Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology

G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas β-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of β-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of β-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or β-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or β-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.

Microbleeds in Patients with Primary Intracerebral Hemorrhages

OBJECTIVE: We investigate risk factors of cerebral microbleeds(MBs) and their relation to concomitant magnetic resonance (MR) findings in intracerebral hemorrhages(ICHs) patients. METHODS: We studied 100 consecutive patients with primary ICH over a 1-year period. These patients underwent brain MR images using 3.0-T scanners within the first week of the hemorrhage. MBs and old hematomas were located and counted by using T2*-weighted gradient-echo MR imaging. We also counted lacunes and graded white matter and periventricular hyperintensity on T1- and T2-weighted spin-echo sequences. The association between MBs and vascular risk factors and MR abnormalities were analyzed. RESULTS: MBs were seen in 77 of ICH patients, and their number ranged from 1 to 65 lesions (mean 11, median 6). The locations of MBs were subcortex-cortex (40.6%), basal ganglia (26.7%), thalamus (14.1%), brain stem (12.5%), and cerebellum (9.1%). Analysis of clinical data revealed that age, hypertension, history of stroke, and duration of hypertension were frequently associated with MBs. The incidence of lacunes, old hematomas, and advanced leukoaraiosis was significantly higher in the MBs group, compared with the patients without MBs. CONCLUSION: MBs are frequently observed in ICH patients with advancing age, chronic hypertension, and previous hemorrhagic stroke, and are also closely related with morphological signs of occlusive type microangiopathy, such as lacunar infarct and severe leukoaraiosis.

Treatment of Scalp Arteriovenous Malformation

OBJECTIVE: The object of this study is to present the treatment experience of the 6cases of scalp arteriovenous malformations(AVMs) focus on treatment strategy. METHODS: Six patients with scalp AVM were treated during past 12years. We analysis the clinical characteristics of the lesions, treatment methods and management outcomes. RESULTS: The lesions were located on temporal in 2 patients, parietal in 2 patients, frontal and occipital area in each one. Four of six patients had a trauma history on scalp. The presenting symptoms were progressive enlarged pulsating mass with or without bruit. Four of the six lesions had the large fistula in the lesion. Two patients were treated with surgical resection alone, three patients with proximal feeding artery balloon(s) occlusion followed by surgical resection, and one patient with coil embolization through trans-venous route alone. We obtained good results in all patients. CONCLUSION: Most of scalp AVM can be completely cured by judicious selection and a combination of treatment modalities, i.e., surgery only, or embolization only, or embolization plus surgical therapy. Although embolization became a primary therapy for this sort of scalp AVM recently, the selection of treatment modality should be chose based on the size, angioarchitecture, and clinical presentations of the lesion.

Treatment of Supratentorial Primitive Neuroectodermal Tumors (PNETs) in Children

OBJECTIVE: Strategies for managing supratentorial primitive neuroectodermal tumors(PNETs) in children include surgical resection, craniospinal irradiation and chemotherapy. This study is performed in order to compare the efficacy of various methods of treatment and to describe its optimal management. METHODS: We have reviewed all medical records and pathology slides of six children(four males and two females) with supratentorial PNET from November, 1987 to May, 2003. The extent of resection was confirmed by computed tomography and magnetic resonance studies. RESULTS: The patients were aged 1 to 13 years and treated postoperatively with/without adjuvant therapy. Tumor location included was four cortical, one gangliobasal, and one pineal region. The presenting symptoms and signs consisted of increased intracranial pressure and focal neurological deficits such as seizure and hemiparesis. The treatment consisted of surgical resection alone in one patient, postoperative radiotherapy in one patient, postoperative chemotherapy in one, and postoperative radiotherapy with chemotherapy in three. Five patients lived more than 12 months after diagnosis and one patient among them has been living more than 5 years after diagnosis. CONCLUSION: We can improve the survival and prognosis of supratentorial PNET patients by radical gross total resection of tumor followed by craniospinal irradiation and aggressive chemotherapy. First of all, gross total resection of tumor is the most important among many factors.

