Multiple intracranial melanoma metastases: case report and review of the literature.

Although intracerebral metastases of malignant melanoma are common, those located in the sellar region and within the pontocerebellar area are extremely rare. Furthermore, to our knowledge, there is no report about melanoma metastasis to the epiphysis published so far. We report here a 46-year-old patient who had metastatic lesions in the sellar region, cerebellopontine area and epiphysial gland, preceded by a primary melanoma at her left shoulder. The diagnosis of sellar metastasis was confirmed histopathologically following a stereotactic biopsy. The patient received whole-brain irradiation therapy combined with chemotherapy. After 10 months, she died from a severe hemorrhage in the cerebellopontine angle. Autopsy findings confirmed melanoma metastases both in the cerebellopontine angle and additionally in the epiphysial gland. To our knowledge, this is the first case of multiple intracranial melanoma metastases including the suprasellar region, the pontocerebellar and epiphysial area.

Neurosurgical treatment strategies in childhood craniopharyngiomas: is less more?

OBJECTIVE: Craniopharyngiomas in children are typically present in combination with heterogeneous clinical and neuroradiological findings. It has remained highly challenging to choose the optimal treatment strategy with regard to local tumor control and clinical outcome. Here, we analyze different treatment methods and evaluate the results. METHODS: We performed a detailed retrospective evaluation of 32 children <18 years old treated for craniopharyngioma between 1990 and 2008 at the University Hospital Freiburg. Three patient groups could be identified: children treated with microsurgical resection (n=17), with stereotactic cyst drainage and radiotherapy (n=7), and with various combined approaches (n=8). RESULTS: Six of seven children treated with stereotactic cyst punction and radiation are still alive. All of them are in an age-appropriate neuropsychological condition. Two of seven patients in this group have tumor recurrences. Fourteen of the 17 children treated with microsurgical resection show tumor recurrences (p=0.02). Fifteen are alive, and ten out of 17 show an age-appropriate neuropsychological development. The 8.5 years freedom from progression differed from 24% in the resection group to 71% in the cohort treated with stereotactic cyst drainage and radiotherapy (p=0.05). In the third group treated with various approaches, three of eight patients were treated for cystic recurrence. The average follow-up is 5.5 years. CONCLUSIONS: Based on our nonrandomized retrospective monocentric analysis, patients treated with less invasive stereotactic and radiotherapeutical methods have a more favorable long-term clinical outcome compared to children treated with a more radical microsurgical approach. Due to the possible implications of these results, further prospective trials should be encouraged.

High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system.

Thirteen patients (age 38-67 years) with primary lymphoma of the central nervous system (CNS) were treated with methotrexate and cytarabine/thiotepa induction-chemotherapy followed by high-dose carmustine/thiotepa and autologous stem-cell transplantation. Radiotherapy was restricted to patients who did not respond completely to chemotherapy. With a median follow up of 25 months, 3-year DFS and OS was 77%.

Subthalamotomy in cervical dystonia: A case study of lesion location and clinical outcome.

Here we report a 63-year-old woman with primary cervical dystonia (CD) whose symptoms subsided for more than 30 years following a unilateral stereotactic subthalamotomy contralateral to the overactive left sternocleidomastoid muscle but then gradually recurred over a period of several months. The aim of the present study was to correlate the topography of the stereotactic lesion with the long lasting therapeutic effect. High-resolution magnetic resonance imaging and subsequent stereotactic analysis were performed to determine the anatomical localization of the lesion. The primary coagulation focus comprised the posterior subthalamic white matter in the prelemniscal radiation and field H of Forel. Neighboring structures were implicated to various extents. It is suggested that the posterior subthalamic area, with its abundance of interconnecting fibers and related nuclei, represents an effective target for the neurosurgical treatment of CD that may be explored further with deep brain stimulation.

Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker?

PURPOSE: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy. EXPERIMENTAL DESIGN: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification. RESULTS: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender. CONCLUSIONS: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.

