Retained medullary cord and caudal lipoma with histopathological presence of terminal myelocystocele in the epidural stalk.

Background: The retained medullary cord (RMC), caudal lipoma, and terminal myelocystocele (TMCC) are thought to originate from the failed regression spectrum during the secondary neurulation, and the central histopathological feature is the predominant presence of a central canal-like ependyma-lined lumen (CC-LELL) with surrounding neuroglial tissues (NGT), as a remnant of the medullary cord. However, reports on cases in which RMC, caudal lipoma, and TMCC coexist are very rare. Case Description: We present two patients with cystic RMC with caudal lipoma and caudal lipoma with an RMC component, respectively, based on their clinical, neuroradiological, intraoperative, and histopathological findings. Although no typical morphological features of TMCC were noted on neuroimaging, histopathological examination revealed that a CC-LELL with NGT was present in the extraspinal stalk, extending from the skin lesion to the intraspinal tethering tract. Conclusion: This histopathological finding indicates the presence of TMCC that could not be completely regressed and further supports the idea that these pathologies can be considered consequences of a continuum of regression failure during secondary neurulation.

Severe type of segmental spinal dysgenesis with complete disconnection of the spinal cord and vertebra associated with open neural tube defect.

Background: Severe type of segmental spinal dysgenesis (SSD) is a rare and complex anomaly in which the spinal cord completely disconnects at the portion of the spinal dysgenesis. Although closed spinal dysraphisms have been associated with SSD, to the best of our knowledge, the association between open neural tube defect (ONTD) and SSD is significantly rare, with only one case being reported to date. Case Description: We report a case of an infant with severe SSD and a disconnected spinal cord and spinal column at the thoracolumbar junction associated with myelomeningocele (MMC) in the lumbosacral region. The patient presented severe neurological deficits in the legs and impaired bowel function. The spinal column of L1-L3 was absent. The lower spinal segment consisted of neural placode at the L5-S1 level and no connecting structure between the upper and lower spinal cords. A repair surgery for MMC, including cord untethering and dura plasty, was performed. Histopathological findings revealed a neural placode consisting of a neuroglial tissue and leptomeninges. Conclusion: The management of severe SSD during the perinatal period is more challenging when it is associated with ONTD. We report detailed neuroradiological, intraoperative, and histological findings of such a case and discuss the embryopathogenesis of the associated ONTD and the treatment strategies.

A Presenile Patient with Filar Lipoma Who Developed Tethered Spinal Cord Syndrome Triggered by Lumbar Canal Stenosis.

Lumbar canal stenosis (LCS) has been reported as a precipitating factor by which a tethered spinal cord, which is asymptomatic during childhood, develops into tethered cord syndrome (TCS) in adulthood. However, only a few reports on surgical strategies for such cases are available. A 64-year-old woman presented with unbearable pain in the left buttock and dorsal aspect of the thigh approximately 1 year ago. Magnetic resonance imaging showed cord tethering with a filar-type spinal lipoma and LCS due to the thickening of the ligamentum flavum at the L4-5 vertebral level. Five months after the decompressive laminectomy for the treatment of LCS, an untethering surgery was performed at the dural cul-de-sac at the S4 level. The severed end of the filum was elevated rostrally by 7 mm, and the pain subsided postoperatively. This case study shows that surgeries for both lesions should be indicated for adult-onset TCS triggered by LCS.

Ectopic dorsal root ganglion in cauda equina mimicking schwannoma in a child.

