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.

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.

Diagnostic accuracy for the epileptogenic zone detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT.

OBJECTIVES: To examine the utility of FDG-PET/MRI in patients with epilepsy by comparing the diagnostic accuracy of PET/MRI and PET/CT in epileptogenic zone (EZ) detection. METHODS: This prospective study included 31 patients (17 males, 14 females) who underwent surgical resection for EZ. All patients were first scanned using FDG-PET/CT followed immediately with FDG-PET/MRI. Two series of PET plus standalone MR images were interpreted independently by five board-certified radiologists. A 4-point visual score was used to assess image quality. Sensitivities and visual scores from both PETs and standalone MRI were compared using the McNemar test with Bonferroni correction and Dunn's multiple comparisons test. RESULTS: The EZs were confirmed histopathologically via resection as hippocampal sclerosis (n = 11, 35.5%), gliosis (n = 8, 25.8%), focal cortical dysplasia (n = 6, 19.4%), and brain tumours (n = 6, 19.4%) including cavernous haemangioma (n = 3), dysembryoplastic neuroepithelial tumour (n = 1), ganglioglioma (n = 1), and polymorphous low-grade neuroepithelial tumour of the young (n = 1). The sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). The visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT, as well as standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3). CONCLUSIONS: The diagnostic accuracy for the EZ detection in focal epilepsy could be higher in FDG-PET/MRI than in FDG-PET/CT. KEY POINTS: • Sensitivity of FDG-PET/MRI was significantly higher than that of FDG-PET/CT and standalone MRI (FDG-PET/MRI vs. FDG-PET/CT vs. standalone MRI; 77.4-90.3% vs. 58.1-64.5% vs. 45.2-80.6%, p < 0.0001, respectively). • Visual scores derived from FDG-PET/MRI were significantly higher than those of FDG-PET/CT and standalone MRI (2.8 ± 1.2 vs. 2.0 ± 1.1 vs. 2.1 ± 1.2, p < 0.0001, respectively). • Compared to FDG-PET/CT, FDG-PET/MRI increased the visual score (51.9%, increased visual scores of 2 and 3).

Detection of cutaneous prion protein deposits could help diagnose GPI-anchorless prion disease with neuropathy.

BACKGROUND AND PURPOSE: To investigate prion protein (PrP) deposits in cutaneous tissues of patients of glycosylphosphatidylinositol (GPI)-anchorless prion diseases with neuropathy. METHODS: Cutaneous tissue samples from three patients with GPI-anchorless prion diseases were obtained, two cutaneous biopsy samples from the lower leg of Case 1 (Y162X) and Case 3 (D178fs25), and a cutaneous sample taken from the abdomen during an autopsy of Case 2 (D178fs25). We performed immunohistochemistry for PrP to look for abnormal PrP deposits. RESULTS: PrP deposits were observed in the dermal papilla, the sweat glands, the hair follicles, the arrector pili muscles, and peripheral nerves of all examined cases of GPI-anchorless prion disease with neuropathy. The abnormal PrP accumulation was frequently localized at the basement membrane, and colocalized with laminin. CONCLUSION: Immunohistochemical detection of PrP in cutaneous samples could be used to definitively diagnose GPI-anchorless PrP disease with neuropathy.

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.

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.

Symmetrical glial hyperplasia in the brainstem of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disease, characterized by the progressive ossification of skeletal muscles, fascia, tendons, and ligaments. In most cases, the great toes of patients show symmetrical congenital malformations. The causative gene for FOP has been identified as the activin A receptor, type 1 (ACVR1) gene (ACVR1). The ACVR1 R206H mutation is the most common mutation among FOP patients, and the ACVR1 G356D mutation has been identified as a rare mutation in a Japanese FOP patient with slow progression. In addition to musculoskeletal abnormalities, a series of autopsy studies described one FOP case, without genetic testing to identify ACVR1 mutation, showing nodular heterotopia at the edge of the fourth ventricle. Here, we report the general autopsy findings for a 75-year-old man with FOP, caused by the ACVR1 G356D mutation, including the precise examination of brainstem lesions. Postmortem examination revealed unique symmetrical glial hyperplasia of the pons and medulla oblongata. Microscopically, lesions of the pons involving residual neurons and lesions of the medulla oblongata consisted of subependymal cells. Immunohistochemical analysis of these lesions revealed developmental anomalies, with different cellular components. In this report, for the first time, we present the neuropathological description of a patient with genetically confirmed FOP and symmetrical glial hyperplasia of the pons and medulla oblongata. The presented pathological findings, in conjunction with previous reports implying that the glial hyperplasia of the brainstem is common in FOP, suggest that ACVR1 may play an unclarified developmental role in the human brainstem.

