Primary epidural sporadic Burkitt lymphoma in a 3-year-old: Case report and literature review.

Background: Burkitt lymphoma (BL) is a common tumor of childhood that usually arises in the abdomen or pelvis in its sporadic form. In a minority of cases, BL can present with CNS involvement, usually as a secondary site. Rarely, BL can arise primarily in the epidural space and present with back pain, or less commonly, acute myelopathy. This presentation is a surgical emergency and requires vigilant management. Case Description: We describe a case of pediatric BL arising primarily within the epidural space and presenting with progressive difficulty walking in a 3-year-old boy. Progression to complete inability to walk, absent lower extremity deep tendon reflexes, and new urinary incontinence prompted MRI of the spine, which showed a lesion extending from T5 to T10 and wrapping around the anterior and posterior portions of the spine with evidence of spinal cord compression. The patient underwent decompressive laminectomies from T5 to T10 and partial debulking of the posterior portions of the tumor. Microscopic examination showed a prominent "starry sky" pattern with abundant mitotic figures. Immunohistochemistry confirmed the diagnosis of BL. The patient is 10 months post-op and continues to undergo chemotherapy with partial neurologic improvement. He was free of recurrence 10 months post-operative. Conclusion: This appears to be the youngest described patient presenting with acute myelopathy in primary paraspinal BL. Management should include surgical decompression of the spinal cord followed by one of the various described chemotherapeutic regimens. Preoperative staging and neurologic function correlate with prognosis.

Cognitive task-related oscillations in human internal globus pallidus and subthalamic nucleus.

Recently it has been acknowledged that the basal ganglia nuclei play a major role in cognitive control; however, the contribution by their network remains unclear. Previous studies have demonstrated the role of the subthalamic nucleus (STN) in cognitive processing and suggested that its connections to cortical and other associated regions regulate response inhibition during conflict conditions. By contrast, the role of the internal globus pallidus (GPi) as the output nucleus before the thalamic relay has not yet been investigated during cognitive processing. We recorded local field potentials (LFPs) from externalized deep brain stimulation (DBS) electrodes implanted bilaterally in the GPi (n = 9 participants with dystonia) and STN (n = 8 participants with Parkinson's disease (PD)) during a primed flanker task. Both dystonia (GPi group) and PD participants (STN group) responded faster to the congruent trials than the incongruent trials. Overall, the dystonic GPi group was significantly faster than the PD STN group. LFPs showed elevated cue-triggered theta (3-7 Hz) power in GPi and STN groups in a similar way. Response-triggered LFP beta power (13-25 Hz) was significantly increased in the GPi group compared to the STN group. Results demonstrate that GPi activity appears to be critical in the cognitive processing of action selection and response during the presence of conflict tasks similar to the STN group.

Hemorrhagic spinal melanotic schwannoma presenting as acute chest pain: A case report and literature review.

BACKGROUND: Melanotic schwannoma (MS) is a rare variant of peripheral nerve sheath tumor. MS commonly arises along the spinal nerve sheath. Patients most often experience pain along the dermatome of the affected nerve root. Symptoms development is usually insidious. About half of MS cases are associated with Carney complex, a multi-neoplastic disorder. The remaining cases arise spontaneously. About 10-44% of these tumors undergo malignant transformation. CASE DESCRIPTION: We describe a case of hemorrhagic MS presenting as acute chest pain mimicking myocardial infarction, a presentation which has not yet been described in the literature. Neurologic examination did not reveal any abnormalities. Myocardial infarction was ruled out in the ER, and a chest CT angiogram was ordered for evaluation of PE or aortic dissection which revealed an intradural extramedullary dumbbell-shaped mass extending through the left vertebral foramen at the level of T8. MRI revealed a heterogenous mass that was hyperintense with T2 and hypointense with T1-weighted imaging. The patient underwent an open laminectomy of the left T8 and T9 vertebrae and gross total resection (GTR) of a hemorrhagic black tumor. Microscopic examination showed fascicles and nests of plump spindle cells with variable intracellular melanin. Immunohistochemistry showed the cells to be positive for S100, SOX10, HMB-45, and MART-1, confirming diagnosis of MS. Two months after the operation, the patient was doing well and is free of recurrence. CONCLUSION: GTR is considered the optimal treatment for MS; radiotherapy and chemotherapy may be considered but have not been shown to improve patient outcomes.

The Residency Match in South Dakota: A National Comparison of Specialty and Geographic Trends.

