Spinal endodermal cyst undergoing malignant transformation and marked elevation of serum carbohydrate 19-9 level.

Endodermal cyst (EC) is a benign tumor that can arise along the craniospinal axis. Infrequently, ECs undergo malignant transformation. A 43-year-old man presented with numbness in the right arm, leg and occipitalgia. MRI revealed a multicystic, intradural extramedullary tumor at C2 with enhancement along the ventral surface of the spinal cord. Blood test showed an abnormal increase in serum carbohydrate antigen 19-9 (CA 19-9) level. Systemic positron emission tomography-computed tomography was normal. He underwent total tumor resection and was diagnosed with EC. He developed double vision, hearing loss, and swallowing difficulty on postoperative day 70. Cerebral MRI revealed marked extensions of leptomeningeal dissemination. The serum CA 19-9 level increased continuously and finally reached 1515.0 U/ml. He died of respiratory failure on day 108. An autopsy did not reveal abnormalities in the abdominal and chest organs. On microscopic examination, the post-mortem specimen revealed adenocarcinoma. Immunohistochemically, both the surgical and autopsy specimens were positive for CA 19-9. Spinal ECs may lead to malignant transformation with leptomeningeal dissemination that causes abnormal elevation of serum CA 19-9 levels.

Low‒Risk Essential Thrombocythemia Who Presented with Recurrent Episodes of Cerebral Hemorrhage during Pregnancy and Developed Cerebral Infarction during Puerperium.

A 42‒year‒old woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/µL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/µL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/µL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/µL. Six days after delivery, she developed infarction. The Plt count was 915,000/µL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/µL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"low‒risk"by IPSET‒thrombosis, and as"ultralow"risk by revised IPSET‒thrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.

Pediatric Idiopathic Intervertebral Disc Calcification: Single-Center Series and Review of the Literature.

OBJECTIVE: To review pediatric idiopathic intervertebral disc calcification (PIIVDC) within a single center and within the literature to outline the disease course, management, and outcome. STUDY DESIGN: A retrospective chart review was performed spanning the period between January 2001 and February 2016 for diagnoses of PIIVDC. Patient age, sex, symptoms, and history and physical and neurologic findings were reviewed. Laboratory and imaging findings, management, follow-up, and outcome also were studied. RESULTS: Nine cases of PIIVDC were identified; they included 6 male and 3 female patients, with an age range of 23 months to 12 years. Two patients were asymptomatic, and PIIVDC was discovered incidentally. Of the remaining 7 patients, 5 presented with neck and/or back pain, 1 with painless torticollis, and 1 with painful torticollis. One patient reported neurologic symptoms of pain radiating along 1 dermatome. Disc spaces affected were 5 cervical, 4 thoracic, and 2 lumbar, with 2 patients having more than 1 space affected. All patients were managed conservatively. In 1 case, symptoms and lesions persisted after 5 years, but the remainder had complete symptom resolution, generally within 6 months. CONCLUSIONS: The etiology of PIIVDC remains unknown but appears to occur spontaneously, without preceding trauma or underlying medical condition. A conservative approach to patients without severe neurologic deficit with outpatient follow-up is supported.

The role of surgery in refractory epilepsy secondary to polymicrogyria in the pediatric population.

OBJECTIVE: Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG. METHODS: A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed. RESULTS: A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow-up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure-free at last follow-up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%). SIGNIFICANCE: We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG.

Spinal Dural Arteriovenous Fistula Assumed to be Symptomatic after Placement of Lumbar Cerebrospinal Fluid Drain.

A 69-year-old man presented with severe headache. Cranial computed tomography revealed diffuse subarachnoid hemorrhage. An anterior communicating artery aneurysm was identified and successfully obliterated by open microsurgery on the same day. Following placement of a continuous lumbar cerebrospinal fluid drain on hospitalization day 7, the patient developed a severe paraplegia and sensory loss below T6. Cerebral magnetic resonance imaging did not identify a responsible lesion. Spinal magnetic resonance imaging, however, showed extensive intramedullary hyperintensity on T2-weighted sequences. Spinal angiography identified a dural arteriovenous fistula fed by the segmental artery branching with the 12th intercostal artery. It was successfully embolized and the patient's sensorimotor disturbances remarkably improved. A spinal dural arteriovenous fistula may better be considered as one of the underlying etiologies when patients exhibit new neurological deficits after placement of a continuous lumbar cerebrospinal fluid drain.

Refractory Primary Vitreoretinal Lymphoma Involving the Spinal Cord with a Temporary Complete Response to Tirabrutinib.

Many patients with primary vitreoretinal lymphoma (PVRL) exhibit central nervous system (CNS) involvement either at the diagnosis or during follow-up. The prognosis in the patients of PVRL with relapsed or refractory CNS remains extremely poor. We herein report a patient with refractory PVRL who had recurrence in the spinal cord despite receiving high-dose methotrexate-based chemotherapy and whole-brain radiotherapy. The patient surprisingly responded to tirabrutinib temporarily. We believe that this case suggests the utility of this new target therapy.