Subthalamic nucleus deep brain stimulation in elderly patients--analysis of outcome and complications.

BACKGROUND: There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. METHODS: Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age > or = 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. RESULTS: Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. CONCLUSION: DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate.

Treatment options for gelastic epilepsy due to hypothalamic hamartoma: interstitial radiosurgery.

Surgical treatment of hypothalamic hamartomas (HHs) as the underlying etiology of gelastic epilepsy is associated with a high risk of complications because of the close vicinity of adjacent structures such as the optic tracts and mammillary bodies. Treatment with interstitial radiosurgery uses stereotactically implanted (125)I seeds emitting gamma radiation from the center of the lesion, with a steep spatial gradient, over a period of about 3 weeks. This form of HH therapy offers particular advantages regarding the risk for major side effects. In a series of 15 children and adolescents treated in Freiburg, Germany, 53% of patients achieved significant improvement in seizure frequency (Engel class I or II outcome). Transient side effects were related to the development of local edema, resulting in headache and mental slowing. A persistent weight gain was noted in 3 patients, which was severe in 1 (20 kg). There were no other neurologic, neuropsychologic, or neuropsychiatric side effects, which compares favorably with most surgical series.

Long-term survival in patients with brain metastases.

PURPOSE: The aims of this study are: (a) to determine long-term survival in patients with brain metastases who underwent whole brain radiation therapy; (b) to evaluate whether long-term survival can be predicted by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA); and (c) to review the literature on long-term survival. MATERIAL AND METHODS: The records of 916 patients with brain metastases who underwent whole brain radiation therapy at our hospital from 1985 to 2000 were analyzed retrospectively. RESULTS: By July 2001, 891 patients had died. Median survival of the whole group was 3.4 months. Overall survival was 5.6% at 2 years (at risk: n=48), 2.9% at 3 years ( n=25), 1.8% at 5 years ( n=12), and <1% at 10 years ( n=1). Survival for 2 years or more was observed in RTOG RPA class 1, but also in class 2 patients. Within both classes, survival was significantly better for patients with a single brain metastasis compared with those patients having multiple metastases. A survey of the literature revealed that in rare instances survival of 10 years or more was seen in patients with brain metastases. The majority of these patients had a single brain metastasis treated by radical resection and whole brain radiation therapy. CONCLUSION: Even in patients with favorable characteristics, survival for 2 years or more after the diagnosis of brain metastases is considerably low. Aggressive therapy in RPA class 1 and class 2 patients with a single brain metastasis occasionally permits long-term survival.

Long term course of WHO grade II astrocytomas of the Insula of Reil after I-125 interstitial irradiation.

OBJECTIVE: To present long-term results after interstitial iodine-125 irradiation of adult patients with de-novo World Health Organization (WHO) Grade II astrocytomas and oligoastrocytomas of the insula of Reil with special respect to the treatment-related risk. METHODS: 55 consecutively treated patients (from 1979 to 1992) with circumscribed tumors with a diameter < 5 cm (astrocytomas: 46 patients, oligoastrocytomas: 9 patients) were included. The reference dose-calculated to the outer boundary of the tumor-was in the range of 60-100 Gy and the dose rate was low (< 10 cGy/h). Progression-free survival, risk of malignant transformation, survival, and the incidence of radiogenic complications were estimated by the Kaplan-Meier method. Prognostic factors were obtained from the Cox-model. RESULTS: Median follow up for the survivors was > 10 years. 5-year (10-year) progression-free survival was 40.7 % (20.2 %), and 5-year (10-year) survival 54.6 % (28.4 %). Malignant transformation occurred in 42.4 % after 5 years. Neither of the Kaplan-Meier curves showed a leveling off over time. Transient (progressive) radiogenic complications were observed in 13 [4] patients (one-year overall complication rate: 18%), and were significantly associated with a tumor diameter >3.5 cm (p<0.001). No long term side-effects were detected and delayed external beam irradiation (in case of tumor progression) did not enhance the risk. Tumor enhancement on CT was the only unfavorable predictor for survival. CONCLUSION: A limited overall prognosis for adult patients with insular WHO grade II astrocytomas and oligoastrocytomas was detected. Interstitial I-125 irradiation offers a minimal-invasive and low-risk treatment option for circumscribed tumors with a diameter < 3.5 cm. Larger tumors require further evaluation for optimal treatment.

