In Utero Restoration of Hindbrain Herniation in Fetal Myelomeningocele as Part of Prenatal Regenerative Therapy Program at Mayo Clinic.

OBJECTIVE: To assess our initial experience with prenatal restoration of hindbrain herniation following in utero repair of myelomeningocele (MMC). PATIENTS AND METHODS: Three consecutive patients with prenatally diagnosed MMC (between January 1, 2018 and September 30, 2018) were managed with open in utero surgery. As per institutional review board approval and following a protocol designed at the Mayo Clinic Maternal & Fetal Center, fetal intervention was offered between 19 0/7 and 25 6/7 weeks of gestation. Prenatal improvement of hindbrain herniation was the declared restorative end point. Obstetrical and perinatal outcomes were also assessed. RESULTS: Diagnosis of MMC was confirmed upon referral between 20 and 21 weeks' gestation by using fetal ultrasound and magnetic resonance imaging. In all cases reported here, the spinal defect was lumbosacral with evidence of hindbrain herniation. Open in utero MMC repair was performed between 24 and 25 weeks' gestation with no notable perioperative complications. Postprocedure fetal magnetic resonance imaging performed 6 weeks after in utero repair documented improvement of hindbrain herniation. Deliveries were at 37 weeks by cesarean section without complications. Most recent postnatal follow-ups were unremarkable at both 11 months (baby 1) and 3 months of age (baby 2), with mild ventriculomegaly. Antenatal and postnatal follow-up of baby 3 at 1 month of age was also unremarkable. CONCLUSION: Our study highlights the prenatal restoration of hindbrain herniation following in utero MMC repair in all cases presented here as an example of a prenatal regenerative therapy program in our institution.

Validating the management paradigm for pediatric spinal aneurysmal bone cysts to optimize long-term outcomes: an institutional experience.

BACKGROUND: The optimal clinical management and outcomes of rare pediatric spinal aneurysmal bone cysts (spABC) is largely anecdotal. Current practice is based on bigger adult series, although given the disparities in spine growth of adults versus children, what impact this difference may have on long-term outcomes has yet to be substantiated. Correspondingly, the aim of this study was to describe the clinical course of all pediatric spABC cases managed at our institution to better understand this. METHODS: A retrospective cohort study of all pediatric spABC cases presenting to our institution between 1993 and 2017 was performed using a predetermined set of selection criteria. Primary outcomes of interest were treatment modalities and their outcomes, recurrence status, and functional status. RESULTS: A total of 24 pediatric spABC cases satisfied all criteria. Median age of diagnosis was 13.5 years, with 15 females and 9 males. Radicular pain was the presenting symptom in 21 (88%) cases. Diagnostic biopsy was pursued in 9 (38%) cases, pre-operative embolization in 8 (33%) cases, surgical intervention in 23 (96%) cases, and sclerotherapy in 2 (8%) cases. In terms of surgery, there were no intraoperative complications, and gross total resection (GTR) was achieved in 14 of the 23 (61%) cases. Overall, there were 5 (21%) cases which experienced recurrence by a median time of 8 months after initial surgery, all of which had initial subtotal resection. Median follow-up was 5 years, by which all patients demonstrated excellent functional status. CONCLUSIONS: There are a number of feasible therapeutic modalities and combinations that can be utilized to maximize control of pediatric spABCs and optimize long-term function similar to that of adults, irrespective of developing versus developed spines. The incidence of recurrence is not negligible, and therefore, rigorous long-term surveillance is highly encouraged, particularly within the first post-operative year following mono-modal non-GTR treatment.

Progressive hydrocephalus despite early complete reversal of hindbrain herniation after prenatal open myelomeningocele repair.

OBJECTIVE: Open prenatal myelomeningocele (MMC) repair is typically associated with reversal of in utero hindbrain herniation (HBH) and has been posited to be associated with a reduction in both postoperative prenatal and immediate postnatal hydrocephalus (HCP) risks. However, the long-term postnatal risk of HCP following HBH reversal in these cases has not been well defined. The authors describe the results of a long-term HCP surveillance in a cohort of patients who underwent prenatal MMC repair at their institution. METHODS: A retrospective review of all prenatal MMC repair operations performed at the Mayo Clinic between 2012 and 2017 was conducted. Pertinent data regarding the clinical courses of these patients before and after MMC repair were summarized. Outcomes of interest were occurrences of HBH and HCP and the need for intervention. RESULTS: A total of 9 prenatal MMC repair cases were identified. There were 7 cases in which MRI clearly demonstrated prenatal HBH, and of these 86% (6/7) had evidence of HBH reversal after repair and prior to delivery. After a mean postnatal follow-up of 20 months, there were 3 cases of postnatal HCP requiring intervention. One case that failed to show complete HBH reversal after MMC repair required early ventriculoperitoneal shunting. The other 2 cases were of progressive, gradual-onset HCP despite complete prenatal HBH reversal, requiring endoscopic third ventriculostomy with choroid plexus cauterization at ages 5 and 7 months. CONCLUSIONS: Although prenatal MMC repair can achieve HBH reversal in a majority of well-selected cases, the prevention of postnatal HCP requiring intervention appears not to be predicated on this outcome alone. In fact, it appears that in a subset of cases in which HBH reversal is achieved, patients can experience a progressive, gradual-onset HCP within the 1st year of life. These findings support continued rigorous postnatal surveillance of all prenatal MMC repair patients, irrespective of postoperative HBH outcome.