Novel Dural-Splitting Operative Technique for Excision of Ventrally Located Spinal Meningiomas.

OBJECTIVE: Spinal meningiomas are one of the frequently seen intradural extramedullary spinal tumors. They are almost always World Health Organization grade I, and a complete removal of the tumor can be curative. However, ventrally located spinal meningioma removal can be challenging due to the position in front of the spinal cord through a narrow corridor provided by routine dorsal approaches. Incomplete excision of the relatively inaccessible dural attachment can consequently lead to recurrence. We describe a safe and reproducible technique used to achieve Simpson grade I removal of ventrally located spinal meningioma. METHODS: Since the spinal dura can be easily divided into inner and outer layers and the tumor usually spares the outer layer, we developed a simple technique to achieve total resection of the tumor and involved dura while leaving the outer dural layer intact. RESULTS: An advantage of this procedure is that it exploits an interdural approach to allow early devascularization of the tumor without cord manipulation and provides access to the ventral dura to achieve Simpson grade I excision. Another advantage is complete dural closure to minimize postoperative cerebrospinal fluid leak or ventral cord herniation without the need for dural substitutes. CONCLUSION: Its novel interdural approach can be used for all ages and all spinal meningiomas.

Late orbital metastasis from colon cancer complicated by multiple tumors in the breast, lung, liver, and spine.

A 69-year-old woman sustained progressive proptosis for 2 months. The patient had undergone surgery for resection of colon cancer 10 years prior, which was considered to have been completely cured 5 years prior. She was also aware of a hard mass in her left breast, but it had been left untreated. Furthermore, she experienced back pain for a month. Blood examination revealed an elevated level of serum carcinoembryonic antigen, at 17.4 ng/mL (< 5). Computed tomography (CT) revealed a tumor occupying the superolateral part of the right orbit, with intratumoral calcifications and destructive changes in the lateral orbital wall. On magnetic resonance imaging, it appeared as a heterogeneously enhancing, extraconal tumor, 44 mm × 31 mm in maximal dimension, extending into the middle fossa and the adjacent subcutaneous region. Fluorodeoxyglucose positron emission tomography/CT revealed abnormal accumulation in the left breast, T12 vertebra, liver, and lung, in addition to the orbital tumor. The patient underwent total tumor resection through a lateral orbitotomy. Histological examination of the tumor was highly suggestive of a metastatic colon cancer. Late metastasis should be assumed as a differential diagnosis that can be determined only through histological verification.

A large cystic meningioma incidentally detected during general examination for breast cancer.

A 57-year-old woman who underwent needle biopsy for a subcutaneous mass in the breast was diagnosed with invasive ductal carcinoma. General examination incidentally revealed an intracranial tumor. At presentation, the patient showed memory disturbance but no focal neurological deficits. Cranial computed tomography (CT) revealed a large, hypodense cyst in the left frontotemporal region, involving a tumor with extensive hyperostotic changes in the left sphenoid and frontal bones. Magnetic resonance imaging showed that the tumor was attached to the dura mater of the pterional region and extensively enhanced, with involvement of the frontal and sphenoid bones. The less vascular tumor was removed en bloc by drilling the affected sphenoid and frontal bones as much as possible. The microscopic findings of the tumor were consistent with meningothelial meningioma with invasion into the dura mater and bone. Cystic meningioma should be considered when encountered with a dural-based cystic tumor, even in patients with cancer. In such circumstances, prompt and preferential resection may be indicated for intracranial tumors for timely initiation of the long-term treatment of cancer.

Simultaneous presentation of subcortical hemorrhage, subdural hemorrhage, and cerebral infarct in a hemiplegic patient.

A 90-year-old, non-hypertensive woman presented gait disturbance followed by falls. She had developed a lacunar infarction in the right frontal lobe 1 month previously that subsequently resulted in subtle motor weakness in the left lower extremity. At presentation, the patient showed motor weakness in the left upper and lower extremities with normal findings on blood test. Cranial computed tomography (CT) revealed a subcortical hemorrhage in the anterior part of the right frontal lobe that was accompanied by perilesional edema. In addition, two small subdural hematomas, apparently in the acute phase, were found. Magnetic resonance imaging performed immediately after the CT revealed hyperacute infarct in the right precentral gyrus adjacent to the previous infarct. It was hyperintense on the diffusion-weighted imaging but indistinct on the fluid-attenuated inversion recovery sequence. In addition, findings suggesting cerebral contusions were not observed. Based on these, we assumed that the patient's symptoms were mainly derived from the infarct and the subdural hemorrhages had developed in association with falls. However, it was unclear whether the infarct had developed before or after the formation of subcortical hemorrhage. Traumatic and non-traumatic intracranial hemorrhage and cerebral infarcts may present simultaneously. When intracranial hemorrhages appearing on CT do not adequately explain the patient's neurological findings, undetected cerebral ischemia should be assumed.

