Long-term outcome of deep brain stimulation in generalised dystonia: a series of 60 cases.

BACKGROUND: There is solid evidence of the long term efficacy of deep brain stimulation of the globus pallidus pars interna in the treatment of generalised dystonia. However there are conflicting reports concerning whether certain subgroups gain more benefit from treatment than others. We analysed the results of a series of 60 cases to evaluate the effects of previously proposed prognostic factors including dystonia aetiology, dystonia phenotype, age at onset of dystonia, and duration of dystonia prior to treatment. METHODS: 60 patients with medically intractable primary or secondary generalised dystonia were treated with deep brain stimulation of the globus pallidus pars interna during the period 1999-2010 at the Department of Neurosurgery in Oxford, UK. Patients were assessed using the Burke-Fahn-Marsden (BFM) Dystonia Rating Scale prior to surgery, 6 months after implantation and thereafter at 1 year, 2 years and 5 years follow-up. RESULTS: The group showed mean improvements in the BFM severity and disability scores of 43% and 27%, respectively, by 6 months, and this was sustained. The results in 11 patients with DYT gene mutations were significantly better than in non-genetic primary cases. The results in 12 patients with secondary dystonia were not as good as those seen in non-genetic primary cases but there remained a significant beneficial effect. Age of onset of dystonia, duration of disease prior to surgery, and myoclonic versus torsional disease phenotype had no significant effect on outcome. CONCLUSIONS: The aetiology of dystonia was the sole factor predicting a better or poorer outcome from globus pallidus pars interna stimulation in this series of patients with generalised dystonia. However even the secondary cases that responded the least well had a substantial reduction in BFM scores compared with preoperative clinical assessments, and these patients should still be considered for deep brain stimulation.

Paraplegia due to drop metastases from anaplastic oligodendroglioma.

In this article, we report on a rare case of spinal seeding from a cerebral anaplastic oligodendroglioma presenting with signs of medullar compression. We discuss the prevalence, mechanisms and imaging findings of spinal seeding in various gliomas. A suitable clinical treatment and follow up for these patients is suggested.

Development of neuromodulation treatments in a large animal model--do neurosurgeons dream of electric pigs?

The Göttingen minipig has been established as a translational research animal for neurological and neurosurgical disorders. This animal has a large gyrencephalic brain suited for examination at sufficient resolution with conventional clinical scanning modalities. The large brain, further, allows use of standard neurosurgical techniques and can accommodate clinical neuromodulatory devises such as deep brain stimulation (DBS) electrodes and encapsulated cell biodelivery devices making the animal ideal for basic scientific studies on neuromodulation mechanisms and preclinical tests of new neuromodulation technology for human use. The use of the Göttingen minipig is economical and does not have the concerns of the public associated with the experimental use of primates, cats, and dogs, thus providing a cost-effective research model for translation of rodent data before clinical trials are initiated.

Neuromodulation in a minipig MPTP model of Parkinson disease.

Large animal neuroscience enables the use of conventional clinical brain imagers and the direct use and testing of surgical procedures and equipment from the human clinic. The greater complexity of the large animal brain additionally enables a more direct translation to human brain function in health and disease. Economical, ethical, scientific and practical issues may on the other hand hamper large animal neuroscience. Large animal neuroscience should therefore either be performed in order to examine large animal species dependent problems or to complement promising small animal basic studies by constituting an intermediate research system, bridging small animal CNS research to the human CNS. We have, accordingly, during the last ten years used the Gottingen minipig to examine neuromodulatory treatment modalities such as stem cell transplantation and deep brain stimulation directed towards Parkinson disease. This has been accomplished by the development of a MPTP-based large animal model of Parkinson disease in the Gottingen minipig and the development of stereotaxic and surgical approaches needed to manipulate the Gottingen minipig CNS. The instituted changes in the CNS can be evaluated in the live animal by brain imaging (PET and MR), cystometry, gait analysis, neurological evaluation and by post mortem examination based on histology and stereological analysis.

Does chronic low-dose treatment with cyclosporine influence the brain? A histopathological study in pigs.