A1 segment hypoplasia associated with cerebral infarction after anterior communicating artery aneurysm rupture.

BACKGROUND: Congenital hypoplasia or absence of the A1 segment of the anterior cerebral artery (ACA) has been associated with increased incidence of berry aneurysms at the anterior communicating artery (Acom) complex. It is not known, however, whether this anatomic variant also predisposes patients to complications after aneurysmal subarachnoid hemorrhage. METHODS: Patients were included for analysis if they presented to our institution for clipping or coiling of an Acom aneurysm between the years of 2001 and 2013. Patients were deemed to have cerebral infarction if a new hypodensity in a vascular distribution was visualized on CT imaging. The association between A1 segmental abnormalities and radiologic infarction was subsequently evaluated in a risk-adjusted manner using stepwise multivariable logistic regression analysis. RESULTS: Of 145 patients who presented with aneurysmal subarachnoid hemorrhage after rupture of an Acom aneurysm, 31 (21.4%) had a hypoplastic or absent A1 segment. On univariate analysis, there was a trend toward an increased rate of radiologic infarction in patients with A1 segment abnormalities (OR=2.11, 95% CI: 0.93-4.79; P=0.0757). On multivariable analysis, a hypoplastic or absent A1 segment was significantly associated with an increased rate of radiologic infarction (OR=2.54, 95% CI: 1.02-6.43; P=0.0466). CONCLUSIONS: Our results suggest that a hypoplastic or absent A1 segment is associated with cerebral infarction following subarachnoid hemorrhage from ruptured Acom aneurysms, indicating a potential need for heightened vigilance and a reduced threshold for therapeutic intervention in patients harboring this abnormality.

Gastrostomy tube placement increases the risk of ventriculoperitoneal shunt infection: a multiinstitutional study.

OBJECTIVEGastrostomy tube placement can temporarily seed the peritoneal cavity with bacteria and thus theoretically increases the risk of shunt infection when the two procedures are performed contemporaneously. The authors hypothesized that gastrostomy tube placement would not increase the risk of ventriculoperitoneal shunt infection. The object of this study was to test this hypothesis by utilizing a large patient cohort combined from multiple institutions.METHODSA retrospective study of all adult patients admitted to five institutions with a diagnosis of aneurysmal subarachnoid hemorrhage between January 2005 and January 2015 was performed. The primary outcome of interest was ventriculoperitoneal shunt infection. Variables, including gastrostomy tube placement, were tested for their association with this outcome. Standard statistical methods were utilized.RESULTSThe overall cohort consisted of 432 patients, 47% of whom had undergone placement of a gastrostomy tube. The overall shunt infection rate was 9%. The only variable that predicted shunt infection was gastrostomy tube placement (p = 0.03, OR 2.09, 95% CI 1.07-4.08), which remained significant in the multivariate analysis (p = 0.04, OR 2.03, 95% CI 1.04-3.97). The greatest proportion of shunts that became infected had been placed more than 2 weeks (25%) and 1-2 weeks (18%) prior to gastrostomy tube placement, but the temporal relationship between shunt and gastrostomy was not a significant predictor of shunt infection.CONCLUSIONSGastrostomy tube placement significantly increases the risk of ventriculoperitoneal shunt infection.

Risk of Ventriculostomy-Associated Hemorrhage in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Anticoagulant Thromboprophylaxis.

