[Surgical Case of Accidental Infantile Acute Subdural Hematoma Caused by Household Minor Head Trauma:Hyperperfusion during Postoperative Hemispheric Hypodensity, Namely "Big Black Brain"].

We experienced a case of an accidental infantile acute subdural hematoma caused by household minor head trauma(Nakamura type I intracranial hemorrhage)with postoperative hemispheric hypodensity lesion(Big Black Brain)whose pathophysiology was analyzed using perfusion MRI. A ten-month-old boy was admitted to our hospital in a comatose state. His mother revealed that the boy suffered a fall from a sofa bed. A CT scan indicated massive acute subdural hematoma in the left cerebral hemisphere. Emergency craniotomy and hematoma evacuation were performed. On postoperative day 3, CT revealed hemispheric hypodensity, and the boy suffered from status epilepticus. MRI on the following day showed widespread white matter hyperintensity in diffusion-weighted images, and MRA demonstrated dilation of the middle cerebral artery. Perfusion MRI using the dynamic susceptibility contrast method revealed a marked increase in cerebral blood flow in the left hemisphere. These abnormal MRI and MRA findings disappeared on postoperative day 13. Status epilepticus also improved upon administration of multi-antiepileptic drugs. Fundoscopy findings on postoperative day 3 showed small bilateral petechial or brush retinal hemorrhages. However, whole-body examination did not show any problems, and was consistent with the mother's account. Thus, we judged non-abusive head trauma. Although follow-up MRI showed diffuse atrophy of the left cerebral hemisphere, the boy aged well without obvious paresis or verbal developmental delay as judged by a follow-up more than a year later. Based on these results, we speculated that hyperperfusion caused by dilation of the cerebral artery was related to the postoperative hemispheric hypodensity, namely "Big Black Brain".

Polysomnography as an indicator for cervicomedullary decompression to treat foramen magnum stenosis in achondroplasia.

OBJECTIVE: Management of cervicomedullary compression due to foramen magnum stenosis in achondroplasia remains controversial, especially for patients with no symptoms or mild symptoms. We examined the effectiveness of polysomnography (PSG) as an indicator for cervicomedullary decompression treatment. METHODS: We retrospectively reviewed nine achondroplasia cases (mean age 1 year and 9 months) treated from 2008 to 2015. All patients were examined by PSG, magnetic resonance imaging (MRI), and otolaryngeal fibroscopy. We analyzed demographic data, clinical presentation, degree and type of respiratory impairment, severity of foramen magnum stenosis and concomitant cervicomedullary compression, treatment (conservative or surgical), and clinical outcome. RESULTS: Eight of nine patients presented with no severe symptoms in the daytime. However, MRI revealed four severe, four moderate, and one mild case of cervicomedullary compression, and PSG demonstrated severe sleep apnea in four cases and moderate sleep apnea in five cases. All sleep apnea cases were obstructive or obstructive-dominant. Fibroscopy revealed no upper airway stenosis in six cases and mild stenosis in three cases. Four patients who had severe sleep-related respiratory disturbance on PSG and severe or moderate cervicomedullary compression were treated by cervicomedullary decompression. Three of these patients demonstrated improved sleep respiration soon after surgery, while one required temporary tracheostomy due to bilateral vocal cord paralysis caused by compression during intratracheal intubation. CONCLUSION: Polysomnography can be a useful indicator for cervicomedullary decompression surgery, especially in cases of seemingly asymptomatic achondroplasia with severe foramen magnum stenosis.

Third Ventricle Germ Cell Tumor Originating from the Infundibulum with Rapidly Expansive Enlargement.

We present a pediatric case of a rapidly expanding third ventricle germ cell tumor (GCT). A 14-year-old boy suffered from gradual-onset central diabetes insipidus (DI) and received desmopressin treatment. Magnetic resonance imaging (MRI) showed nonspecific findings of the pituitary-hypothalamic axis. Nine months after the initial DI diagnosis, he developed progressively worsening headache. MRI demonstrated a third ventricle tumor causing noncommunicating hydrocephalus, although an MRI 16 weeks before admission did not show the lesion. We performed gross total resection (GTR) of the tumor in 2 stages: a translamina terminalis approach and an extended transsphenoidal approach. The lesion was histologically diagnosed as immature teratoma with some germinoma. His noncommunicating hydrocephalus resolved after surgery. Through postoperative radiochemotherapy (whole ventricle: 23.4 Gy/13 fractions, tumor bed: 27.0 Gy/15 fractions, and 3 courses of carboplatin-etoposide), he has was in complete remission at the 3-year follow-up and has continued his high school program. This case suggests the following: (1) a mixed GCT originating from the neurohypophysis/infundibulum can show rapidly expansive growth in a child with central DI; (2) GTR and adjuvant radiochemotherapy can result in a good therapeutic outcome in rapidly expanding GCT; and (3) the extended transsphenoidal approach is a complementary approach to transcranial resection of anterior third ventricle GCTs.

[Bilateral Internal Carotid Artery Dissection Caused by Elongated Styloid Processes:A Case Report].