Ictal SPECT-guided Epilepsy Surgery in a Patient with Forme Fruste Tuberous Sclerosis

Tuberous sclerosis is an autosomal dominant disease characterised by hamartomas (tubers) in many organ systems and the four major intracranial manifestations including cortical tubers, white matter abnormalities, subependymal nodules and subependymal giant cell astrocytoma. But there is immense variability in the clinical presentation of tuberous sclerosis and many incomplete forms (formes frustes) exist. Almost all patients with tuberous sclerosis have seizures and mental retardation. The authors experienced a 7-year-old boy with medically intractable epilepsy without any skin lesion or mental retardation. In terms of surgical standpoint for determination of extent of resection, corticectomy on the overriding cortex of right premotor and lesionectomy of periventricular calcified lesion were performed according to ictal single photon emission computed tomography(SPECT), which showed hyperperfusion in the subcortical and calcified area. Histopathologic findings showed a few cytologically abnormal neurons with extensive gliosis, containing many Rosenthal fibers, reactive astrocytes and dense calcification, composing of abundant calcospherites which suggested forme fruste tuberous sclerosis. During the follow-up period of eighteen months, seizure was free after surgery.

Craniopharyngioma in the Temporal Lobe: A Case Report

Herein, we report on an unusual case of craniopharyngioma arising in the temporal lobe with no prior history of surgery and with no connection to the craniopharyngeal duct. MR images showed a cystic tumor with a small solid portion. To the best of our knowledge, this is the first case of a craniopharyngioma occurring in the temporal lobe.

Treatment for Recurrent Cerebral Aneurysm

OBJECTIVE: The aim of this study is to make a management strategy for the patients with recurrent cerebral aneurysm after surgery. METHODS: Over a 19-year period, 1, 546 patients were treated for a ruptured intracranial aneurysm surgically. Twenty-six of these patients(1.7%) were subsequently treated for regrowing aneurysm(8) or de novo aneurysm formation(26). Among them, twenty-three individuals who presented with recurrent subarachnoid hemorrhage underwent conventional angiography to detect the aneurysm recurrence. Three-dimensional computed tomographic angiography was performed in the remaining three patients who complained chronic headache. The mean age at the first surgery was 48.6 years. An interval ranging from 1 to 192 months(mean, 76.1 months) since the original treatment. RESULTS: Total 34 recurrent aneurysms in 26 patients were treated by microsurgical clipping(29 cases), wrapping(1 case), and endovascular coiling(4 cases) as a second procedure. A satisfactory outcomes were achieved in twenty-one patients(80.8%) during a mean 69.5 months follow-up period. The most common site of the recurrence was the internal carotid-posterior communicating artery. Patients with de novo aneurysms are frequently hypertensive(61.1%) and younger in age(55.6%). CONCLUSION: The treatment of recurrent cerebral aneurysm could be performed effectively using direct operations and/or endovascular procedures.

Enhanced Focus in Hypertensive Intracerebral Hematoma on CT Scan and Hematoma Enlargement / 대한뇌혈관외과학회지

OBJECTIVE: Although most of hypertensive intracerebral hematoma (HICH) are static after ictus, a minority of them can enlarge in the acute phase after onset. This study performs to find the predicting factors and signs of hematoma enlargement in patients with HICH. METHODS: Among 140 cases of HICH treated during 1.5 years, the authors selected 107 cases who underwent contrast enhanced and nonenhanced initial CT scanning within 12 hours after symptom onset and a follow-up CT scan in order to investigate the enlargement of hematoma. Those cases were divided into two groups:hematoma enlargement (group I) and non-enlargement group (group II). The comparison of predicting factors (bleeding tendency, abnormal liver function and blood pressure) and signs (enhanced focus in hematoma on CT) of hematoma enlargement between group I and II was performed. RESULTS: There were 8 cases in group I and 99 cases in group II. The incidence of an enhanced focus in hematoma on CT scan was higher in group I than group II (87.5% vs. 9.1%, p<0.05). The systolic blood pressure (BP) at 6 hours after symptom onset and at the time of the first CT scan was higher in group I than group II (172.5 vs. 152.0 mm Hg, and 182.5 vs. 158.6 mm Hg, respectively, p<0.05). There was no difference in the incidence of bleeding tendency and abnormal liver function between group I and II. CONCLUSION: Contrast enhanced brain CT scan to detect the enhanced focus in the hematoma is one of useful methods to predict the early enlargement of hematoma in patients with HICH. The continuance of a high BP in spite of medication of antihypertensive drugs during the acute period after the onset of symptoms is another predictive sign of hematoma enlargement in patients with HICH.