First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide.

INTRODUCTION: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. METHODS: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ-BEV], and the correlations of prognostic factors with survival were evaluated. RESULTS: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ-BEV, 12.2 vs. 16.7 months; P = 0.04). CONCLUSIONS: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.

Differentiation of high-grade from low-grade diffuse gliomas using diffusion-weighted imaging: a comparative study of mono-, bi-, and stretched-exponential diffusion models.

PURPOSE: Diffusion-weighted imaging (DWI) plays an important role in the preoperative assessment of gliomas; however, the diagnostic performance of histogram-derived parameters from mono-, bi-, and stretched-exponential DWI models in the grading of gliomas has not been fully investigated. Therefore, we compared these models' ability to differentiate between high-grade and low-grade gliomas. METHODS: This retrospective study included 22 patients with diffuse gliomas (age, 23-74 years; 12 males; 11 high-grade and 11 low-grade gliomas) who underwent preoperative 3 T-magnetic resonance imaging from October 2014 to August 2019. The apparent diffusion coefficient was calculated from the mono-exponential model. Using 13 b-values, the true-diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction were obtained from the bi-exponential model, and the distributed-diffusion coefficient and heterogeneity index were obtained from the stretched-exponential model. Region-of-interests were drawn on each imaging parameter map for subsequent histogram analyses. RESULTS: The skewness of the apparent diffusion, true-diffusion, and distributed-diffusion coefficients was significantly higher in high-grade than in low-grade gliomas (0.67 ± 0.67 vs. - 0.18 ± 0.63, 0.68 ± 0.74 vs. - 0.08 ± 0.66, 0.63 ± 0.72 vs. - 0.15 ± 0.73; P = 0.0066, 0.0192, and 0.0128, respectively). The 10th percentile of the heterogeneity index was significantly lower (0.77 ± 0.08 vs. 0.88 ± 0.04; P = 0.0004), and the 90th percentile of the perfusion fraction was significantly higher (12.64 ± 3.44 vs. 7.14 ± 1.70%: P < 0.0001), in high-grade than in low-grade gliomas. The combination of the 10th percentile of the true-diffusion coefficient and 90th percentile of the perfusion fraction showed the best area under the receiver operating characteristic curve (0.96). CONCLUSION: The bi-exponential model exhibited the best diagnostic performance for differentiating high-grade from low-grade gliomas.

A case of diffuse midline glioma, H3 K27M mutant mimicking a hemispheric malignant glioma in an elderly patient.

Diffuse midline glioma, H3 K27M mutant arises from midline structures of the central nervous system and predominately affects pediatric patients. However, this disease entity was only recently established, and the clinical phenotypic spectrum remains largely unclear. We herein report a rare case of diffuse midline glioma, H3 K27M mutant with an unusual distribution in an elderly woman who presented with a diffuse glioma that invaded both sides of the thalami, and left hippocampus and frontoparietal lobes, thus mimicking a hemispheric malignant glioma. A biopsy of the lobular lesion led to a molecular diagnostic confirmation of diffuse midline glioma, H3 K27M mutant. The patient received concurrent bevacizumab and temozolomide therapy with radiation therapy and survived for 30 months. This case highlights the possibility that a glioma with cerebral hemispheric spread in an elderly patient may harbor the H3 K27M mutation.

A juvenile case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation.

Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAFA598T mutation, the first case reported in a glioma. BRAFA598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.

Retained medullary cord with sacral subcutaneous meningocele and congenital dermal sinus.

BACKGROUND: A retained medullary cord (RMC) is a rare closed spinal dysraphism with a robust elongated cord-like structure extending continuously from the conus medullaris to the dural cul-de-sac that is caused by late arrest of secondary neurulation. Five patients with RMC extending to an associated sacral subcutaneous meningocele have been reported. CASE PRESENTATION: We report an additional patient with RMC, in whom a congenital dermal sinus (CDS) was found in the caudal portion of the RMC. At the age of 3 days, the patient underwent surgery consisting of meningocele excision and cord untethering, and CDS was noted histologically in the proximal cut end of the RMC. During a second surgery at the age of 5 months, after determining the exact border of the nonfunctional RMC and the true conus by neurophysiological mapping, we removed the entire length of the remnant RMC, including newly developed epidermoid cysts in the CDS. CONCLUSION: Although the exact pathoembryogenesis of concurrent RMC and CDS is unknown, an associated subcutaneous meningocele, caused by failure of primary neurulation, could be involved. Surgeons should be aware of the possibility of the coexistence of CDS when dealing with RMCs that extend out to the extradural space.

Congenital interdural arachnoid cyst of the tentorium cerebelli.

