Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission.

Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury and deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed to underlie tic behaviour, evidence is scarce and inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory Tourette syndrome, may reduce tics by affecting striatal dopamine release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments and behavioural measurements to mechanistically examine how thalamic DBS modulates synaptic and tonic dopamine activity in the dorsomedial striatum. Previous studies demonstrated focal disruption of GABAergic transmission in the dorsolateral striatum of rats led to repetitive motor tics recapitulating the major symptom of Tourette syndrome. We employed this model under light anaesthesia and found CMPf DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons while concomitantly reducing motor tic behaviour. The improvement in tic behaviour was found to be mediated by D2 receptor activation as blocking this receptor prevented the therapeutic response. Our results demonstrate that release of striatal dopamine mediates the therapeutic effects of CMPf DBS and points to striatal dopamine dysfunction as a driver for motor tics in the pathoneurophysiology of Tourette syndrome.

Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: a national multi-center study.

PURPOSE: To compare the incidence and severity of acute and chronic hematologic toxicity (HT) in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for curative treatment of cervical cancer and to ascertain the dosimetric parameters of two techniques associated with acute and chronic HT. MATERIALS AND METHODS: A total of 127 patients with cervical cancer receiving concomitant pelvic radiotherapy (RT) and cisplatin were evaluated. Pelvic bone marrow (BM) was contoured for each patient and divided into five sub-regions: lumbosacrum (LS), ilium (IL), lower pelvis (LP), pelvis (P), and whole pelvis (WP). The volume of each BM region receiving 10, 20, 30, and 40 Gy was calculated (V10, -V20, -V30, and -V40). The lowest level of hemoglobin, leukocyte, neutrophil, and platelet counts were obtained during chemoradiotherapy and six months after RT. The nadir values were graded according to Common Terminology Criteria for Adverse Events (version 3.0). RESULTS: Grade 2 or greater acute anemia, leukopenia, neutropenia, thrombocytopenia was observed in 2%, 41.5%, 12% ,and 0% in 3DCRT group and in 27%, 53%, 24.5%, and 4.5% in IMRT group, respectively. Grade 2 or greater chronic anemia, leukopenia, neutropenia, and thrombocytopenia was observed in 11%, 10%, 6%, and 0% in 3DCRT group and in 11%, 9%, 4.5%, and 0% in IMRT group, respectively. LS-V30, 40; IL-V10, 20, 30, 40; LP-V10, 20 ,40; P-V10, 20, 30, 40, and TP-V10, 20, 30, 40 were significantly reduced with IMRT planning compared to 3DCRT planning. Logistic regression analysis of potential predictors showed that none of the dosimetric parameters were significant for predicting acute and chronic HT. CONCLUSION: The present findings showed that IMRT planning reduced irradiated BM volumes compared to 3DCRT planning. However, no difference between the two techniques was observed in terms of acute and chronic HT. Further studies are needed to confirm these results.