Nobutaka Mukae

Neurosurgical management and pathology of lumbosacral lipomas with tethered cord

Lumbosacral lipomas are the most common form of occult spinal dysraphism. The development of lumbosacral lipomas is from the premature disjunction of the neural tube from the surrounding ectoderm, leaving the neural plate open posteriorly and allowing for the infiltration of mesodermal tissue, including fatty tissue. Since lumbosacral lipomas are a common cause of spinal cord tethering that can lead to progressive neurological deficits, prophylactic neurosurgery for lumbosacral lipomas, including untethering of the spinal cord, is recommended. We briefly review the embryology, classification, clinical presentation, imaging evaluation, surgical indication, neurosurgical management and pathological examination that are involved in recognizing these complicated malformative pathologies.

Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin

Objectives This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. Methods We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. Results DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). Conclusions This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies.

Neurosurgical pathology of limited dorsal myeloschisis

PurposeThe term limited dorsal myeloschisis (LDM) was used by Pang et al. (2010) to describe a distinct clinicopathological entity. LDMs are characterized by two invariable features: a focal-closed neural tube defect and a fibroneural stalk that links the skin lesion to the underlying spinal cord.MethodsWe retrospectively analyzed the neurosurgical pathologic findings of four LDM patients.ResultsCase 1 had a saccular skin lesion with nonterminal abortive myelocystocele at T11–12. Cases 2, 3, and 4 had a non-saccular (flat) skin lesion in the lumbosacral region. The morphologic features of the lesion in case 2 were those of meningocele manque. Cases 3 and 4 had accompanying non-LDM anomalies, caudal-type lipoma and type II split-cord malformation with neurenteric cyst, respectively. At preoperative diagnosis of the LDM stalk, magnetic resonance imaging, including 3D heavily T2-weighted image was useful; however, minute findings were often missed in the complicated cases 3 and 4. All patients had a favorable outcome following untethering of the stalk from the cord. The central histopathological feature of the LDM stalk is neuroglial tissue in the fibrocollagenous band; however, the stalk in cases 2 and 4 did not have glial fibrillary acidic protein-immunopositive neuroglial tissues.ConclusionsTherefore, the diagnosis of LDM should be made based on comprehensive evaluation of histologic and clinical findings.

Retained medullary cord extending to a sacral subcutaneous meningocele

BackgroundA retained medullary cord (RMC) is a rare closed spinal dysraphism with a robust elongated neural structure continuous from the conus and extending to the dural cul-de-sac. One case extending down to the base of a subcutaneous meningocele at the sacral level has been reported.Clinical presentationWe report on three cases of closed spinal dysraphism, in which a spinal cord-like tethering structure extended out from the dural cul-de-sac and terminated at a skin-covered meningocele sac in the sacrococcygeal region, which was well delineated in curvilinear coronal reconstructed images of 3D-heavily T2-weighted images (3D-hT2WI). Intraoperative neurophysiology revealed the spinal cord-like tethering structure was nonfunctional, and histopathology showed that it consisted of central nervous system tissue, consistent with RMC. The tethering structure histologically contained a glioneuronal core with an ependymal-like lumen and smooth muscle, which may indicate developmental failure during secondary neurulation.ConclusionsWhen the RMC extending to a meningocele is demonstrated with the detailed magnet resonance imaging including 3D-hT2WI, decision to cut the cord-like structure for untethering of the nervous tissue should be made under careful intraoperative neurophysiological monitoring.