Background: A heterotopic dorsal root ganglion (DRG) is sometimes observed in the vicinity of dysplastic neural structures during surgery for open spinal dysraphism; however, it is rarely associated with closed spinal dysraphism. Distinguish from neoplasms by preoperative imaging study is difficult. Although the embryopathogenesis of a heterotopic DRG has been speculated to be migration disorder of neural crest cells from primary neural tube, its details remain unelucidated. Case Description: We report a pediatric case with an ectopic DRG in cauda equina associated with a fatty terminal filum and bifid sacrum. The DRG mimicked a schwannoma in the cauda equina on preoperative magnetic resonance imaging. Laminotomy at L3 revealed that the tumor was entangled in the nerve roots, and small parts of the tumor were resected for biopsy. Histopathologically, the tumor consisted of ganglion cells and peripheral nerve fibers. Ki-67 immunopositive cells were observed at the periphery of the ganglion cells. These findings indicate the tumor comprised DRG tissue. Conclusion: We report detailed neuroradiological, intraoperative and histological findings and discuss the embryopathogenesis of the ectopic DRG. One should be aware of the possibility of ectopic or heterotopic DRGs when cauda equina tumors are observed in pediatric patients with neurulation disorders.

Histopathological presence of dermal elements in resected margins of neural structures obtained from initial repair surgery for myelomeningocele.

Background: Development of dermoid or epidermoid cysts in myelomeningocele (MMC) sites is generally thought to occur in a delayed fashion due to implantation of dermal elements during initial repair surgery. Another theory is that dermal and dermoid elements may already be present within dysplastic neural structures at birth. Methods: We experienced histopathological presence of dermal elements in resected tissues at initial repair surgery in four out of 18 cases with MMC who required resection of parts or margins of the neural structures to perform cord untethering. Since one of these cases has already been reported, we describe the clinicopathological findings for the remaining three cases. Results: In Case1, cryptic dermoid elements were discovered in the terminal filum-like structure (FT-LS) caudal to the open neural placode (NP). The FT-LS had histopathological characteristics similar to the retained medullary cord. In Case 2, dermoid elements were discovered in the caudal margin of the dysplastic conus medullaris. In Case 3, a thin squamous epithelial layer overlapped the rostral margin of the NP where the NP was located near the skin. Case 1 developed an epidermoid cyst at 1 year and 2 months of age, which was totally resected. Conclusion: Prenatally existing cryptic dermoid elements in the caudal portion of neural structures and remnants of dermal elements overlapping the rostral margin of the NP are associated with delayed occurrence of dermoid/ epidermoid cysts. Postoperative histopathological investigation of the resected specimens is recommended. Once dermal elements are revealed, repeated imaging examination and additional surgery should be considered.

Stereo-electroencephalography evidence of an eccentrically located seizure-onset zone around a polymorphous low-grade neuroepithelial tumor of the young: illustrative case.

BACKGROUND: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a newly identified low-grade brain tumor with frequent epileptic presentation. Despite the facilitated use of invasive electroencephalography owing to the growing availability of stereo-electroencephalography (SEEG), intracranial features of tumor-related seizures are still scarcely described. This report provides the first description of SEEG-recorded seizures in PLNTY to provide an insight into its surgical strategy. OBSERVATIONS: Spontaneous clinical seizures were recorded with SEEG in a young adult patient with drug-resistant epilepsy associated with a PLNTY in the left lateral temporal cortex. The seizure onset was characterized by low-voltage fast activity (LVFA) and showed eccentric localization with respect to the tumor: LVFA was localized in the anterior portion of the tumor and spread toward the adjacent polar cortex. The language risks associated with the resection of the posterior temporal cortex could thus be minimized. LESSONS: PLNTY can show a focal and eccentric seizure-onset zone around the tumor. The present findings serve to improve the functional and seizure outcomes using the staged invasive approach in PLNTY.

Intramedullary abscess at thoracolumbar region transmitted from infected dermal sinus and dermoid through retained medullary cord.