Twenty percent of the patients immunosuppressed with cyclosporine A (CsA) develop neurological side effects such as tremor, paresthesias, headache, seizures, visual disorders, paresis, and coma-CsA encephalopathy. The encephalopathy resolves on CsA discharge; autopsies of recovered patients are normal. Characteristic lesions are seen on magnetic resonance imaging (MRI) during the period of encephalopathy. MRI of asymptomatic patients receiving CsA as well as most recovered patients are normal. Several theories of pathogenesis have been proposed, but none has been firmly established. The current placebo-controlled study, blinded to the investigator, was accordingly initiated to elucidate histopathological changes in the brain. Twelve adult Göttingen minipigs were randomized into two groups treated with either low-dose CsA (10 mg/kg/d) or no treatment for 6 months. Behavior, blood pressure, and blood parameters were measured throughout the study. All animals had a cerebral MRI before sacrifice. Three control pigs and one CsA-treated pig died during observation and were excluded from the study. None of the remaining eight pigs displayed behavioral signs or MRI-visible lesions characteristic of CsA encephalopathy. The brains appeared all normal on the gross pathological examination, but microscopy revealed perivascular, meningeal, and neuronal tissue infiltration with granulocytes and mononuclear cells in one CsA-treated pig, while the remaining pigs were without histopathological lesions. Pathological changes were noticed in one out of five CsA-treated animals, corresponding to the percentage of patients treated with CsA who develop CsA encephalopathy. To pursue this finding, two studies, one using CsA 20 mg/kg/d for 6 months and one using CsA 10 mg/kg/d for 12 months, have been initiated.

Pulsed dose rate (PDR) brachytherapy as salvage treatment of locally advanced or recurrent gynecologic cancer.

PURPOSE: Pulsed dose rate (PDR) brachytherapy is a new treatment option permitting dose distribution optimization in interstitial implants. It possesses the advantage of equipment simplification and radiation protection to the staff, compared to the manually afterloading technique. This study presents the first clinical results from The Finsen Center with PDR-brachytherapy in patients with locally advanced or recurrent gynecologic cancer. METHODS AND MATERIALS: Between June 1993 and August 1996, 34 patients with gynecologic malignancies (22 pelvic recurrences, 12 primary locally advanced) have been treated with external irradiation, four-field box technique, to 46 Gy/23 fractions, 5 F/week and 192Ir-interstitial PDR-brachytherapy in pulses of 0.6 Gy, one pulse per hour to a total of 30 Gy. The Martinez Universal Perineal Interstitial Template applicator was used for all implantations. RESULTS: The overall complete response rate was 74%. At median 14 months follow-up (range 3-40) 15 patients were alive with no evidence of disease. Seven of 14 patients with a second recurrence or progressive disease were still alive. The overall 1- and 2-year survival was 71% and 63%, respectively. There was no difference in survival probability when stratifying the patients by primary diagnosis (recurrent vs. primary advanced), relapse locations (central vs. central + pelvic wall mass) or treatment volume. Seventeen chronic grade III complications were observed in 10 patients. Large treatment volumes significantly correlated to severe gastrointestinal complications. Fifteen of 17 chronic grade III complications were observed in patients treated for recurrent disease. CONCLUSION: PDR-brachytherapy in combination with external irradiation is an effective treatment option for patients with locally advanced or recurrent gynecologic cancer, although substantial toxicity is observed in patients with large treatment volumes and recurrent disease.

Pulsed dose rate (PDR) brachytherapy of anal carcinoma.

BACKGROUND AND PURPOSE: With radiotherapy of anal carcinomas, sphincter preservation can be obtained at survival rates similar to those obtained with radical surgery. By combining external beam irradiation with interstitial irradiation, superiority over standard external irradiation has been obtained. With the introduction of pulsed dose rate equipment, where a single high activity source moves through catheters, a more individualized dose distribution and a further elimination of radiation exposure to the staff can be achieved. MATERIALS AND METHODS: Between June 1993 and November 1994, 17 patients with anal carcinoma (T1:4, T2:4, T3:6, T4:3) have been treated at the Finsen Center. The treatment consisted of three-field external irradiation 46 Gy/23 fractions with five fractions a week to the anal canal and regional pelvic lymph nodes. Seven to 33 days after completion of external irradiation, the tumorspace was given 25.2 Gy PDR brachytherapy with 42 pulses of 0.6 Gy, one pulse every hour. RESULTS: One isolated local recurrence has been noted 13 weeks after implantation. One additional local recurrence was seen in a patient with concomitant hepatic and inguinal recurrence. In three patients inguinal recurrence had occurred, two of these patients were irradiated without any further evidence of disease, and one patient with a primary advanced tumour, had local failure. So far necrosis has been observed in 13 patients within 1-49 weeks (median 16 weeks) after implantation. Eight of these patients required colostomy. No relation was observed between the number of implanted needles and the occurrence of necrosis. CONCLUSIONS: The results indicate that the treatment is highly effective, but with substantial toxicity.