Optimal perioperative management of antithrombotic agents in patients with chronic subdural hematoma

OBJECTIVE The use of antithrombotic agents such as anticoagulants and antiplatelet agents is widespread, and the opportunities to treat patients with chronic subdural hematoma (CSDH) under antithrombotic therapy are growing. However, whether antithrombotic therapy contributes to postoperative complications and recurrences of CSDH and how these agents should be managed in the surgical treatment of CSDH remains unclear. METHODS We retrospectively analyzed 150 consecutive patients with CSDH who underwent neurosurgical interventions at Kyushu Rosai Hospital from 2011 to 2015 and followed them for more than 3 months. RESULTS Of the 150 study patients, 44 received antithrombotic therapy. All anticoagulants and 76% of the antiplatelet agents were discontinued before surgical treatment of CSDH and resumed within 1 week except in 4 patients whose treatment was terminated and 7 patients who developed postoperative complications or underwent reoperations before resumption of these agents. Postoperative hemorrhagic complications associated with surgical treatment of CSDH occurred in 8 patients (5.3%), and there was no significant difference in the incidence of these complications between patients with and without antithrombotic therapy (6.8% vs. 4.7%, respectively; p=0.90). Postoperative thromboembolic complications occurred in 5 patients (5.4%), including 4 patients with antithrombotic therapy; these complications developed before resumption of antithrombotic agents in 2 patients. There was a significant difference in the incidence of postoperative thromboembolic complications between patients with and without antithrombotic therapy (9.1% vs. 0.9%, respectively; p=0.04). There were no significant differences in the incidence of radiographic deterioration or reoperation of ipsilateral or contralateral hematomas between patients with and without antithrombotic therapy after surgical treatment of unilateral CSDH. CONCLUSION A history of antithrombotic therapy was significantly correlated with the incidence of postoperative thromboembolic complications in patients with CSDH. Antithrombotic agents should be resumed as soon as possible when no hemorrhagic complication is confirmed after neurosurgical intervention for CSDH.

High-resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas

Craniopharyngioma consists of adamantinomatous and papillary subtypes. Recent genetic analysis has demonstrated that the two subtypes are different, not only in clinicopathological features, but also in molecular oncogenesis. Papillary craniopharyngioma (pCP) is characterized by a BRAF mutation, the V600E (Val 600 Glu) mutation. Adamantinomatous craniopharyngioma (aCP) can be distinguished by frequent β‐catenin gene (CTNNB1) mutations. Although these genetic alterations can be a diagnostic molecular marker, the precise frequency of these mutations in clinical specimens remains unknown. In this study, we first evaluated BRAF V600E and CTNNB1 mutations in four and 14 cases of pCP and aCP, respectively, using high‐resolution melting analysis followed by Sanger sequencing. The results showed that 100% (4/4) of pCP cases had BRAF V600E mutations, while 78% (11/14) of the aCP cases had CTNNB1 mutations, with these genetic alterations being subtype‐specific and mutually exclusive. Second, we evaluated BRAF V600E and CTNNB1 mutations by immunohistochemical analysis (IHC). All pCP cases showed positive cytoplasmic staining with the BRAF V600E‐mutant antibody (VE‐1), whereas 86% (12/14) of aCP cases showed positive cytoplasmic and nuclear staining for CTNNB1, suggesting a CTNNB1 mutation. Only one case of wild‐type CTNNB1 on the DNA analysis showed immunopositivity on IHC. We did not detect a coexistence of BRAF V600E and CTNNB1 mutations in any single tumor, which indicated that these genetic alterations were mutually exclusive. We also report our modified IHC protocol for VE‐1 staining, and present the possibility that BRAF V600E mutations can be used as a diagnostic marker of pCP in the differentiation of Rathke cleft cyst with squamous metaplasia.

Surgical histopathology of limited dorsal myeloschisis with flat skin lesion

PurposeLimited dorsal myeloschisis (LDM) is characterized by two invariable features: a focal closed neural tube defect and a fibroneural stalk linking the skin lesion to the underlying spinal cord. Although detailed histopathological findings of the LDM stalk were originally described by Pang et al., the precise relationship between the histopathological findings and clinical manifestations including intraoperative findings has not been fully determined.MethodsWe retrospectively analyzed the histopathological findings of the almost entire stalk and their relevance to the clinical manifestations in six Japanese LDM patients with flat skin lesions.ResultsGlial fibrillary acidic protein (GFAP)-immunopositive neuroglial tissues were observed in three of the six patients. Unlike neuroglial tissues, peripheral nerve fibers were observed in every stalk. In four patients, dermal melanocytosis, “Mongolian spot,” was seen surrounding the cigarette-burn lesion. In three of these four patients, numerous melanocytes were distributed linearly along the long axis of the LDM stalk, which might represent migration of melanocytes from trunk neural crest cells during formation of the LDM stalk.ConclusionImmunopositivity for GFAP in the LDM stalk was observed in as few as 50% of our patients, despite the relatively extensive histopathological examination. We confirm that the clinical diagnosis of LDM should be made based on comprehensive histopathological examination as well as clinical manifestations. The profuse network of peripheral nerve fibers in every stalk and the high incidence of melanocyte accumulation associated with dermal melanocytosis might assist the histopathological diagnosis of LDM.