BACKGROUND: A retained medullary cord (RMC) is a relatively newly defined entity of closed spinal dysraphism that is thought to originate from regression failure of the medullary cord during secondary neurulation. A congenital dermal sinus (CDS) may provide a pathway for intraspinal infections such as repeated meningitis. Intramedullary abscesses are the rarest but most serious complication of a CDS. CASE DESCRIPTION: We treated a female infant with an intramedullary abscess in the thoracolumbar region, which was caused by infection of the CDS. Surgery revealed that the cord-like structure (C-LS) started from the cord with the intramedullary abscess, extended to the dural cul-de-sac, and further continued to the CDS tract and skin dimple. The boundary between the functional cord and the non-functional CL-S was electrophysiologically identified, and the entire length of the C-LS (the RMC) with an infected dermoid cyst was resected. As a result, the abscess cavity was opened and thorough irrigation and drainage of the pus could be performed. Histopathological examination of the C-LS revealed an infected dermoid cyst and abscess cavity with keratin debris in the fibrocollagenous tissue. The abscess cavity had a central canal-like ependymal lined lumen (CCLELL), with surrounding glial fibrillary acidic protein (GFAP)-immunopositive neuroglial tissues. CONCLUSION: We demonstrated that the transmission of an infection through the RMC was involved in the development of the intramedullary abscess. A good postoperative outcome was obtained because a terminal ventriculostomy for pus drainage could be achieved by excising the nonfunctional RMC.

Retained Medullary Cord Associated with Terminal Myelocystocele and Intramedullary Arachnoid Cyst.

INTRODUCTION: The retained medullary cord (RMC) is a newly defined entity of closed spinal dysraphism that is thought to originate from regression failure of the medullary cord during the last phase of secondary neurulation. The terminal myelocystocele (TMC) is an unusual type of closed spinal dysraphism, characterized by localized cystic dilatation of the terminal part of the central canal that then herniates through a posterior spinal bifida. The co-occurrence of RMC and TMC is extremely rare. CASE PRESENTATION: We treated a baby girl with a huge sacrococcygeal meningocele-like sac with two components. Untethering surgery and repair surgery for the sac revealed that RMC, associated with intramedullary arachnoid cyst (IMAC), was terminated at the bottom of the rostral cyst, forming the septum of the two cystic components, and the caudal cyst was TMC derived from the central canal-like ependymal lining lumen (CC-LELL) of the RMC at the septum. IMAC within the RMC communicated with TMC, and both contained xanthochromic fluid with the same properties. CONCLUSION: We speculated that the mass effect of the coexistent IMAC impeded the flow of cerebrospinal fluid in the CC-LELL within the RMC and eventually formed a huge TMC. In surgical strategies for such complex pathologies, it is important to identify the electrophysiological border between the functional cord and nonfunctional RMC and the severe RMC to untether the cord, as with a typical or simple RMC.

Cerebral Tuberculoma with Mild Posterior Cervical Pain as the Main Symptom Despite Extensive Brain Lesions.

A 59-year-old woman with a diabetes history experienced mild neck pain. A neurological examination revealed only mild neck stiffness. Magnetic resonance imaging showed extensive T2-weighted high-intensity lesions with patchy gadolinium enhancement mainly involving the white matter in the right parietal lobe. A cerebrospinal fluid analysis revealed increased protein levels and pleocytosis. While QuantiFERON-TB Gold was positive, computed tomography (CT) and fluorodeoxyglucose on positron emission tomography-CT of the whole body showed no abnormal accumulation, suggesting tuberculosis. A brain biopsy revealed cerebral tuberculoma. As cerebral tuberculoma can show minimal neurological symptoms despite extensive lesions, a cautious examination and early treatment are required to prevent a devastating prognosis.

A case of ganglioglioma grade 3 with H3 K27M mutation arising in the medial temporal lobe in an elderly patient.

