Takamitsu Fujimaki

Central nervous system germ cell tumors: classification, clinical features, and treatment with a historical overview.

Central nervous system germ cell tumors are neoplasms that affect children and young adults. They are subclassified into germinoma and nongerminomatous germ cell tumors. The latter include teratoma (mature teratoma, immature teratoma, teratoma with malignant transformation), choriocarcinoma, embryonal carcinoma, yolk sac tumors, and mixtures of these entities. Germinoma with syncytiotrophoblastic giant cells is a variant of germinoma. Germinomas respond well to radiation therapy, but late sequelae due to irradiation have been reported. The results of radiation treatment alone for nongerminomatous germ cell tumor are not satisfactory. Combination radiochemotherapy has been applied, and this yields a good outcome with less toxicity for germinomas and better survival of nongerminomatous germ cell tumors. This article also discusses other issues, including the controversy regarding spinal irradiation and the treatment of recurrent disease.

Repetitive Transcranial Magnetic Stimulation Once a Week Induces Sustainable Long-Term Relief of Central Poststroke Pain

Central poststroke pain is a serious problem for some patients after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been reported to relieve poststroke pain but its efficacy is still controversial. We tested the possibility that rTMS, when applied once a week, would induce sustainable relief of poststroke pain.

Preoperative assessment of hemifacial spasm by the coronal heavily T2-weighted MR cisternography.

BackgroundMicrovascular decompression (MVD) has become a well-established surgical procedure for hemifacial spasm (HFS). Before surgery, it is essential to evaluate any possible deformity of the brainstem and establish the precise location of the offending vessels. In the present study of HFS patients we examined coronal sections taken by heavily T2-weighted MR cisternography in addition to routine axial sections, and assessed the usefulness of these images through comparison with intraoperative findings.MethodsEighty patients with HFS underwent preoperative coronal heavily T2-weighted MR cisternography before microvascular decompression surgery. Three neurosurgeons examined the preoperative axial and coronal MR images and evaluated vessel invagination into the brainstem. The usefulness of coronal sections was assessed statistically by the Mann-Whitney U test.ResultsInvagination of the offending vessel into the brainstem was observed in 24 cases (30.0%). In 19 patients, it was predicted preoperatively that compression of the flocculus and brainstem would be required in order to approach the offending vessels. Coronal MR cisternography was significantly more useful in cases with vessel invagination into the brainstem than in cases without invagination.ConclusionsCoronal sections obtained by MR cisternography are able to demonstrate the severity of vessel invagination into the brainstem as well as revealing the presence of the offending vessel. This information is helpful for planning a suitable approach to the root exit zone.

Combination Therapy with Rituximab and Temozolomide for Recurrent and Refractory Primary Central Nervous System Lymphoma

High-dose methotrexate-based chemotherapy has extended survival in patients with primary central nervous system lymphoma (PCNSL). However, although salvage treatment is necessary in recurrent and refractory PCNSL, this has not been standardized. We herein describe the efficacy of a combination of rituximab and temozolomide (TMZ) in two consecutive patients with recurrent and refractory PCNSL. Based on the immunohistochemical study, case 1 had a non-germinal center B-cell-like (non-GCB) subtype, was positive for bcl-2 and negative for O6-methylguanine-DNA methyltransferase (MGMT). Case 2 was GCB subtype, bcl-2-, and MGMT+. Because of the positive expression of MGMT, interferon-beta was additionally given in case 2. Complete responses and partial responses were obtained after the third and fourth cycles of combination therapy, respectively. This was maintained for 12 months, with acceptable toxicity. The combination of rituximab and TMZ was effective in tumors with different immunohistochemical profiles. This combination therapy warrants further study in a larger population.

Disappearance of gadolinium enhancement in a chemoresistant astrocytoma of the tectum after high-dose interferon beta.

Interferon beta 6 million units per week was administered to a patient with an aggressive astrocytoma in the tectum that was resistant to cisplatin, etoposide, vinblastine, and the oral alkylating agent temozolomide. The tumor was immunopositive for O6-methylguanine-DNA methyltransferase (MGMT). Interferon beta caused the disappearance of the gadolinium-enhanced lesion in the tectum. Interferons have apoptotic and antiangiogenic effects on tumor cells, and the lesions disappearance may have been induced by complexes of these effects. Administration of interferon beta might have a favorable effect on tectal gliomas that are immunopositive for MGMT and resistant to chemoradiotherapy including temozolomide.

Does arteriosclerosis contribute to hemifacial spasm

BackgroundHemifacial spasm (HFS) is caused by pulsative vascular compression of the root exit zone (REZ) of the facial nerve. However, the mechanism that causes the offending vessels to compress the REZ has not been clarified. Elongation of intracranial arteries due to arteriosclerosis is one possibility, but such arteriosclerotic changes are not observed very frequently among patients with HFS. The aim of the present study was to investigate whether arteriosclerotic changes would contribute to the pathogenesis of HFS.MethodsThis study included 111 HFS patients, all of whom were Japanese. The prevalence rates of hypertension, hyperlipidemia, and diabetes mellitus were examined as risk factors of atherosclerosis, and the cardio-ankle vascular index (CAVI) was measured as an indicator of arteriosclerotic change. The severity of white matter lesions (WMLs) in HFS patients was measured by magnetic resonance imaging. These data were compared with data from healthy Japanese controls.ResultsThe prevalence rates of the risk factors for atherosclerosis in the HFS patients were not higher than those in the general Japanese population. The CAVI scores for the HFS patients were similar to, or lower than those in the healthy controls for all age groups except 60 to 69-year-old men. The severity of WMLs in the HFS patients was not significantly worse than that in the controls.ConclusionsIt is suggested that arteriosclerotic changes are not involved in the pathogenesis of HFS, and that vascular compression syndromes are attributable to anatomical features of the intracranial arteries and facial nerves formed during the prenatal stage.