BACKGROUND: Intracranial interdural cyst is a rare lesion. The exact pathophysiology of these cysts remains unknown. CLINICAL PRESENTATION: We report an infant with interdural cyst of the tentorium cerebelli. Although the cyst mimicked an arachnoid cyst on pre- and postnatal magnetic resonance images, lateral suboccipital craniotomy revealed the cyst within the tentorium. Fenestration on the infratentorial side was performed with successful results. Histologically, the inner surface of the cyst was lined with arachnoid cells. CONCLUSION: We report detailed neuroradiological, intraoperative, and histological findings, and discuss the pathophysiology of the cyst in this case.

Ruptured dermoid cyst of the conus medullaris in the myelomeningocele sac revealed at the initial repair surgery.

BACKGROUND: Dermoid cysts in the myelomeningocele (MMC) site are thought to arise in a delayed fashion because of iatrogenic implantation of dermoid elements at the time of the initial repair surgery. However, there have been few reports on dermoid elements already present at birth. CLINICAL PRESENTATION: We report a patient, in whom dermoid cyst was located at dorsal aspect of the conus medullaris in the MMC sac. Between 23+3 and 24+4 weeks of gestation, rupture of the MMC sac occurred. At this time of gestation, we speculate that rupture of the dermoid cyst also occurred and dissemination of the cyst contents caused chemical arachnoiditis in the MMC sac. At the age of 1 day, surgery to repair MMC and postoperative histological findings revealed these rare pathologies. CONCLUSION: Physicians should be aware of the possibility of rupture of a dermoid cyst in the MMC sac during fetal period.

Terminal syringomyelia associated with lumbar limited dorsal myeloschisis.

PURPOSE: Limited dorsal myeloschisis (LDM) is characterized by a fibroneural tethering stalk linking the skin lesion to the underlying spinal cord. Terminal syringomyelia, which is located at the lower third of the cord, is often associated with a tethered cord caused by various spinal dysraphisms; however, terminal syringomyelia has not been documented in LDM. The purpose of this study was to clarify the pathophysiological mechanisms of syringomyelia in LDM. METHODS: In our 16 patients with lumbar LDM, three patients had terminal syringomyelia. We retrospectively analyzed the clinical, neuroradiological, intraoperative, and histopathological findings for these patients, with particular attention to the clinical course of the syrinx. RESULTS: Patient 1 had a saccular skin lesion and patients 2 and 3 had flat lesions. In all patients, the syringomyelic cavity was located in the lower thoracolumbar cord, immediately rostral to the stalk-cord attachment at the lumbar level. The caudal pole of the syrinx extended to the thickened stalk at the attachment instead of at the caudal cord. Patient 3 had another syrinx in the stalk itself. The longitudinal axis of the syrinx and central canal coincided with the traveling angle of the LDM stalk at the stalk-cord attachment. In patient 1, histology revealed an ependyma-lined central canal in both the LDM stalk and meningocele sac. Patients 1 and 2 underwent syringostomy, but long-term effects were not obtained. Preoperative spontaneous resolution occurred in patient 3. CONCLUSIONS: The histological findings in patient 1 supported the idea that segmental myelocystocele is involved in the development of saccular LDM. The hydromyelic central canal herniates and distends the stalk, resulting in the formation of the myelocystocele. It is possible that the hydromyelic central canal also distends the stalk of flat LDM lesions. The syrinx in patient 3 differed from that in patients 1 and 2, in that the syrinx resolved spontaneously. Further studies are needed to clarify the outcomes of syrinxes associated with LDM stalks.

Congenital Dermal Sinus Elements in Each Tethering Stalk of Coexisting Thoracic Limited Dorsal Myeloschisis and Retained Medullary Cord.

INTRODUCTION: The embryogenesis of limited dorsal myeloschisis (LDM) likely involves impaired disjunction between the cutaneous and neural ectoderms during primary neurulation. Because LDM and congenital dermal sinus (CDS) have a shared origin in this regard, CDS elements can be found in the LDM stalk. Retained medullary cord (RMC) is a closed spinal dysraphism involving a robust, elongated, cord-like structure extending from the conus medullaris to the dural cul-de-sac. Because the RMC is assumed to be caused by impaired secondary neurulation, concurrent RMC and CDS cannot be explained embryologically. In the present article, we report a case in which CDS elements were noted in each tethering stalk of a coexisting LDM and RMC. CASE PRESENTATION: A 2.5-month-old boy with left clubfoot and frequent urinary and fecal leakage had 2 tethering tracts. The upper tract, which ran from the thoracic tail-like cutaneous appendage, had CDS elements in the extradural stalk and a tiny dermoid cyst in the intradural stalk immediately after the dural entry. In the lower tract, which ran from the lumbosacral dimple, the CDS as an extradural stalk continued to the RMC at the dural cul-de-sac. Both stalks were entirely resected through skip laminotomy/laminectomy at 1 stage to untether the cord and resect the CDS elements. CONCLUSION: Surgeons should be aware that CDS elements, in addition to LDM, may coexist with RMC that extends out to the extradural space.