The mutation p.K27M in H3F3A (H3 K27M mutation) is mainly detected in diffuse midline glioma. However, recent studies have demonstrated that H3 K27M mutation could also be observed in a subset of gangliogliomas. Importantly, most H3 K27-mutated ganglioglioma cases also harbor BRAF V600E mutation. Herein, we report a rare case of H3 K27M-mutated ganglioglioma grade 3 without BRAF mutation arising in the medial temporal lobe in an elderly man. A small biopsy specimen was sampled. The pathological diagnosis was diffuse astrocytoma. The tumor progressed gradually during an 18-month follow-up period. Gadolinium enhancement on magnetic resonance imaging was noted 36 months after the biopsy. The patient was referred to a hospital for tumor resection. Histological analysis of resected specimens led to a diagnosis of ganglioglioma grade 3 with H3 K27M mutation. The patient underwent concurrent temozolomide chemotherapy with radiotherapy. Although the patient's condition deteriorated after chemotherapy due to disease progression, he survived for more than 23 months after tumor resection. We present this rare case and discuss the involvement of H3 K27M mutation in ganglioglioma grade 3.

Spinal cord deformity with aggravation of tethering in saccular limited dorsal myeloschisis during the first 2 months of life.

BACKGROUND: Although the optimal timing of prophylactic untethering surgery for limited dorsal myeloschisis (LDM) with intact or subtle neurological findings diagnosed at birth remains undetermined, intentional delayed surgery is commonly used for flat and tail-like LDM. Conversely, for saccular LDM, early surgery is indicated during the postnatal period because it prevents rupture of the sac. We treated a saccular LDM patient, in whom intentional delayed surgery was selected because the sac was thickly covered with normal skin. We describe the clinical course of the case and discuss the optimal timing of the surgery. CASE DESCRIPTION: The patient had a dorsal midline sac in the upper lumbar region. Initial magnetic resonance imaging (MRI) after birth revealed a tethering tract that began at the dome of the sac and joined the lumbar cord. Dorsal bending of the cord at the stalk-cord union and invagination of the cord into the sac were noted. At 2 months, he was neurologically normal; however, the second MRI examination revealed that the cord tethering was aggravated. The cord was markedly displaced dorsally and to the left, with deviation of the cord to the sac out of the spinal canal. Following untethering surgery, the spinal cord deformity markedly improved. CONCLUSION: Early surgery may be recommended for saccular LDM when tethering is present, including dorsal bending of the cord at the stalk-cord union and invagination of the cord into the sac observed on detailed MRI examination, even if the sac has no risk of rupture.

Surgical histopathology of a filar anomaly as an additional tethering element associated with closed spinal dysraphism of primary neurulation failure.

BACKGROUND: Closed spinal dysraphism of primary neurulation failure could be associated with filar anomalies, such as filar lipoma or thickened and tight filum terminale (TFT), resulting from impaired secondary neurulation. Retained medullary cord (RMC) is a remnant of the cavitary medullary cord originating from the secondary neurulation failure. Some filar lipomas are known to contain a central canal-like ependyma-lined lumen with surrounding neuroglial tissues (E-LC w/NGT), that is, a characteristic histopathology of RMC. To clarify the embryological background of these filar anomalies, we evaluated the histopathological findings. METHODS: Among 41 patients with lesions of primary neurulation failure who underwent initial untethering surgery, the filum including cord-like structure (C-LS) was additionally resected in 10 patients (five dorsal and transitional lipomas; five limited dorsal myeloschisis). We retrospectively analyzed the clinical, neuroradiological, intraoperative, and histopathological findings. RESULTS: Among 10 patients, two patients were diagnosed with RMC based on morphological features and intraoperative neurophysiological monitoring. The diagnosis of filar lipoma was made in six patients, since various amounts of fibroadipose tissue were histopathologically noted in the filum. Two patients were diagnosed with TFT, since the filum was composed solely of fibrocollagenous tissue. E-LC w/NGT was noted not only in both C-LSs of RMCs but also in two out of six fila both with filar lipomas and fila with TFTs. CONCLUSION: These findings provide further evidence for the idea that entities, such as filar lipoma, TFT, and RMC, can be considered consequences of a continuum of regression failure occurring during late secondary neurulation.

Acute-phase electroencephalography for an infantile atypical teratoid/rhabdoid tumor.