Current Indications of Surgery and Endovascular Treatment in Ischemic Stroke / 대한뇌혈관학회지

OBJECTIVE: To know the indications and logics of surgical and endovascualar treatment for patients with carotid stenosis. METHODS: The surgical indications and logics of symptomatic and asymptomatic carotid stenosis, and indication of angioplasty and stenting for carotid stenosis are discussed with the review of literatures. RESULTS: Carotid endarterectomy is indicated in patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter and patients with symptomatic (recent transient ischemic attacks or nondisabling strokes) high-grade carotid stenosis (70 to 99%) with or without contralateral carotid stenosis or occlusion. The angioplasty and stenting for carotid stenosis may be indicated in patients who have the significant medical comorbidity, recurrent high-grade stenosis after endarterectomy, contralateral carotid occlusion, radiation induced stenosis, surgically difficult to access high-cervical stenosis and tandem lesion. CONCLUSION: Neurologists who have the primary management role for the cerebral ischemic patient in our country should be familiar with the surgical indications of carotid stenosis. They should try to find the patients who need the carotid endarterectomy and recommend them to surgeon to have the surgery. The cooperation among neurologist, neuroradiologist, vascular surgeon and neurosurgeon will improve the management results of patients with cerebral ischemic disease.

Treatment of Langerhans Cell Histiocytosis of Head and Neck

OBJECTIVE: The author presents a retrospective analysis of 11 patients with Langerhans cell histiocytosis (LCH) of head and neck to describe its optimal treatment strategies. METHODS: This study involved five male and six female patients with a median age of 11 years. Sites of involvement included calvarium(9 cases), temporal bone(1 case), and cervical node(1 case). Ten patients had a solitary symptomatic lesion in the time of presentation. The localized LCH of calvarium(eosinophilic granuloma) was treated by surgery alone(8 cases) or surgery plus radiotherapy(1 case). An infant presented with multifocal disease received systemic chemotherapy. The patient who had extensive temporomastoid lesion with aural mass underwent radical mastoidectomy and cranial irradiation due to incomplete resection. RESULTS: The time from initial symptom to diagnosis ranged from 10 days to four months(mean, 54 days). In cases with calvarial involvement, a painful lump with tenderness was the most common symptom at admission and a typical punched out lesion was seen on skull radiographs. No recurrence of symptoms or relapse of radiological evidence was observed during follow up, except for one infant who died of progressive multisystemic LCH. CONCLUSION: It is suggested that complete surgical excision is the treatment of choice for unifocal cranial LCH, leaving radiotherapy for possible relapse. Systemic chemotherapy can also plays an important role in the control of more extensive diseases in children.

Treatment of Epilepsies Associated with Cerebral Infarction in Childhood

OBJECTIVE: The authors present experience of treatment on the patients who suffered from epileptic seizures with ischemic stroke in their childhood. METHODS: We reviewed the clinical characteristics, neuroimaging findings, and electroencephalographic records of thirteen patients who suffered from seizures with stroke in childhood. Ten patients were improved to be seizure-free or to fall into only rare seizures with appropriate anticonvulsant medication. Three of these patients showed medical intractability in spite of appropriate multi-drug therapy, so they were carefully evaluated to consider the candidate for epilepsy surgery based on our sophisticated presurgical studies. Surgical intervention was performed in these selected 3 cases according to intracranial recordings with subdural grids, who had focal electroencephalographic abnormalities in diffuse cortical lesions. RESULTS: The series included 8 women and 5 men with ages at seizure onset ranging from 3 to 38 years (mean 14.3 years). Cerebral ischemia was caused by various life threatening early insults including febrile convulsion, difficult delivery, viral meningoencephalitis, near drowning, and severe dehydration. Simple partial seizure with or without secondary generalization was most commonly noted. Magnetic resonance image revealed a wide variation in size, shape, and location of the infarcted areas. Major vascular territory and watershed area infarction involving diffuse cerebral cortex was a powerful cause of post-stroke seizure. Excellent clinical result was achieved even in the patients who underwent surgery. CONCLUSION: Control of late onset seizures related to childhood cerebral infarction is not a trivial one, because of its wide, sometimes multilobar territories. However, enthusiastic medical trial as well as comprehensive surgical consideration is essential for better seizure control related to quality of life.