Radiosurgery followed by planned observation in patients with one to three brain metastases.

OBJECTIVE: To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS: A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS: Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION: Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

Malignant pineal parenchymal tumors in adult patients: patterns of care and prognostic factors.

OBJECTIVE: The aim of our study was to analyze patterns of care and to identify prognostic factors in patients at least 18 years of age who received radiotherapy for malignant pineal parenchymal tumors. METHODS: In a multicenter, retrospective study, we analyzed data for 37 previously published cases and 64 patients treated at the participating institutions. RESULTS: A total of 56 patients received postoperative radiotherapy, and 45 patients received primary radiotherapy. Chemotherapy was administered to 34 patients. The median follow-up period was 38 months, and median overall survival was 100 months. The variables that significantly influenced overall survival were the extent of disease (localized versus disseminated; P = 0.0002), differentiation (pineal parenchymal tumor of intermediate differentiation versus pineoblastoma; P = 0.001), and residual disease (> or = 50% versus < 50% reduction in size; P < 0.0001). In a multivariate analysis, the parameters turned out to be independent risk factors. The median survival in patients with local or spinal failure was 15 months. Local control was better in older patients (> or = 32 yr versus < 32 yr; P = 0.02). Spinal control was more successful in patients with pineal parenchymal tumors of intermediate differentiation than it was in patients with pineoblastomas (P = 0.03). Nine of 45 treatment failures occurred later than 5 years after treatment. CONCLUSION: Stage, histological characteristics, and response are independent risk factors in adults with malignant pineal parenchymal tumors. Late relapses are common.

Deep brain stimulation of the nucleus ventralis intermedius for Holmes (rubral) tremor and associated dystonia caused by upper brainstem lesions. Report of two cases.

Holmes tremor is caused by structural lesions in the perirubral area of the midbrain. Patients often present with associated symptoms such as dystonia and paresis, which are usually refractory to medical therapy. Here, the authors describe two patients in whom both tremor and associated dystonia improved markedly following unilateral stimulation of the thalamic nucleus ventralis intermedius.

Incidental stereotactic diagnosis of cerebral insults.

Among the patients (6854 patients 1990-1999) who underwent computer-assisted stereotactic biopsy most were referred with the presumptive diagnosis of a brain mass lesion. Forty-three cases (0.63%) were found in which the final histopathological diagnosis excluded a neoplastic, infectious or inflammatory lesion but disclosed a cerebral insult. Histologically these could be subdivided into ischemic insults in 38 cases (88%) and hemorrhagic insults in five cases (12%). On the basis of clinical and radiological findings in this group, 35 patients (81%) were sent to our department because of suspected neoplasmatic lesions, two patients (5%) because of multiple sclerosis, two patients (5%) because of inflammatory disease and one patient (2%) because of a suspected infectious parasitic disease. All patients underwent initial CT examinations which showed hypodense lesions of the brain in 38 patients (88%) and hyperdense lesions in five cases (12%). Constant enhancement on CT scans of the mass lesion was found in 12 patients (28%) only. Fourteen lesions (33%) were located in the right hemisphere, five lesions (12%) in the left hemisphere, nine lesions (21%) in the basal ganglia, four lesions (9%) in the midbrain, two lesions (4.5%) in the corpus callosum and one lesion (2%) in a thalamus. Multiple lesions were present in eight cases (19%). The most common initial neurological symptoms upon clinical presentation were hemiparesis (18 patients, 42%), epilepsy (eight patients, 18%), a change in mental status (six patients, 14%). There was no mortality and no operative morbidity associated with the stereotactic biopsy in this group of patients. The most common neurological disorder, cerebrovascular insult, rarely poses diagnostic problems. If there are doubts a serial stereotactic biopsy can safely clarify the situation.