A Dorsally Located Endodermal Cyst in the Foramen Magnum Mimicking an Arachnoid Cyst: A Case Report.

INTRODUCTION: Endodermal cysts are congenital benign cystic lesions in the central nervous system and cause various symptoms. Although some have been reported in the posterior fossa, endodermal cysts located dorsal to the brainstem are extremely rare. CASE PRESENTATION: The case was of a 10-year-old girl who presented with bilateral upper limb weakness and tremor. Magnetic resonance imaging demonstrated a 4.5-cm cystic lesion with T1-weighted hypointense and T2-weighted hyperintense content in the midline of the cisterna magna dorsal to the medulla oblongata. The cyst was cerebrospinal fluid-like, causing us to suspect a symptomatic arachnoid cyst. The lucent cyst wall had no apparent attachment, and complete recovery ensued following total excision of the cyst wall. Pathology confirmed a diagnosis of endodermal cyst. DISCUSSION/CONCLUSION: Herein, we review the past literature on this rare entity. An endodermal cyst in the cisterna magna tends to be less strongly attached and to show a cerebrospinal fluid-like component on magnetic resonance images that mimics an arachnoid cyst. The characteristics of dorsally located endodermal cysts may differ from those in other locations.

Neurosurgical Pathology and Management of Limited Dorsal Myeloschisis Associated with Congenital Dermal Sinus in Infancy.

BACKGROUND: Because of the shared origin of limited dorsal myeloschisis (LDM) and congenital dermal sinus (CDS), CDS elements may be found within the fibroneural LDM stalk. When part of the CDS invested in the intradural stalk is left during untethering surgery, inclusion tumors such as dermoid cysts may develop. However, the most appropriate surgical strategy for LDM with CDS is still under debate. METHODS: Of 19 patients with LDM, 3 (15.8%) had histologically verified CDS elements. We retrospectively analyzed the clinicopathological findings of these patients. RESULTS: In patient 1, the entire stalk including a tiny dermoid cyst at the intradural stalk could be resected through two-level laminectomy during untethering at 6 months of age. In patients 2 and 3, the stalk appeared to be a typical LDM stalk during the initial surgery at 18 and 7 days, respectively; however, CDS was histologically diagnosed in the proximal severed end of the stalk. Postoperative three-dimensional heavily T2-weighted imaging demonstrated spherical enlargement of the remnant stalk, and the entire length of the remnant stalk including newly developed dermoid was resected during the second surgery at 3 years 11 months and 11 months, respectively. Histopathologically, glial fibrillary acidic protein-immunopositive neuroglial tissues and CDS elements were mainly located at the proximal and distal sites of the stalk, respectively, supporting the "dragging down and pulling up" theory. In patients 2 and 3, however, the proximal head of the dermoid cyst passed the distal head of the neuroglial tissues and located at the stalk-cord attachment. CONCLUSION: Surgeons should be aware of the approximately 10% possibility of the coexistence of CDS when managing infant LDM. However, the recommendation for excision of the entire length of the LDM stalk in all patients should be more carefully made because such a strategy may result in an unnecessary extent of laminotomy/laminectomy for most patients with pure LDM. However, once the postoperative histological examination reveals coexistence of CDS in the resected proximal part of the stalk, the entire length of the remnant stalk should be excised as soon as possible.

Subcortical axonal loss with glial reactions following partial status epilepticus with neuroradiological findings of reduced subcortical diffusion.

Hyperintensity in the subcortical white matter on the diffusion-weighted magnetic resonance image has been described recently, in association with partial status epilepticus. Although this reduced subcortical diffusion is typically seen in patients with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), the exact pathophysiological mechanism is unclear. We report the case of a 3-month-old boy who underwent surgery for intractable epilepsy associated with cortical dysplasia in the left peri-Rolandic area, coincident with the appearance of reduced subcortical diffusion. Neurohistological findings revealed that the most prominent finding was axonal loss with marked astroglial and microglial reactions in the white matter. Neither degenerated neurons nor neurophagocytic microglial accumulation was evident in the cortex. These findings confirm that white matter can be secondarily damaged in patients with partial status epilepticus, and possible pathomechanism of reduced subcortical diffusion is discussed.

Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2-positive nuclear inclusions in all examined cases. Localization of poly (rC)-binding protein 1 (PCBP1) in 1C2-positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2-positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS-related familial amyotrophic lateral sclerosis.