Results of Computed Tomography-guided Stereotactic Biopsy for Intracerebral Mass Lesions

OBJECTIVE: The diagnostic results are analyzed in a consecutive 55 patients undergoing computerized tomography(CT)-guided stereotactic brain biopsies. METHODS: There were 32 males and 23 females, and their mean age was 44.9(range 8 to 74) years. The biopsy procedure was generally carried out under local anesthesia. Three to four specimens were obtained with side-biting biopsy needles or cup biopsy forceps, usually from the enhancing portion or central hypodense area within the lesion. In 41 patients of brain tumor, 61% had frozen section guidance intraoperatively. The accuracy of targeting by postoperative CT scan was 95%. RESULTS: The lesions identified were neoplastic disease in 41 cases(75%), vascular disease in three, and infectious process in two. Forty-six cases revealed a definitive diagnosis, and 9 cases(16%) were classified as nondiagnostic. The stereotactic biopsy modified the clinical presumptive diagnosis in fifteen patients(28%), with changing the treatment modality. The final diagnosis was achieved in 8 of 9 failed biopsy patients based on the results from craniotomy(1), second biopsy(3), cerebrospinal fluid study(2), and clinical monitoring(2). The positive biopsy rate was 85% for brain tumors. In 10 cases of brain tumor, the histological studies from biopsied materials and resection tissue were identical. Comparison between the frozen section diagnosis and the final diagnosis based on the permanent sections revealed that they matched in 23(92%) cases. Five patients experienced transient neurological worsening after stereotactic biopsy. CONCLUSION: The representative tissue sampling and intraoperative assessment of sample quality by frozen section examinations can improve the diagnostic yield for the stereotactic brain biopsy. In a small number of patients who had inconclusive results, issues on repeating stereotactic biopsy or open biopsy, clinical and radiological follow-up, or choosing empiric therapy should carefully be considered.

Transnasal Repair of Traumatic Cerebrospinal Fluid Rhinorrhea

OBJECTIVE: This study is aimed to evaluate the efficacy of transnasal repair of cerebrospinal fluid(CSF) rhinorrhea. METHODS: Thirteen patients with traumatic noniatrogenic CSF fistulas were included in the retrospective analysis. High-resolution thin-section computed tomographic cisternography was helpful in localization of the CSF leakage site. The most frequent leakage site was the sphenoid sinus. The transnasal approach(TNA), comprised of endonasal endoscopic surgery(EES) or transseptosphenoidal surgery(TSS), was mainly used for smaller fistulas. Total or selected ethmoidectomy depended on the localization of the leakage. Wide sphenoidotomy enabled detection and repair of CSF leaks from the sphenoid cavity. Three patients also underwent transcranial approach(TCA) because of the large or multi-fragmented bony defect and the need for further exposure for repair. Five patients developed ascending meningitis in the preoperative period with antibiotic prophylaxis. RESULTS: Twenty-five leaks were initially repaired using one of three techniques:EES alone in eight patients, EES plus TCA in three, and TSS alone in two. Ten patients who solely underwent the TNA did not experience the complications of the traditional TCA. One recurrent sphenoid fistula was successfully treated by TSS. After a follow-up from 12 to 88 months(mean 32.7), the overall success rate for 25 CSF fistulas was 100%. CONCLUSION: The transnasal repair is a safe, successful, and alternative approach for the surgical repair of traumatic CSF rhinorrhea, and also could be combined to TCA.

The Outcome of Transsphenoidal Microsurgery for Acromegaly

OBJECTIVE: The authors present a retrospective clinical analysis of transsphenoidal surgery for acromegaly including preoperative factors determining the therapeutic outcome. METHODS: Forty-three patients(24 females, mean age 45.3 years) harboring growth hormone(GH)-secreting adenomas(13 microadenomas and 30 macroadenomas) were treated between the years 1987 and 2001. The mean duration of follow-up was 69 months. RESULTS: The average estimated duration of symptoms prior to diagnosis was 8 years. The control rate following surgery was 51%(22 out of 43 cases). Of the patients with postoperative persistent disease, 11 patients had had additional bromocriptine therapy with or without irradiation, and consequently 7 patients achieved biochemical remission. The overall remission rate of multimodality treatment was 67%. The preoperative GH value, tumor size, extrasellar extension of tumor, the number of surgeons, and the extent of the surgical removal were significant univariative predictors of outcome(p<0.05). CONCLUSION: This study suggests that surgical outcome for acromegaly could be achieved by a experienced neurosurgeon. In the group of the patients of large or invasive adenomas, with the less probability of surgical control, adjunctive medical or radiation therapy to control GH hypersecretion should be considered.

