Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

<p>Abstract</p> <p>Background</p> <p>Radiation induced optic neuropathy (RION) is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide.</p> <p>Case Presentation</p> <p>The case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg) the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed.</p> <p>Conclusions</p> <p>In this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy.</p

Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in human M1HAND. TBS is a patterned rTMS protocol with intermittent TBS (iTBS) usually inducing a lasting increase and continuous TBS (cTBS) a lasting decrease in corticospinal excitability. In three separate sessions, healthy val(66)met (n = 12) and val(66)val (n = 17) carriers received neuronavigated cTBS followed by cTBS (n = 27), cTBS followed by iTBS (n = 29), and iTBS followed by iTBS (n = 28). Participants and examiner were blinded to the genotype at the time of examination. As expected, the first TBS intervention induced a decrease (cTBS) and increase (iTBS) in corticospinal excitability, respectively, at the same time priming the after effects caused by the second TBS intervention in a homeostatic fashion. Critically, val(66)met carriers and val(66)val carriers showed very similar response patterns to cTBS and iTBS regardless of the order of TBS interventions. Since none of the observed TBS effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND

Effects of the three TBS-TBS protocols and BDNF polymorphism on corticospinal excitability over time: (A) MEP_bi amplitude independent of polymorphism, (B) MEP_bi amplitude divided by polymorphism, (C) MEP_mo amplitude independent of polymorphism, (D) MEP_mo amplitude divided by polymorphism.

<p>Asterisks indicate significant changes from baseline in the expected direction as revealed by one-sided one-sample t-tests (^#P<0.05, *P<0.01, **P<0.001, ***P<0.0001, ****P<0.00001, *****P<0.000001; please note that p-values indicated by one or more asterisks are also significant when applying two-sided t-tests).</p

Effect of preconditioning on the after-effects of cTBS: (A) MEP_bi amplitude independent of polymorphism, (B) MEP_bi amplitude divided by polymorphism, (C) MEP_mo amplitude independent of polymorphism, (D) MEP_mo amplitude divided by polymorphism.

<p>Asterisks indicate significant changes from baseline in the expected direction as revealed by one-sided one-sample t-tests (^#P<0.05, *P<0.01, **P<0.001; please note that p-values indicated by one or more asterisks are also significant when applying two-sided t-tests). Actual p-values are given for post-hoc two-sided paired t-tests comparing different conditions.</p

Time line of an experimental session.

<p>The experiment consisted of three of these sessions in each of which two different TBS protocols were subsequently applied: iTBS followed by iTBS (i-iTBS), cTBS followed by iTBS (c-iTBS), and cTBS followed by cTBS (c-cTBS).Motor evoked potentials (MEPs) were recorded at the contralateral FDI muscle both with biphasic pulses (MEP_bi) at baseline as well as 5 and 25 minutes after the end of each TBS intervention and with monophasic pulses (MEP_mo) at baseline, and 10 min after the end of each TBS intervention. Session were randomized in order across subjects and were conducted at least five days apart.</p