Successful Treatment of Hemifacial Spasm Caused by an Ectatic Vertebral Artery Accompanying Agenesis of the Carotid Artery

We report the successful treatment of a patient with hemifacial spasm due to a tortuous vertebral artery that appeared to have developed to compensate for agenesis of the ipsilateral carotid artery. The 51-year-old man presented with a 1-year history of progressive left hemifacial spasm. His medical history was otherwise unremarkable except for untreated mild hypertension. Magnetic resonance angiography and bone window computed tomography demonstrated congenital agenesis of the left carotid artery and compression of the root exit zone of the left facial nerve by a tortuous left vertebral artery (VA). Microvascular decompression was performed via a left suboccipital craniotomy, and the offending vessel was identified using endoscopy. The vertebral artery was successfully transposed using polytetrafluoroethylene (PTFE) tape and a PTFE ball (Bard PTFE felt, Tempe, Arizona). This is the first report of a patient with hemifacial spasm caused by an ectatic VA associated with agenesis of the ipsilateral carotid artery.

Changes in intracortical inhibition and clinical symptoms after STN-DBS in Parkinson’s disease

OBJECTIVES To examine effects of subthalamic nucleus deep brain stimulation (STN-DBS) on intracortical inhibition in Parkinsons disease (PD) and the correlation between intracortical inhibition and clinical symptoms after alteration of STN-DBS status. METHODS Nine PD patients treated by STN-DBS were compared with eight age-matched controls. Antiparkinsonian medication was withdrawn 12h before the study. Short-interval intracortical inhibition (SICI) with a 3-ms interval and silent period (SP) were examined using transcranial magnetic stimulation. SP duration, SICI and motor symptoms (rigidity and tremor) were evaluated with STN-DBS ON, and over 120 min during STN-DBS OFF. RESULTS Even during STN-DBS, PD patients showed a shortened SP and reduced SICI relative to normal controls. SICI decreased further throughout STN-DBS OFF, resulting in facilitation rather than inhibition; SP shortened only after 120 min STN-DBS OFF. Both rigidity and tremor worsened throughout STN-DBS OFF, with a time course similar to SICI. CONCLUSION Even during STN-DBS, both SICI and SP in PD patients remain impaired without medication. Changes in SICI, but not SP, show a time course similar to those of motor symptoms. SIGNIFICANCE The dissimilarity of SICI and SP changes suggests differences in mediation of inhibitory mechanisms and/or superimposition of exaggerated intracortical facilitation on SICI.

Malignant transformation of germinoma 14 years after onset: Favorable efficacy of oral etoposide.

We report the case of a 19‐year‐old woman with a highly malignant intracranial germ cell tumor (GCT) that developed 14 years after treatment for neurohypophyseal germinoma. Magnetic resonance imaging (MRI) showed a large neurohypophyseal mass and a synchronous lesion in the pineal region. Plasma α‐fetoprotein was elevated to 3038 ng/mL. Although the tumor shrank and tumor marker levels normalized after chemotherapy and craniospinal irradiation, treatment was switched to oral etoposide for the residual tumor because of adverse events. MRI after oral etoposide introduction showed additional tumor shrinkage for 27 months after the onset of the second tumor. To the best of our knowledge, this is the longest interval between germinoma onset and the development of highly malignant recurrent GCT to be reported in the English‐language literature. Oral etoposide prevented regrowth of the GCT, which has a poor prognosis, and decreased the size of the residual tumor.

Central Nervous System Germ Cell Tumor

Central nervous system germ cell tumors (CNSGCTs) are tumors of children and young adults. They affect mainly the pineal body, neurohypophysis (“suprasellar” area) and basal ganglia, but can arise in any other CNS location. Histologically, they are divided into germinoma and non-germinomatous germ cell tumors (NGGCTs), the latter including teratoma, embryonal carcinoma, choriocarcinoma, and yolk sac tumor. Teratomas are further subclassified into mature teratoma, immature teratoma, and teratoma with malignant transformation. Except for mature teratoma, all of these tumors are biologically malignant. Histologically, they resemble reproductive cells, fetal tissues, or related tissues such as placenta, and mixtures of these tumor subcategories are not rare. Initial symptoms include increased intracranial pressure due to obstructive hydrocephalus, abnormality of ocular movement and endocrine disorders. Some tumors of these subclasses produce humoral tumor markers, beta-human chorionic gonadotropin, alpha-fetoprotein or other markers, which can be used for differential diagnosis or clinical follow-up. Only mature teratoma can be cured with surgery alone, and the other tumors require adjuvant therapy for complete remission. Germinomas respond well to irradiation and can be cured, but platinum-based chemotherapy combined with reduced-dose irradiation has been recently used to minimize radiation-related toxicities or complications. As the other tumors cannot be cured by irradiation alone, more intensive platinum-based chemotherapy and radiation therapy including whole-neuroaxis irradiation are employed. Although better disease control and longer survival can now be achieved, the results of treatment are still not satisfactory. Therefore, development of new treatments, and improvements to existing ones, are needed for CNSGCTs.