Delayed traumatic intracerebral hemorrhage associated with dolichoectasia of the middle cerebral artery.

A 74-year-old man tripped while walking. He had not been administered antiplatelet or anticoagulation therapy. At presentation, the patient was well-oriented, with a blood pressure of 130/91 mmHg, while present with tetraplegia and numbness in the upper extremities. Blood work revealed normal findings, while magnetic resonance imaging of the cervical spine revealed severe cord compression at the C3/4 and C4/5 levels. Cranial computed tomography (CT) showed elongated masses in the Sylvian fissures without intracranial hemorrhage. CT taken 2 days later revealed an intraparenchymal hemorrhage located mainly in the right putaminal region, while the patient showed no signs of neurological deterioration. Three-dimensional CT angiography (3D CTA) demonstrated marked ectasia and elongation in the right internal carotid, bilateral middle cerebral, and left anterior cerebral arteries. The patient was conservatively managed. Repeat 3D CTA performed 3 months later showed no de novo abnormalities in the ectatic cerebral arteries. It is assumed that the delayed traumatic intracerebral hemorrhage was caused by disruption of the perforating vessels arising from the ipsilateral dolichoectatic middle cerebral artery. Periodical surveillance neuroimaging is recommended for patients with head trauma who are simultaneously diagnosed with incidental dolichoectasia, especially when complicated with cervical cord injury.

Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway.

Quadrigeminal cistern arachnoid cyst as a probable cause of hemifacial spasm.

Arachnoid cysts arising in the quadrigeminal cistern (ACQCs) are uncommon. A 68-year-old woman presented with an unsteady gait, facial spasm, and cerebellar ataxia. Non-contrast head computed tomography showed a cystic mass centered in the quadrigeminal cistern accompanying ventriculomegaly. On MRI, the cyst appeared hypointense on T1- and hyperintense on T2-weighted sequence. There was no restricted diffusion on diffusion-weighted imaging. The cerebral aqueduct was obstructed and the prepontine cistern was narrowed. The left vertebral artery (VA) coursed adjacent to the facial nerve at its origin. The patient underwent neuroendoscopic fenestration of the posterior wall of the third ventricle and ventral wall of the ACQC. Postoperatively, the patient's symptoms resolved. MRI showed a considerable reduction in the ACQC and expansion of the prepontine cistern, whereas the relationship between the left VA and the proximal segment of the facial nerve did not change. We assumed that the pre-existing close relationship between the VA and facial nerve might have been aggravated by the anterior displacement of the brainstem, thus causing the facial spasm.

An unprecedented case of penetrating head trauma caused by shoji (a Japanese-style paper sliding door).

Penetrating head trauma (PHT) includes any traumatic injury where an object pierces the skull and breaches the dural membrane surrounding the brain. PHTs are less prevalent than blunt head injuries. However, they often have more complex damage, worse prognosis, and higher rates of morbidity and mortality. An 83-year-old man fell at his home and hit his head on the right side toward a shoji (a Japanese-style paper sliding door). He reported to the emergency room the following day with his family. He had a small wound before the right ear, which was sutured in the emergency room. A CT scan demonstrated tiny pieces of bone fragments inside the brain, as well as right temporal subcortical hemorrhage and pneumocephalus. He was admitted to the hospital and received intensive prophylaxis with antibiotics. He developed life-threatening skin disease and subsequent acute kidney disease requiring hemodialysis. He fully recovered from his life-threatening condition. Here, we report an unprecedented case of a penetrating head injury of an older adult caused by a shoji.

Infantile acute subdural hemorrhage probably caused by injury to the diploic channels.

A 6-month-old, previously healthy boy hit the right frontal region of his head against the corner of a plastic toy box. At presentation, a small area with scalp discoloration was noted in the right frontal region. Head computed tomography at the level of discoloration revealed an intracranial hematoma, 5 mm in maximal thickness, below the coronal suture. In addition, there were bony bridges connecting the frontal and parietal bones. Furthermore, a linear crack was found in the diploe of the frontal bone in contact with the coronal suture. Cerebral MRI confirmed linear hyperintensity between the inner tables. We assumed that a kind of ping-pong ball fracture was caused by the head blow, centering on the coronal suture, resulting in rupture of contacting diploic channels and tear of the dura mater, and forming a subdural hematoma. Acute subdural hemorrhage may be caused by an insignificant blow to the coronal suture in infantile patients with underdeveloped cranial bones and sutures, accompanied by subtle external findings.

Supratentorial extraventricular ependymoma presenting calvarial erosion: A report of 3 cases.