We report a case of bilateral internal carotid artery(ICA)dissection associated with bilateral elongated styloid processes(ESPs). A 46-year-old man presented with transient aphasia and left visual disturbance at a business meeting. He complained of a foreign body sensation in his throat during swallowing for two years. Magnetic resonance imaging(MRI)demonstrated fresh small infarcts in the left corona radiata. Magnetic resonance angiography(MRA)revealed string signs bilaterally in the cervical ICAs. The patient was diagnosed with bilateral idiopathic ICA dissection and was treated with ozagrel and clopidogrel. Three-dimensional computed tomographic angiogram(3DCTA)indicated bilateral ESPs and bilateral ICA stenosis. 3DCTA with the patient's head tilting and neck extension revealed that each ICA was compressed by the ipsilateral ESP. A follow-up MRA showed complete normalization of bilateral ICAs after neck rest and anti-platelet therapy, following which, clopidogrel was stopped. The patient wore a soft cervical collar until the operation, to avoid contact between the ESPs and ICAs due to changes in head position. Bilateral ESP resection was performed to prevent recurrence of cerebral ischemic events caused by ICA dissection. The patient was discharged one week after the surgery without any neurological deficit. There was no recurrence of symptoms during the next eight months after the operation.

Perifocal Inflammatory Reaction with Volume Fluctuation Caused by Diagnostic Radiation-Induced Regression in Germinoma Makes Histological Diagnosis Difficult despite Its Disappearance following Treatment: A Significant Pitfall and Countermeasures to It.

We present a pediatric case of neurohypophyseal germinoma with a perifocal inflammatory reaction (PIR) with volume fluctuation caused by diagnostic radiation-induced regression (DRIR). On-target biopsy failed to confirm the histology because PIR hardly contained any germinoma cells. DRIR-related fluctuation of the tumor volume disguised germinoma as inflammation. We analyzed the cerebrospinal fluid (CSF) and detected a high level of placental alkaline phosphatase (PLAP), which demonstrated the neurohypophyseal lesion to be germinoma and brought the patient from successful radiochemotherapy up to complete remission. PIR adjacent to the germinoma (PIRAG) disappeared completely following radiochemotherapy, although it contained almost no germinoma cells. Examination of the CSF-PLAP level can complement the diagnosis of germinoma and will decrease the risk of misdiagnosis. Neurosurgeons should keep in mind PIRAG, DRIR, and the diagnostic value of CSF-PLAP when germinoma is suspected.

Long-term outcomes in patients with pineal nongerminomatous malignant germ cell tumors treated by radical resection during initial treatment combined with adjuvant therapy.

BACKGROUND: For pineal nongerminomatous malignant germ cell tumors (NGMGCTs), we mainly performed radical tumor resection during initial treatment combined with adjuvant therapy. METHODS: We retrospectively analyzed 17 patients treated for pineal NGMGCTs between 1986 and 2007 at the University of Niigata. RESULTS: Twelve patients underwent total or subtotal resection of their tumor via the occipital transtentorial approach. Five patients underwent partial resection, and four of them later underwent total resection by salvage surgery. After surgery, eight patients were treated with combined radiochemotherapy including whole-brain irradiation, two received radiation monotherapy, one had chemotherapy with local irradiation, and six were treated with chemotherapy alone. The median follow-up period for surviving patients was 179 months. The 10-year overall survival and progression-free survival rates for the radiochemotherapy group were both 75.0 % (two patients had a recurrence and died); the rates for other adjuvant therapies were 77.8 % (two died) and 22.2 % (seven had a recurrence), respectively. Radiochemotherapy was significantly associated with an increased rate of progression-free survival compared with the other adjuvant therapies (p = 0.0396). CONCLUSIONS: For pineal NGMGCTs, initial treatment strategies including gross total resection of the tumor before or after whole-brain irradiation and chemotherapy provided good therapeutic outcomes. Obtaining complete remission of the primary tumor, irrespective of the timing of surgical resection (i.e., before or after adjuvant therapies), or complete response by neoadjuvant radiochemotherapy during an initial treatment appears to be essential for improving therapeutic outcomes of intracranial NGMGCTs.

Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma.

Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re-evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation-free (DF) MB. Gli3-immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P < 0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3-IR was observed at the nuclear membrane. The overall survival and event-free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.

Endoscopic biopsies of lesions associated with a thickened pituitary stalk.

BACKGROUND: Lesions associated with a thickened pituitary stalk (TPS lesions) revealed by magnetic resonance imaging have a diverse pathology. Accordingly, for clinical decision-making, it is necessary to make a diagnosis based on histopathological examination of the TPS lesions. The objectives of this study were to review endoscopic biopsies of TPS lesions and to assess the surgical strategy for treating these lesions. METHODS: Eleven patients (four males and seven females) aged from 6 to 75 years underwent endoscopic biopsy of a TPS lesion between 2006 and 2011 at University of Niigata. The relationships of the extent of lesions with surgical approaches were retrospectively examined. RESULTS: Among the 11 patients, a biopsy was performed via an endoscopic transsphenoidal approach for five with intrasellar lesions; via an endoscopic extended transsphenoidal approach for two with localized TPS lesions; and via an endoscopic intraventricular approach for four with the lesion protruding from the infundibulum. Histopathological examinations of all the lesions confirmed diagnoses of germinoma in four patients, hypophysitis in three, Langerhans cell histiocytosis in two, craniopharyngioma in one, and cancer metastasis in one. None of the 11 patients had further deterioration of pituitary function postoperatively. CONCLUSIONS: Endoscopic biopsy of TPS lesions is a less invasive alternative to open biopsy requiring transcranial surgery. The endoscopic transsphenoidal approach is most suitable for biopsies of TPS lesions associated with intrasellar lesions. Otherwise, the endoscopic intraventricular approach seems reasonable for intraventricular lesions protruding from the infundibulum, and the endoscopic extended transsphenoidal approach appears appropriate for localized TPS lesions.

[Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome].

A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome.

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin.

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.