B. Ampe

Single Fraction Versus Fractionated Linac-Based Stereotactic Radiotherapy for Vestibular Schwannoma: A Single-Institution Experience

PURPOSE To evaluate and compare outcomes for patients with vestibular schwannoma (VS) treated in a single institution with linac-based stereotactic radiosurgery (SRS) or by fractionated stereotactic radiotherapy (SRT). METHODS AND MATERIALS One hundred and nineteen patients (SRS = 78, SRT = 41) were treated. For both SRS and SRT, beam shaping is performed by a mini-multileaf collimator. For SRS, a median single dose of 12.5 Gy (range, 11-14 Gy), prescribed to the 80% isodose line encompassing the target, was applied. Of the 42 SRT treatments, 32 treatments consisted of 10 fractions of 3-4 Gy, and 10 patients received 25 sessions of 2 Gy, prescribed to the 100% with the 95% isodose line encompassing the planning target volume. Mean largest tumor diameter was 16.6 mm in the SRS and 24.6 mm in the SRT group. Local tumor control, cranial nerve toxicity, and preservation of useful hearing were recorded. Any new treatment-induced cranial nerve neuropathy was scored as a complication. RESULTS Median follow-up was 62 months (range, 6-136 months), 5 patients progressed, resulting in an overall 5-year local tumor control of 95%. The overall 5-year facial nerve preservation probability was 88% and facial nerve neuropathy was statistically significantly higher after SRS, after prior surgery, for larger tumors, and in Koos Grade ≥3. The overall 5-year trigeminal nerve preservation probability was 96%, not significantly influenced by any of the risk factors. The overall 4-year probability of preservation of useful hearing (Gardner-Robertson score 1 or 2) was 68%, not significantly different between SRS or SRT (59% vs. 82%, p = 0.089, log rank). CONCLUSION Linac-based RT results in good local control and acceptable clinical outcome in small to medium-sized vestibular schwannomas (VSs). Radiosurgery for large VSs (Koos Grade ≥3) remains a challenge because of increased facial nerve neuropathy.

NMDA-mediated release of glutamate and GABA in the subthalamic nucleus is mediated by dopamine: an in vivo microdialysis study in rats

The present study investigated the effects of N‐methyl‐D‐aspartic acid·H2O (NMDA) on the dopamine, glutamate and GABA release in the subthalamic nucleus (STN) by using in vivo microdialysis in rats. NMDA (100 μmol/L) perfused through the microdialysis probe evoked an increase in extracellular dopamine in the STN of the intact rat of about 170%. This coincided with significant increases in both extracellular glutamate (350%) and GABA (250%). The effect of NMDA perfusion on neurotransmitter release at the level of the STN was completely abolished by co‐perfusion of the selective NMDA‐receptor antagonist MK‐801 (10 μmol/L), whereas subthalamic perfusion of MK‐801 alone had no effect on extracellular neurotransmitter concentrations. Furthermore, NMDA induced increases in glutamate were abolished by both SCH23390 (8 μmol/L), a selective D1 antagonist, and remoxipride (4 μmol/L), a selective D2 antagonist. The NMDA induced increase in GABA was abolished by remoxipride but not by SCH23390. Perfusion of the STN with SCH23390 or remoxipride alone had no effect on extracellular neurotransmitter concentrations. The observed effects in intact animals depend on the nigral dopaminergic innervation, as dopamine denervation, by means of 6‐hydroxydopamine lesioning of the substantia nigra, clearly abolished the effects of NMDA on neurotransmitter release at the level of the STN. Our work points to a complex interaction between dopamine, glutamate and GABA with a crucial role for dopamine at the level of the STN.

NMDA receptor antagonism potentiates the L-DOPA-induced extracellular dopamine release in the subthalamic nucleus of hemi-parkinson rats.

Long term treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) is associated with several motor complications. Clinical improvement of this treatment is therefore needed. Lesions or high frequency stimulation of the hyperactive subthalamic nucleus (STN) in Parkinsons disease (PD), alleviate the motor symptoms and reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA dose. N-methyl-D-aspartate (NMDA) receptor antagonists might have similar actions. However it remains elusive how the neurochemistry changes in the STN after a separate or combined administration of L-DOPA and a NMDA receptor antagonist. By means of in vivo microdialysis, the effect of L-DOPA and/or MK 801, on the extracellular dopamine (DA) and glutamate (GLU) levels was investigated for the first time in the STN of sham and 6-hydroxydopamine-lesioned rats. The L-DOPA-induced DA increase in the STN was significantly higher in DA-depleted rats compared to shams. MK 801 did not influence the L-DOPA-induced DA release in shams. However, MK 801 enhanced the L-DOPA-induced DA release in hemi-parkinson rats. Interestingly, the extracellular STN GLU levels remained unchanged after nigral degeneration. Furthermore, administration of MK 801 alone or combined with L-DOPA did not alter the STN GLU levels in both sham and DA-depleted rats. The present study does not support the hypothesis that DA-ergic degeneration influences the STN GLU levels neither that MK 801 alters the GLU levels in lesioned and non-lesioned rats. However, NMDA receptor antagonists could be used as a beneficial adjuvant treatment for PD by enhancing the therapeutic efficacy of l-DOPA at least in part in the STN.

Development of dural plasmacytoma after evacuation of chronic subdural hematoma: Case report

A plasmacytoma is a monoclonal proliferation of mmunoglobulin-secreting plasma cells. Three forms of this ntity have been described, namely systemic multiple myeloma, olitary plasmacytoma of bone (SPB) and solitary extramedullary lasmacytoma (SEP). Whereas SPB is probably a variant of muliple myeloma, several authors suggest that SEP is a completely ifferent clinical entity. Differential diagnosis between multiple yeloma and solitary plasmacytoma is important as prognosis nd treatment differ greatly [1,9].

Dopaminergic Control of the Neurotransmitter Release in the Subthalamic Nucleus: Implications for Parkinson’s Disease Treatment Strategies

A critical role of the subthalamic nucleus (STN) in the control of movement has been proposed based on the observations that its lesion or high-frequency stimulation, aimed at altering its activity, is effective in alleviating clinical features of Parkinson’s disease (Bergman et al,. 1990; Bennazouz et al., 1993; Pollak et al., 1993, Benazzouz et al., 2000). Indeed, overactivity of the subthalamic neurons due to the loss of midbrain dopaminergic neurons is believed to be a key feature in Parkinson’s disease. Several studies indicate that the activity of STN neurons can be influenced directly by dopamine and its receptor agonists/antagonists. Indeed, the STN receives a direct dopaminergic input arising in the substantia nigra pars compacta (SNc) and both dopamine D1and D2-like receptors are present in the STN (Canteras et al., 1990; Hassani et al., 1997; Flores et al., 1999). Understanding the position of the STN within the basal ganglia and the possible direct effects of dopamine and its ligands at the level of this nucleus in normal and parkinsonian states may be important in the development of new therapies for Parkinson’s disease. The purpose of this chapter is to give an overview of the current position of the STN in the basal ganglia motorloop and to clarify the role of dopamine at the level of the STN in both normal conditions and in parkinsonian experimental animal models.