BACKGROUND: Current estimates suggest progressively increasing need for rural family medicine and primary care providers in the near future. Predominantly rural states such as South Dakota have even greater difficulty in attracting these providers. Since its founding, the Sanford School of Medicine (SSOM) at the University of South Dakota has designed its curriculum to encourage students to choose these specialties and practice within the state upon completing residency. The objective of this paper was to evaluate trends in specialty choice and geographic location of residency programs for SSOM graduates compared with national means. METHODS: A retrospective observational analysis of residency match data including specialty and geographic location of the program was performed for matched seniors of SSOM from the years 2000-2020 and compared to national data over the same period. RESULTS: The proportions of students matching with primary care, surgical, or medical specialties at SSOM was not significantly different from national means. Proportionally, SSOM had almost twice the national average of students matching into family medicine (17.5 percent vs 9.0 percent). A significantly greater proportion of SSOM graduates matched into general surgery (8.1 percent vs 6.0 percent). SSOM students were significantly more likely (71.5 percent) than national (63.0 percent) and Midwest (58 percent) averages to match within their home region. CONCLUSIONS: SSOM's curriculum has led to a greater proportion of graduates matching with family medicine programs and at the national average for primary care overall. SSOM students are also significantly more likely than the national average to match within the same region of their medical school.

Pineal Cyst Apoplexy in an 8-Year-Old Girl: Case Report and Literature Review.

BACKGROUND: Pineal cysts are common, typically asymptomatic, and are usually found incidentally in adults. In rare cases, pineal cyst apoplexy occurs as a result of an acute cystic hemorrhage. This situation can result in acute onset of severe headaches, acute obstructive hydrocephalus, mass effect on the midbrain, and even death. Pineal apoplexy is most common in women of reproductive age, whereas pediatric cases continue to be less prevalent. Pineal cyst apoplexy remains a rare entity with ≥30 cases presented in the literature to date. CASE DESCRIPTION: We present the youngest case in the literature (an 8-year-old girl with a pineal cyst that resulted in apoplexy), her diagnostic workup, management, and follow-up. We supplement our case study with a literature review of pineal cyst apoplexy. CONCLUSIONS: Pineal cyst apoplexy remains a rare clinical event in the pediatric population. Our case details the diagnosis and management of an 8-year-old girl with pineal cyst apoplexy. We also discuss our findings from our literature search for all reported cases of pineal cyst apoplexy.

In situ clearance of a proximal shunt malfunction in a child with hydrocephalus post cerebral arteriovenous malformation rupture noted intraoperatively.

BACKGROUND: Hydrocephalus shunt malfunctions remain treated with surgical intervention only. Despite efforts at identifying or preventing CSF shunt obstruction, no evidence currently exists to restore CSF flow following proximal occlusion, non-invasively. CASE DESCRIPTION: We present direct intraoperative evidence in the case of a 5-year-old male who developed hydrocephalus subsequent to hemorrhagic presentation post cerebral arteriovenous malformation rupture. After weeks of externalized CSF diversion for clearance of CSF red blood cells, he was taken to the operating room for removal of the external ventricular drain and placement of a ventriculoperitoneal shunt for hydrocephalus. At conclusion of placing his ventriculoperitoneal shunt with ReFlow flusher assist device, his shunt valve reservoir was noted to not refill. Following manual depression of the ReFlow flusher, we identified clearance of debris from the obstructed ventricular catheter allowing reestablished CSF flow through the shunt system under live intraoperative ultrasonography. Subsequently, there was return of brisk refill to the shunt valve reservoir. CONCLUSION: Observations here demonstrate a potentially useful technical strategy toward clearance of proximal shunt obstructions, in situ.

Characterization of a novel rat model of X-linked hydrocephalus by CRISPR-mediated mutation in L1cam.

OBJECTIVE: Emergence of CRISPR/Cas9 genome editing provides a robust method for gene targeting in a variety of cell types, including fertilized rat embryos. The authors used this method to generate a transgenic rat L1cam knockout model of X-linked hydrocephalus (XLH) with human genetic etiology. The object of this study was to use diffusion tensor imaging (DTI) in studying perivascular white matter tract injury in the rat model and to characterize its pathological definition in histology. METHODS: Two guide RNAs designed to disrupt exon 4 of the L1cam gene on the X chromosome were injected into Sprague-Dawley rat embryos. Following embryo transfer into pseudopregnant females, rats were born and their DNA was sequenced for evidence of L1cam mutation. The mutant and control wild-type rats were monitored for growth and hydrocephalus phenotypes. Their macro- and microbrain structures were studied with T2-weighted MRI, DTI, immunohistochemistry, and transmission electron microscopy (TEM). RESULTS: The authors successfully obtained 2 independent L1cam knockout alleles and 1 missense mutant allele. Hemizygous male mutants from all 3 alleles developed hydrocephalus and delayed development. Significant reductions in fractional anisotropy and axial diffusivity were observed in the corpus callosum, external capsule, and internal capsule at 3 months of age. The mutant rats did not show reactive gliosis by then but exhibited hypomyelination and increased extracellular fluid in the corpus callosum. CONCLUSIONS: The CRISPR/Cas9-mediated genome editing system can be harnessed to efficiently disrupt the L1cam gene in rats for creation of a larger XLH animal model than previously available. This study provides evidence that the early pathology of the periventricular white matter tracts in hydrocephalus can be detected in DTI. Furthermore, TEM-based morphometric analysis of the corpus callosum elucidates the underlying cytopathological changes accompanying hydrocephalus-derived variations in DTI. The CRISPR/Cas9 system offers opportunities to explore novel surgical and imaging techniques on larger mammalian models.