Nystagmus in suprasellar tumors: recent advances in diagnosis and therapy.

Congenital and acquired nystagmus, particularly pendular and jerk nystagmus, see-saw nystagmus and spasmus nutans, may be the presenting sign of a suprasellar mass lesion.(1) The large variety of different suprasellar mass lesions requiring quite different therapeutic measures necessitates exact histological diagnosis for optimal therapeutic strategy planning.(2) Stereotactic tumor biopsy has become a well-established diagnostic approach, combining minimal surgical trauma with a high degree of diagnostic safety. Particularly in the two most frequent suprasellar mass lesions - craniopharyngiomas and pilocytic astrocytomas - accurately planned stereotactic drainage of tumor cysts combined with radiotherapy and/or stereotactic radiosurgery allows successful decompression and tumor control as well as maximum preservation of visual and endocrinological functions when compared with conventional surgical procedures.(2-11)

Quo vadis, academia? Can academic neurosurgery be resurrected?

Clinical neurosurgery is an endangered academic discipline. Neurosurgeons have competition from many directions: orthopedists, ear, nose and throat surgeons, plastic surgeons, radio-oncologists, and interventional radiologists, among others. Academic centers are no longer the only sites of neurosurgical education at the attending level, and neurosurgery is not felt to be an indispensible part of an undergraduate medical curriculum. There are insufficient data to determine if neurosurgical services for the general population are adequate or appropriate. The traditional strengths of academic neurosurgery are gathering data, analysis, research, innovation, and teaching within a context of understanding and tradition. Future healthy development of neurosurgery ideally requires multidisciplinary teams in specialized referral centers. When this consideration is combined with the existing shortage of neurosurgeons across the country, academic neurosurgery departments must logically focus on how best to allocate resources between "routine" clinical services and research objectives. We suggest here that new relationships may be required between university centers and community health care providers. Restructuring of the neurosurgical workforce may be necessary if academic neurosurgery is to develop as a specialty of comprehensive expertise in the challenging neurological disease entities that are its research objectives.

Long-term results of brachytherapy with temporary iodine-125 seeds in children with low-grade gliomas.

PURPOSE: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. METHODS AND MATERIALS: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. RESULTS: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. CONCLUSIONS: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.

Stereotactic interstitial radiosurgery with the Photon Radiosurgery System (PRS) for metastatic brain tumors: a prospective single-center clinical trial.

PURPOSE: To evaluate the efficacy and the treatment outcome of tumor patients being treated stereotactically with a miniature X-ray generator (Photon Radiosurgery System, PRS). METHODS AND MATERIALS: Thirty-five patients with histologically diagnosed cerebral metastases were treated with a single fraction of stereotactic interstitial irradiation (median, 18 Gy). Clinical and neuroimaging evaluation were assessed at 2-, 6-, and 12-week intervals postoperatively and every 3 months thereafter. Survival, local control, and distant and overall brain freedom from progression were obtained using the Kaplan-Meier method. RESULTS: Median survival was 7.37 months and the actuarial survival rates at 6 and 12 months were 60.0% and 34.3%, respectively. Acute complications on six patients were associated with shorter survival. Local tumor control at the initial stage and at the last follow-up were 82% and 50%. Eighteen patients (53%) developed distant brain metastases after treatment. At 1 year, the local control rate and distant and overall brain freedom from progression were 33.0%, 43.3%, and 14.7%, respectively. A shorter local tumor control was observed by PRS treatment of a recurrent tumor and by irregular tumor configuration. CONCLUSIONS: Interstitial radiosurgery with the PRS requires continued investigation. It allows for an immediate and potentially cost-efficient treatment for patients with singular, small (

Radiosurgery followed by planned observation in patients with one to three brain metastases.

OBJECTIVE: To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS: A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS: Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION: Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.