BACKGROUND: Primary brain tumor is a leading cause of death in cancer-bearing children. Acutely progressive patterns of electroencephalography (EEG) remain to be investigated for children with rapidly growing brain tumors. CASE REPORT: A 14-month-old boy was transferred to our department for prolonged seizures and unrecovered consciousness on his fifth day of illness. The EEG recording on admission showed highly disorganized background activity with high-voltage rhythmic delta waves. Serial EEG monitoring revealed a rapid transition of the background activity to the suppression-burst pattern, and then to generalized suppression of cortical activity within a few hours after admission. Magnetic resonance imaging detected a midline tumor at the pineal gland extending to the midbrain and pons. The tumor was pathologically confirmed as atypical teratoid/rhabdoid tumor (AT/RT) with absent expression of SMARCB1. He died of tumor progression on the 20th day after admission. CONCLUSION: AT/RT is an additional category of brain tumors that cause the clinically and electro-physiologically critical condition in a few days after the onset.

Intraventricular mucin-producing glioblastoma arising in the septum pellucidum at the frontal horn of the lateral ventricle: A case report.

Glioblastoma (GBM) most commonly appears to be intraparenchymal tumor, and intraventricular GBMs are rarely reported. In previous reports, the sites of origin were not identified. Here, we report a rare case of intraventricular mucin-producing GBM in a 73-year-old woman who had a strongly enhancing tumor in the right anterior horn of the lateral ventricle. The tumor had previously been identified one and a half years ago as a small asymptomatic lesion attached to the septum pellucidum. It had been documented to gradually enlarge during subsequent follow-up examinations. The patient underwent a gross total resection of the tumor, and a soft and gelatinous mass was observed. The pathological diagnosis was compatible with GBM, and numerous tumor cells having cytoplasmic mucin vacuoles were observed. Genetic analysis revealed TP53 and NFKBIA deletions. The patient received postoperative concurrent chemotherapy with temozolomide and radiotherapy, followed by maintenance administration of temozolomide. A follow-up examination seven months later detected an asymptomatic local recurrent lesion, which was treated with gamma-knife therapy, followed by bevacizumab administration for six months. The patient has remained clinically well for five years following surgery. The origin of a rare tumor entity, intraventricular GBM, and the specific spatial and pathological findings in our case are discussed in this report.

CD206 Expression in Induced Microglia-Like Cells From Peripheral Blood as a Surrogate Biomarker for the Specific Immune Microenvironment of Neurosurgical Diseases Including Glioma.

Targeting the unique glioma immune microenvironment is a promising approach in developing breakthrough immunotherapy treatments. However, recent advances in immunotherapy, including the development of immune checkpoint inhibitors, have not improved the outcomes of patients with glioma. A way of monitoring biological activity of immune cells in neural tissues affected by glioma should be developed to address this lack of sensitivity to immunotherapy. Thus, in this study, we sought to examine the feasibility of non-invasive monitoring of glioma-associated microglia/macrophages (GAM) by utilizing our previously developed induced microglia-like (iMG) cells. Primary microglia (pMG) were isolated from surgically obtained brain tissues of 22 patients with neurological diseases. iMG cells were produced from monocytes extracted from the patients' peripheral blood. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant correlation of the expression levels of representative markers for M1 and M2 microglia phenotypes between pMG and the corresponding iMG cells in each patient (Spearman's correlation coefficient = 0.5225, P <0.0001). Synchronous upregulation of CD206 expression levels was observed in most patients with glioma (6/9, 66.7%) and almost all patients with glioblastoma (4/5, 80%). Therefore, iMG cells can be used as a minimally invasive tool for monitoring the disease-related immunological state of GAM in various brain diseases, including glioma. CD206 upregulation detected in iMG cells can be used as a surrogate biomarker of glioma.

Clinical implications of molecular analysis in diffuse glioma stratification.