Rebleeding of Cerebral Aneurysm during Three-Dimensional Computerized Tomographic Angiography

The authors report a 59-year-old woman who presented with diffuse subarachnoid hemorrhage and focal intracerebral hemorrhage in the right frontotemporal region with intraventricular hemorrhage after the right middle cerebral artery bifurcation aneurysmal rupture. The aneurysm was rebled during the 3-dimensional computerized tomographic angiography, which was performed 3 hours after initial attack. Although the aneurysm was successfully clipped, the patient died on the second hospital day. We discuss the risk factor of rebleeding of ruptured cerebral aneurysm and whether 3-dimensional computerized tomography angiography is a really safe method of detection of cerebral aneurysm in terms of rebleeding.

Alterations of 9p21-22 Region Encoding Genes in Primary Glioblastomas

BACKGROUND: Glioblastomas are one of the most common and aggressive malignant glial tumors occuring in the central nervous system. This study analyzed the status of p15INK4b, p14ARF, p16INK4a, MTAP, IFNA, and IFNB genes in 36 primary glioblastomas to investigate whether the inactivation of these genes participate in primary glioblastoma tumorigenesis. METHODS: We used polymerase chain reaction, polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) analysis, and methylation-specific PCR. RESULTS: Homozygous deletions at the p16INK4a gene were detected in 11 cases (30.5%) of 36 primary glioblastomas, and the promoter hypermethylation was found in 3 cases (8.3%) of 36 primary glioblastomas. In mutational analysis for the p16INK4a gene by PCR/SSCP, there was no abnormal mobility-shifted band in 36 cases of primary glioblastomas. The overall frequency of p16INK4a alterations including homozygous deletion and promoter hypermethylation in 36 primary glioblastomas was 38.8% (14 of 36). Deletions of p15INK4b were noted in 4 cases (11.1%), whereas deletions of the p14ARF and MTAP genes were detected in 1 case of 36 cases of primary glioblastomas. But deletions of the INFA and B genes were not found. CONCLUSIONS: These results suggest that alterations of the p16INK4a gene can be important mechanisms of the tumorigenesis of primary glioblastomas, and the p16INK4a gene is inactivated by mechanisms including homozygous deletion and promoter hypermethylation.

Management of Chiasmatic-Hypothalamic Gliomas in Children

OBJECTIVE: Management strategies for pediatric chiasmatic-hypothalamic gliomas(CHG) include surgery, irradiation, chemotherapy and a combination of these modalities. This study was performed in order to compare the efficacy of various methods of treatment and to describe its optimal management. MATERIAL AND METHOD: We have reviewed the results of management of 6 children with a diagnosis of CHG, who were observed closely during the last 8 years. The patients were aged 7 months to 15 years. Our patients presented with diencephalic syndrome, endocrine dysfunction, and progressive visual loss. None of these had evidence of neurofibromatosis-1. Treatment consisted of surgery alone(2), surgry and irradiation(2), surgery, irradiation and chemotherapy(1), and surgery and chemotherapy(1). RESULTS: Four children had large exophytic suprasellar tumors and two showed diffuse midline lesions. Obstructive hydrocephalus was present in all patients. Pathologic examination revealed anaplastic astrocytoma in 1 and low-grade astrocytoma in 5. Two patients, recently treated with radiation therapy following radical subtotal resection, showed significant tumor reductions and good clinical status. Four patients had partial tumor resection. Of these patients, two developed disease stabilization during follow-up period of 7 and 8 years, respectively. Life-threatening complications were noted in remaining two patients. CONCLUSION: CHG may follow an unpredicatable course and show a various reponse to each treatment modality. Further studies are indicated to define the optimal method of treatment of CHG in childhood.