Management of autonomic dysreflexia associated with Charcot spinal arthropathy in a patient with complete spinal cord injury: Case report and review of the literature.

BACKGROUND: Charcot spinal arthropathy (CSA) clearly represents a challenge in long-term spinal cord injury patients, one that can have extremely uncomfortable and potentially lethal outcomes if not managed properly. CASE DESCRIPTION: A 66-year-old man with a history of complete C7 quadriplegia presented with new-onset autonomic dysreflexia that resulted from Charcot spinal arthropathy (CSA). Pathologic instability, in the atypical site of the mid-thoracic spine, spanning from the T8-T9 vertebral levels was appreciated on physical exam as an audible, palpable, and visible dynamic kyphosis; kyphosis was later confirmed on neuroimaging. Based on the CSA severity and sequelae, the patient underwent bilateral decompression laminectomy with lateral extracavitary arthrodesis and posterior instrumentation. Symptoms dramatically improved and at 1-year follow-up, dynamic thoracic kyphosis and most symptoms of autonomic dysreflexia had resolved. CONCLUSIONS: Based on our case and published reports, vigilant imaging and thorough physical examination in long-standing spinal cord injury could help early diagnosis and treatment of CSA, theoretically preventing development of cord atrophy and subsequent long-term sequelae. Surgical correction rather than bracing may be recommended in patients who have complete injury at or above T6 in patients with symptoms of autonomic dysreflexia associated with CSA confirmed on neuroimaging.

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 (Ccdc39) is responsible for early postnatal hydrocephalus in the progressive hydrocephalus (prh) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development.

Application of emerging technologies to improve access to ischemic stroke care.

During the past 20 years, the traditional supportive treatment for stroke has been radically transformed by advances in catheter technologies and a cohort of prominent randomized controlled trials that unequivocally demonstrated significant improvement in stroke outcomes with timely endovascular intervention. However, substantial limitations to treatment remain, among the most important being timely access to care. Nonetheless, stroke care has continued its evolution by incorporating technological advances from various fields that can further reduce patients' morbidity and mortality. In this paper the authors discuss the importance of emerging technologies-mobile stroke treatment units, telemedicine, and robotically assisted angiography-as future tools for expanding access to the diagnosis and treatment of acute ischemic stroke.

Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy.

Vascular pathologies of the spinal cord are rare and often overlooked. This article presents clinical and imaging approaches to the diagnosis and management of spinal vascular conditions most commonly encountered in clinical practice. Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical classification schemes, clinical presentations, imaging findings, and treatment modalities are considered. Recent advances in genetic and syndromic vascular pathologies of the spinal cord are also discussed. Clinically relevant spinal vascular anatomy is reviewed in detail.

Aneurysm growth and de novo aneurysms during aneurysm surveillance.

OBJECTIVE Many low-risk unruptured intracranial aneurysms (UIAs) are followed for growth with surveillance imaging. Growth of UIAs likely increases the risk of rupture. The incidence and risk factors of UIA growth or de novo aneurysm formation require further research. The authors retrospectively identify risk factors and annual risk for UIA growth or de novo aneurysm formation in an aneurysm surveillance protocol. METHODS Over an 11.5-year period, the authors recommended surveillance imaging to 192 patients with 234 UIAs. The incidence of UIA growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for UIA growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed. RESULTS During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth and 4.3% of aneurysms had grown. Four de novo aneurysms formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth (UIA < 5 mm = 1.6% vs UIA ≥ 5 mm = 8.7%, p = 0.002). Patients with growing UIAs were more likely to also have de novo aneurysms (p = 0.01). Patient compliance with this protocol was 65%, with younger age predictive of better compliance (p = 0.01). CONCLUSIONS Observation of low-risk UIAs with surveillance imaging can be implemented safely with good adherence. Aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted.

MRSA peritonitis secondary to perforation of sigmoid diverticulitis.

The occurrence of methicillin-resistant Staphylococcus aureus (MRSA) is well documented, but the pathology is usually associated with post surgical infections or long-term peritoneal dialysis. We report the case of a 50-year-old Caucasian man who presented with a one week history of left lower quadrant abdominal pain, poor appetite and nausea due to MRSA peritonitis secondary to perforated sigmoid diverticulitis. Despite a thorough search of the medical literature, we could not find that this problem has been previously described. We report this case to demonstrate the robust nature of MRSA, which has generally not been considered to be a normal colonizing bacterium of the sigmoid colon.