Calvarial erosion is an infrequent manifestation associated with oligodendrogliomas, astrocytomas, dysembryoplastic neuroepithelial tumors, astroblastomas, glioblastomas, and meningiomas. Anaplastic ependymoma (AE), a rare malignant form of ependymoma, commonly results in poor prognosis. During the last 12 years, six patients were diagnosed with supratentorial ependymomas. All of them were AEs with extraventricular location identified in the right parietal, left parietal, and left frontal lobes, respectively. Three of them, 7-, 15, and 17-year-old male patients, presented focal calvarial erosion with smooth contour. Calvarial erosion may be a diagnostic hallmark of supratentorial AEs.

An infantile case of posterior fossa arachnoid cyst presenting with marked engorgement of contralateral supraorbital vein.

A 6-month-old, previously healthy boy presented with poor feeding and vomiting for 2 weeks. At presentation, his left supraorbital vein was found to engorge considerably. A cranial computed tomography (CT) scan revealed a large cyst in the posterior fossa with a prominent left superior ophthalmic vein (SOV). Magnetic resonance imaging delineated the well-demarcated cyst markedly compressing the right cerebellar hemisphere. The patient underwent microscopic fenestration of the cyst wall through lateral suboccipital craniotomy. The cyst wall, comprising multi-layered, opacified membranes, was extensively resected and communicated with the prepontine cistern. The histological appearance of the cyst wall was consistent with an arachnoid cyst. Engorgement of the left supraorbital vein resolved immediately after surgery. A postoperative CT scan did not identify the SOV in the left orbit. In the present case, engorgement of the supraorbital vein might reflect the increased venous pressure of the SOV caused by compression of the contralateral cerebellar hemisphere.

Dural arteriovenous fistula with crista galli erosion in a patient with suspected sinusitis.

Dural arteriovenous fistula (dAVF) of the anterior cranial fossa is an aggressive entity with a high risk of intracranial hemorrhage. A 38-year-old woman presented to our institution with nasal obstruction and discharge. Computed tomography (CT) scans performed for suspected sinusitis revealed erosion of the crista galli predominantly on the left side. The frontal and ethmoidal sinuses adjacent to the crista galli were clear and did not communicate with the crista galli. Contrast computed tomography scans revealed ectatic vessels adjacent to the crista galli, coursing on the cortical surface. Cerebral angiography identified an anterior fossa dAVF supplied by the bilateral anterior and posterior ethmoidal arteries and drained by the dilated cortical veins. Based on these findings, we assumed that long-term compression by the pulsatile draining veins caused the erosion. The patient underwent successful microsurgical disconnection procedure of the dAVF with an uneventful postoperative course. We concluded that external erosion of the crista galli could be a sign of aggressive dAVF and requires careful examination.

Mucoepidermoid carcinoma of the lacrimal gland in a patient with the CRTC1-MAML2 fusion gene.

Mucoepidermoid carcinoma (MEC) of the lacrimal gland (LG) is a rare entity. A 47-year-old woman was aware of periorbital swelling for 3 months. At presentation, the patient showed periorbital swelling in the right eye. CT scan showed an isodense mass in the anterior superolateral part of the orbit. MRI delineated the mass as enhancing, extra-conal tumor appearing isointense on T1-weighted sequences, and to be of mixed intensity on T2-weighted sequences. The tumor was totally resected. Microscopically, the tumor tissue was comprised of squamous, epithelioid cells, and cells with plump and clear cytoplasm. Necrosis, neural invasion, or mitotic figures were not observed. Immunohistochemical examination revealed intense staining for cytokeratin 7. A subset of the cells was positively stained with periodic acid-Schiff and mucicarmine stains. Genetic analysis revealed the presence of the CRTC1-MAML2 fusion. The CRTC1-MAML2 fusion may be a useful indicator for the prognosis and planning of adjuvant therapy.

Modeling human brain tumors in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets.

For decades, cell biologists and cancer researchers have taken advantage of non-murine species to increase our understanding of the molecular processes that drive normal cell and tissue development, and when perturbed, cause cancer. The advent of whole-genome sequencing has revealed the high genetic homology of these organisms to humans. Seminal studies in non-murine organisms such as Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio identified many of the signaling pathways involved in cancer. Studies in these organisms offer distinct advantages over mammalian cell or murine systems. Compared to murine models, these three species have shorter lifespans, are less resource intense, and are amenable to high-throughput drug and RNA interference screening to test a myriad of promising drugs against novel targets. In this review, we introduce species-specific breeding strategies, highlight the advantages of modeling brain tumors in each non-mammalian species, and underscore the successes attributed to scientific investigation using these models. We conclude with an optimistic proposal that discoveries in the fields of cancer research, and in particular neuro-oncology, may be expedited using these powerful screening tools and strategies.