BACKGROUND: Patients with subarachnoid hemorrhage (SAH) frequently need a ventriculostomy for treatment of hydrocephalus. In some ICU practices, a ventriculostomy is considered a relative contraindication for subcutaneous heparin. We studied the risk of ventriculostomy-associated hemorrhage and deep venous thrombosis (DVT) in patients with anticoagulant prophylaxis. METHODS: This is a retrospective study of 241 consecutive patients with SAH and ventriculostomies treated at Mayo Clinic, Rochester from 2001 to 2014. DVT and pulmonary emboli (PE) prevention included subcutaneous or intravenous heparin, enoxaparin, dalteparin, and warfarin. The incidence of PE and DVT were noted within 30 days of hospital admission. Hemorrhages were classified as minor or major based on size and mass effect. RESULTS: Fifty-three (22 %) of the 241 patients were on prophylactic doses of anticoagulation while in the intensive care unit. Three of 53 patients on prophylactic anticoagulation had minor hemorrhages and none had major hemorrhages. Four (7.5 %) of 53 patients who received prophylactic anticoagulation versus 34 (18 %) of 188 patients who did not receive prophylactic anticoagulation developed DVT (p = 0.09). One of 10 patients on therapeutic anticoagulation had a major and fatal hemorrhage. CONCLUSION: In our cohort, the risk of VTE was reduced by more than half in patients receiving chemoprophylaxis. Ventriculostomy-associated hemorrhages were rare and minor. Anticoagulant thromboprophylaxis is mostly safe and required in aneurysmal SAH.

Prognostic and Mechanistic Factors Characterizing Seizure-Associated Crossed Cerebellar Diaschisis.

BACKGROUND: Crossed cerebellar diaschisis is a rare finding of hemispheric cerebellar depression following contralateral cerebral injury, hypothesized to result from excessive neuronal excitatory synaptic activity along cortico-pontine-cerebellar pathways. The phenomenon is typically observed following ischemic stroke, but has also been characterized during seizure activity--in particular, status epilepticus (SE). Neurological outcome has varied widely in published reports, with some patients achieving full neurologic recovery, while others experience persistent disability. METHODS: Case report and literature review. RESULTS: We present a 54-year-old man found unresponsive with a right hemispheric syndrome several days after discharge following amygdalohippocampectomy for refractory right temporal lobe epilepsy. Prolonged electroencephalogram demonstrated one subclinical right frontal seizure, along with right frontal periodic lateralized epileptiform discharges, presumed to be associated with SE preceding his admission. Initial MRI demonstrated restricted diffusion on diffusion weighted imaging in the right cerebral hemisphere, ipsilateral thalamus, and contralateral cerebellum. A head CT one week later showed diffuse sulcal effacement with loss of gray-white differentiation in the right frontal and insular regions with low attenuation changes of right thalamus. An MRI showed worsened diffusion restriction, despite a corresponding increase in perfusion. The patient remained paretic at discharge and follow-up. Follow-up MRI at 2 months demonstrated pronounced right cerebral and left cerebellar atrophy, loss of gray matter in much of the right cerebrum, and scattered areas of T2 hyperintensity, consistent with permanent right fronto-temporal neuronal loss. CONCLUSIONS: Collectively, these observations indicate that imaging findings of persistent cerebral restricted diffusion and cytotoxic edema in the subacute post-ictal period may predict irreversible neuronal injury and poor long-term outcome-even when accompanied by evidence of cortical hyperperfusion and recovery of second- and third-order neurons along the involved circuit.

Prompt Recognition and Management of Postoperative Intracranial Hypotension-Associated Venous Congestion: A Case Report.

BACKGROUND: Postoperative intracranial hypotension-associated venous congestion (PIHV) is an uncommon cause of clinical deterioration after a neurosurgical procedure that is often unrecognized until late in its course. Functional outcomes range from remarkable neurological recovery to death. Little is understood about the reason for deterioration in certain patients compared with improvement in others. A 68-year-old man with a progressive cervical myelopathy underwent an uncomplicated cervical decompression and alignment restoration at our hospital and suffered violent generalized tonic-clonic seizures intraoperatively and postoperatively. A postoperative head CT showed a right parietal hematoma, but no other cranial findings. A subsequent MRI demonstrated what we describe as early PIHV with symmetric T2 signal changes in the bilateral deep gray structures. No diffusion restriction corresponded to these areas. A CT myelogram revealed a considerable CSF collection within the operative bed. Upon returning to the operating room to localize the source of the leak, a large dural tear was identified off of midline with a bone chip alongside the defect. The defect was repaired, and the patient remained comatose for over a week postoperatively. He made a remarkable gradual recovery, and after a month in the hospital and rehabilitation, he returned home with relatively minimal neurological deficits. CONCLUSIONS: We postulate that if caught early and treated aggressively, neurologic injury resulting from PIHV may be reversible despite initially ominous imaging. Neurosurgeons and neurointensivists should therefore be compelled to search for dural defects and return to the operating room for immediate repair.