Chronic amphetamine treatment enhances corticotropin-releasing factor-induced serotonin release in the amygdala.

Amphetamine use is associated with dysphoric states, including heightened anxiety, that emerge within 24h of withdrawal from the drug. Corticotropin-releasing factor increases serotonin release in the central nucleus of the amygdala, and this neurochemical circuitry may play a role in mediating fear and anxiety states. We have previously shown that chronic amphetamine treatment increases corticotropin-releasing factor receptor type-2 levels in the serotonergic dorsal raphe nucleus of the rat. Therefore, we hypothesized that chronic amphetamine treatment would enhance the amygdalar serotonergic response to corticotropin-releasing factor infused into the dorsal raphe nucleus. Male rats were injected once-daily with d-amphetamine (2.5mg/kg i.p., or saline) for two weeks. Serotonin release within the central nucleus of the amygdala in response to intra-raphe infusion of corticotropin-releasing factor (100 ng) was measured 24h after the last treatment in urethane-anesthetized (1.8 mg/kg, i.p.) rats using in vivo microdialysis. Rats pretreated with amphetamine showed significantly enhanced serotonin release in the central nucleus of the amygdala in response to corticotropin-releasing factor infusion when compared to saline pretreated rats. Furthermore, this enhanced response was blocked by the corticotropin-releasing factor type-2 receptor antagonist antisauvagine-30 (2 microg) infused into the dorsal raphe nucleus. These results suggest increased sensitivity to corticotropin-releasing factor as mediated by type-2 receptors following chronic amphetamine treatment, which may underlie dysphoric states observed during amphetamine withdrawal.

Increased anxiety-like behavior of rats during amphetamine withdrawal is reversed by CRF2 receptor antagonism.

Withdrawal from psychostimulants increases anxiety states, and amphetamine-treated rats show increased CRF(2) receptors in the serotonergic cell body region, the dorsal raphe nucleus (dRN). In the current study, amphetamine (2.5 mg/kg, i.p., 14 days) pre-treated rats spent less time in open arms of the elevated plus maze compared saline pre-treated rats at both 24h or 2 weeks of withdrawal, and CRF(2) receptor antagonism (ASV-30; 2 microg/0.5 microl) within the dRN reversed the effects of amphetamine withdrawal on anxiety-like behavior. Overall, results suggest that CRF(2) receptor antagonism may be a novel pharmacological target for anxiety states during drug withdrawal.

Corticotropin-releasing factor receptor antagonism within the dorsal raphe nucleus reduces social anxiety-like behavior after early-life social isolation.

Social isolation of rats during the early part of development increases social anxiety-like behavior in adulthood. Furthermore, early-life social isolation increases the levels of corticotropin-releasing factor (CRF) receptors in the serotonergic dorsal raphe nucleus (dRN) of adult rats. Interactions between serotonin and CRF systems are thought to mediate anxiety behavior. Therefore, we investigated the effects of CRF receptor antagonism within the dRN on social anxiety-like behavior after early-life social isolation. Male rats were reared in isolation or in groups from weaning until midadolescence, and rehoused in groups and allowed to develop into adulthood. Adult rats underwent surgery to implant a drug cannula into the dRN. After recovery from surgery and acclimation to the testing arena, rats were infused with vehicle or the CRF receptor antagonist d-Phe-CRF((12-41)) (50 or 500 ng) into the dRN before a social interaction test. Isolation-reared rats pretreated with vehicle exhibited increased social anxiety-like behavior compared with rats reared in groups. Pretreatment of the dRN with d-Phe-CRF((12-41)) significantly reduced social anxiety-like behaviors exhibited by isolation-reared rats. Overall, this study shows that early-life social stress results in heightened social anxiety-like behavior, which is reversed by CRF antagonism within the dRN. These data suggest that CRF receptor antagonists could provide a potential treatment of stress-related social anxiety.

Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity.

Interactions between central corticotropin-releasing factor (CRF) and serotonergic systems are believed to be important for mediating fear and anxiety behaviors. Recently we demonstrated that infusions of CRF into the rat dorsal raphe nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. The current studies were designed to study the CRF receptor mechanisms and pathways involved in this serotonergic response. Infusions of CRF (0.5 microg/0.5 microL) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 microL) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25-50 ng/0.5 microL) or antisauvagine-30 (2 microg/0.5 microL), respectively. Medial prefrontal cortex serotonin levels were measured using in-vivo microdialysis and high-performance liquid chromatography with electrochemical detection. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal raphe nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central nucleus of the amygdala, a source of CRF afferents to the dorsal raphe nucleus. Activation of the central nucleus increased medial prefrontal cortex serotonin release. This response was blocked by CRF receptor type 2 antagonism in the dorsal raphe. Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the raphe nuclei.