F. Dubois

Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions. During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation (weekly frequency of attacks decrease >50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Clinical outcomes after Gamma Knife surgery for idiopathic trigeminal neuralgia: review of 76 consecutive cases

OBJECT Stereotactic radiosurgery is an increasingly used, and the least invasive, surgical option for patients with trigeminal neuralgia (TN). In this study, the authors performed a retrospective evaluation of the safety and efficacy of this method for idiopathic TN. METHODS The authors reviewed data from 76 patients with idiopathic TN who underwent Gamma Knife surgery (GKS). The mean age of the patients was 64 years (range 27-83 years). All patients had typical features of TN. Thirty patients (39.5%) had previously undergone surgery. The intervention consisted of GKS on the retrogasserian cisternal portion of the fifth cranial nerve. The mean maximum GKS dose used was 85.1 Gy (range 75-90 Gy). RESULTS Patients were followed-up from 6 to 42 months (mean 20.3 months) after GKS. Complete pain relief was achieved in 83.1% of the patients within 1 year, 70.9% within 2 years, and 62.5% within 3 years. Patients who underwent previous surgery demonstrated a lower rate of pain relief (p < 0.05). Twenty patients (26.3%) reported pain recurrence between 6 and 42 months after treatment. New or worsened persistent trigeminal dysfunction developed after GKS in 16 patients (21%); 8 of these patients described some facial numbness/not bothersome, and 8 reported some facial numbness/somewhat bothersome. None of the patients developed troublesome dysesthesia or anesthesia dolorosa. CONCLUSIONS Gamma Knife surgery for idiopathic TN proved to be safe and effective and was associated with a particularly low rate of complications.

99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent, primary brain tumors.

BackgroundMalignant brain tumors carry a pejorative prognosis and necessitate aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With limited response rate and potential toxicity to chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. AimTo define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy response in recurrent primary brain tumors. MethodsIn a retrospective analysis, thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT system. A MIBI uptake index (UI) was computed as the ratio of counts in the lesion to those in contralateral region. For all patients, we compared changes over time in UI with MRI and clinical data. ResultsThe changes in UI agreed well with the clinical and MRI-based assessments in 97% of cases. In 44% of these cases, the scintigraphic response appeared before the MRI response. In instances of treatment failure or rebound, the concordance between scintigraphy and MRI was 52%, and the scintigraphic response appeared before the MRI response in 48% of cases. ConclusionThis study confirms our previous results obtained on a short series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT in prediction of chemotherapy response. Moreover, in cases of tumor progression, we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an average 4 months before MRI changes.

Increasing of HER2 membranar density in human glioblastoma U251MG cell line established in a new nude mice model

SummaryGlioblastoma multiform (GBM) remains the most devastating primary tumour in neuro-oncology. Human Epithelial Receptor Type 2 (HER2) is a transmembrane tyrosine/kinase receptor that is important for cancer growth. HER2 is not expressed in adult glial cells, but its expression increases with the degree of astrocytomas anaplasia. We have recently demonstrated the ability of anti-HER2 antibodies to induce in vitro apoptosis GBM cell lines; this ability is correlated to HER2 density. A decreasing of tyrosine/kinase receptors density during in vitro culture was reported. No information exists about the variation of HER2 expression after in vivo implantation. For that, the two cell lines in vitro tested (U251MG, A172) were in vivo implanted. We established a U251MG in vivo model in balb/c nude mice showing an important increasing of HER2 density. The HER2 density is correlated to anti-HER2 antibody efficiency so this model will be useful for the evaluation of in vivo anti-HER2 antibody treatment.

H - 15 Métastases intracérébrales d’un oligodendrogliome anaplasique médullaire

Introduction Les metastases cerebrales secondaires aux gliomes intramedullaires sont rares. Nous rapportons le premier patient presentant des metastases cerebrales histologiquement prouvees d’un oligodendrogliome anaplasique medullaire. Observation (Cas n° SB/04/141) Un patient de 22 ans, traite par chirurgie, radiotherapie et chimiotherapie pour un oligodendrogliome medullaire cervical de grade III, presentait 19 mois plus tard une symptomatologie d’hypertension intracrânienne. L’IRM encephalique montrait 2 lesions rehaussees par le gadolinium, qui n’existaient pas sur l’IRM realisee lors du diagnostic tumoral medullaire initial. Une des lesions etait lateralisee a droite dans le cervelet, a proximite du 4 e ventricule, et l’autre etait localisee dans le plexus choroide droit. On ne trouvait pas de lesions meningees diffuses et l’IRM medullaire ne mettait pas en evidence d’evolutivite de la lesion initiale. Il existait une hyper-proteinorachie (0,96 g/l) associee a une hypercytose (7,2/mm 3 ), mais sans cellules anormales, a la ponction lombaire. Le patient decedait 3 mois plus tard. L’analyse immunohistochimique des prelevements autopsiques confirmait le diagnostic de metastases cerebrales d’un oligodendrogliome anaplasique. L’etude microscopique trouvait une atteinte tumorale des leptomeninges. Discussion Les metastases cerebrales des gliomes medullaires sont probablement secondaires a une dissemination des cellules tumorales, qui peut etre favorisee par le contact de la tumeur avec les voies d’ecoulement du LCR et par les effractions chirurgicales, comme en temoigne la proximite des metastases du systeme ventriculaire, et l’atteinte microscopique des leptomeninges dans notre observation. Conclusion Ce cas suggere un mecanisme de dissemination des cellules tumorales le long des voies de circulation du LCR, qui pourrait etre favorisee par la manipulation chirurgicale.