposure are based on archaic lung based parameters developed in the early 20th century. Improvised explosive devices produce a different type of injury paradigm than the typical mortar explosion. Protective equipment for the chest cavity has also improved over the past 100 years. In order to improve treatments, it is imperative to develop models that are based more on skull-based parameters. In this mini-review, we discuss the important anatomical and biochemical features necessary to develop a skull-based model.