The Value of MRI in Diagnosis of Peripheral Nerve Disorders

OBJECTIVE: The development of magnetic resonance neurography(MRN) has made it possible to produce high-resolution images of peripheral nerves themselves, as well as associated intraneural and extraneural lesions. We evaluated the clinical application and utility of high-resolution MRN techniques for the diagnosis and treatment of a variety of peripheral nerve disorder(PND)s. MATERIAL AND METHOD: MRN images were obtained using T1-weighted spin echo, T2-weighted fast spin echo with fat suppression, and short tau inversion recovery(STIR) fast spin-echo pulse sequences. Fifteen patients were studied, three with brachial plexus tumors, five with chronic entrapment syndromes, and seven with traumatic peripheral lesions. Ten patients underwent surgery. RESULTS: In MRN with STIR sequences of axial and coronal imagings, signals of the peripheral nerves with various lesions were detected as fairly bright signals and were discerned from signals of the uninvolved nerves. Increased signal with proximal swelling and distal flattening of the median nerve were seen in all patients of carpal tunnel syndrome. Among the eight patients with brachial plexus injury or tumors, T2-weighted MRN showed increased signal intensity in involved roots in five, enhanced mass lesions in three, and traumatic pseudomeningocele in three. Other associated MRI findings were adjacent bony signal change, neuroma, root adhesion and denervated muscle atophy with signal change. CONCLUSION: MRN with high-resolution imaging can be useful in the preoperative evaluation and surgical planning in patients with peripheral nerve lesions.

Treatment Strategies for Primary Central Nervous System Lymphoma

OBJECTIVES: We have currently changed treatment strategies to methotrexate(MTX)-based preirradiation chemotherapy with subsequent planned radiation for the initial therapy of primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the results of treating PCNSL with chemotherapy plus radiotherapy (CRT) or radiotherapy(RT) alone. METHOD ADN MATERIAL:This study involved 10 females and 3 males patients with a mean age of 54.2 years. All patients underwent surgery, open(8 cases) or stereotactic biopsy(5 cases) for histological diagnosis. Eleven tumors were diffuse large B-cell lymphomas. Tumor volume change in the follow-up images and survival time were evaluated in patients treated with CRT and RT alone. In the beginning, two patients received ProMACE-Cytabom chemotherapeutic regimen, but did not complete the course and died of progressive tumor 8 and 9 months after diagnosis, respectively. One patient died at 6 months before chemotherapy. These three were excluded from the survival analysis. Five patients(RT group) completed full courses of cranial irradiation with or without boost. For the current combined modality treatment, high-dose MTX-based chemotherapy(systemic and intrathecal MTX, IV vincristine, and oral procarbazine) followed by whole brain irrdiation to 45Gy to tumor was introduced in 5 patients of CRT group. RESULT: A complete response was achieved in three of five who received RT only and in all of five who received CRT. All patients in CRT groups are in disease free status at a mean 23 months following therapy. The RT group patients refused any additional salvage therapy at tumor relapse and survived at mean 20 months from diagnosis. The Karnofsky performance status improved in eight of ten patients with treatment. The treatment toxicity included leukoencephalopathy in RT group and severe leukopenia, transient hepatitis, avascular necrosis of femoral head, hearing loss, and amenorrhea in CRT group, respectively. CONCLUSION: The combined modality therapy of MTX-based chemotherapy plus radiotherapy for PCNSL may enhance tumor response and improve patient survival. The patients who received CRT should be carefully followed up because of the higher risk of treatment-induced late neurotoxicity.

Vestibular Schwannoma with Malignant Transformation: A Case Report

We describe a rare case of malignant transformation in a vestibular schwannoma in a 33-yr-old woman. She presented herself with headache, tinnitus, and hearing loss and underwent posterior fossa explorations three times during the short period of 3 months. The clinicopathological features of the original tumor were typical of benign vestibular schwannoma. Despite a comlpete microsurgical excision, two months later, the tumor recurred locally with a rapid increase in size causing a progressive worsening of neurological symptoms. A diagnosis of malignant schwannoma was made for the recurrent tumor on the basis of the microscopic findings of high cellularity, moderate pleomorphism, and the presence of mitotic cells. Repeat magnetic resonance imaging performed a month after the second surgery unexpectedly showed definite tumor enlargement. She remained clinically stable following the third debulking of the tumor and adjuvant radiotherapy. We propose that this recurrent tumor represent malignant transformation from a benign vestibular schwannoma which was an unusual occurrence in a patient without neurofibromatosis.