Radiological features of brain metastases from non-small cell lung cancer harboring EGFR mutation

Aim: To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Patients and Methods: Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT. Results: Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037). Conclusion: Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain.

Hemodynamic state of periictal hyperperfusion revealed by arterial spin-labeling perfusion MR images with dual postlabeling delay

Background Magnetic resonance imaging (MRI), including perfusion MRI with arterial spin labeling (ASL) and diffusion-weighted imaging (DWI), are applied in the periictal detection of circulatory and metabolic consequences associated with epilepsy. Although previous report revealed that prolonged ictal hyperperfusion on ASL can be firstly detected and cortical hyperintensity of cytotoxic edema on DWI secondarily obtained from an epileptically activated cortex, the hemodynamic state of the periictal hyperperfusion has not been fully demonstrated. Methods: study-1 We retrospectively analyzed the relationship between seizure manifestations and the development of periictal MRI findings, in Case 1 with symptomatic partial epilepsy, who underwent repeated periictal ASL/DWI examination for three epileptic ictuses (one examination for each ictus). Study-2: We evaluated the hemodynamic state of periictal hyperperfusion with the ASL technique using a dual postlabeling delay (PLD) of 1.5 and 2.5 s in nine patients, according to the presence or absence of the localized epileptogenic lesion (EL) on conventional 3 T-MRI, who were divided into Group EL+ (six patients) and Group EL− (three patients). Results Study-1 confirmed that the stratified representation of the periictal MRI findings depends on the time interval between the ictal cessation and MRI examination in addition to the magnitude and duration of the epileptic activity. In Study-2, two types of periictal hyperperfusion were noted. In all six Group EL+ patients, periictal ASL findings showed “fast flow type”. Markedly increased ASL signals were noted at the epileptically activated cortex, having a tight topographical relationship with EL, on ASL with a PLD of 1.5 s, which is decreased on ASL with a PLD of 2.5 s. In all three Group EL− patients, periictal ASL findings showed “gradual flow type”, which is characterized by gradual signal increase of the epileptically activated cortex on ASL with a PLD of 1.5 and 2.5 s. Conclusion We confirmed that ASL hyperperfusion is superior to DWI in the periictal detection of epileptic events. ASL with dual PLD offers the ability to document two types of hemodynamics of periictal hyperperfusion.

Bony and Cartilaginous Tissues in Lumbosacral Lipomas

Purpose: It is well known that bony and cartilaginous tissues can be present in lumbosacral lipomas; however, the relationship between their presence and clinical features has not been demonstrated. Methods: Five (10.4%) out of 48 patients had osteochondral tissues in lipomas. We retrospectively analyzed the clinical, neuroradiological, and histological findings of these patients. Results: Five (45.5%) of 11 patients with dorsal and transitional type lipomas had osteochondral tissues, while none with caudal and filar type lipomas had these tissues. Presurgical imaging demonstrated that the osteochondral tissue was located in a large subcutaneous lipoma dorsal to the bifid vertebral column. Histologically, mature bone with hematopoietic marrow and hyaline cartilage were observed in 3 and 2 patients, respectively. Conclusions: The high incidence of association of osteochondral tissues with dorsal and transitional type lipomas is thought to be the result of primary neurulation failure with invasion of mesenchymal tissues. Caudal and filar type lipomas, resulting from secondary neurulation failure, thus did not have osteochondral tissue.