The revised 4th edition of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) has introduced the integrated diagnostic classification that combines molecular and histological diagnoses for diffuse gliomas. In this study, we evaluated the molecular alterations for consecutive 300 diffuse glioma cases (grade 2, 56; grade 3, 62; grade 4, 182) based on this classification. Mutations in the isocitrate dehydrogenase (IDH) genes were common in lower grade glioma (LGG: grade2-3), and when combined with 1p/19q status, LGGs could be stratified into three groups except for four cases (Astrocytoma, IDH-mutant: 44; Oligodendroglioma, IDH-mutant and 1p/19q codeleted: 37; Astrocytoma, IDH-wildtype: 33). 1p/19q-codeleted oligodendrogliomas were clinically the most favorable subgroup even with upfront chemotherapy. In contrast, IDH-wildtype astrocytomas had a relatively worse prognosis; however, this subgroup was more heterogeneous. Of this subgroup, 11 cases had TERT promoter (pTERT) mutation with shorter overall survival than 12 pTERT-wildtype cases. Additionally, a longitudinal analysis indicated pTERT mutation as early molecular event for gliomagenesis. Therefore, pTERT mutation is critical for the diagnosis of molecular glioblastoma (WHO grade 4), regardless of histological findings, and future treatment strategy should be considered based on the precise molecular analysis.

Subpial Lumbar Lipoma Associated with Retained Medullary Cord.

Subpial lipomas, which are also known as nondysraphic intramedullary spinal cord lipomas, are not associated with spinal dysraphism resulting from the failed primary neurulation. Retained medullary cord (RMC) is a newly defined entity of closed spinal dysraphism that originates from the late arrest of secondary neurulation. We treated a 6-year-old boy presented with myoclonus of the lower limbs, who had subpial lipoma at the lumbar cord, just rostral to the low-lying conus, which was tethered by a cord-like structure (C-LS) continuous from the conus and extending to the dural cul-de-sac. Following cord untethering from C-LS and minimal debulking of the lipoma, the myoclonus was improved. Histological examination of C-LS revealed a large central canal-like structure in the neuroglial core and the diagnosis of RMC was made. Subpial lipomas can be incidentally coexistent with spinal dysraphism resulting from the failed secondary neurulation, such as RMC.

Transactivation response DNA-binding protein of 43 kDa proteinopathy and lysosomal abnormalities in spastic paraplegia type 11.

Spastic paraplegia type 11 (SPG11) is the most common autosomal recessive hereditary spastic paraplegia with thinning of the corpus callosum. Spatacsin, a protein encoded by the SPG11 gene, is associated with autophagy. SPG11 patients show spastic paraplegia, intellectual disability, dementia, and parkinsonism. A previous neuropathological analysis of SPG11 cases reported neurodegeneration mimicking amyotrophic lateral sclerosis without transactivation response DNA-binding protein of 43 kDa (TDP-43) deposits and unique sequestosome 1 (SQSTM1)-positive neuronal inclusions. We performed a neuropathological examination of two Japanese patients with complicated spastic paraplegia with thinning of the corpus callosum from different families, and one was genetically diagnosed as having SPG11. Both cases showed diffuse atrophy of the brain and spinal cord. Depigmentation of the substantia nigra was also observed. Immunohistochemistry revealed widespread distribution of areas showing TDP-43 aggregation in the central nervous system. The TDP-43 deposits in the thalamus and substantia nigra especially resembled skein-like inclusions. Unique SQSTM1-positive neuronal inclusions, as previously reported, were widespread in the whole central nervous system as well as the dorsal root ganglia. Double-labeling immunofluorescence of the dorsal root ganglia revealed that the unique, large SQSTM1-positive cytoplasmic inclusions of the ganglion cells were labeled with lysosome-associated membrane protein 1 and lysosome-associated membrane protein 2. This is the first report showing TDP-43 pathology in SPG11. The common neuropathological findings of TDP-43-positive inclusions in both the cases imply a causal connection between the TDP-43 proteinopathy and autophagy dysfunction in SPG11.