Surgical management for dystonia: Efficacy of deep brain stimulation in the long term

Introduction: Dystonia is a movement disorder substantially affecting the quality of life. Botulinum Neurotoxin (BoNT) is used intramuscularly as a treatment for dystonia; however, not all dystonia patients respond to this treatment. Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and essential tremor, but it can help in dystonia as well. Objectives: We studied a total of 67 dystonia patients who were treated with DBS over a period of 7 years to find out the long-term efficacy of DBS in those patients. First, we calculated patient improvement in post-surgery follow-up programs using the Global Dystonia Severity scale (GDS) and Burke–Fahn–Marsden dystonia rating scale (BFMDRS). Secondly, we analyzed the scales scores to see if there was any statistical significance. Methods: In our study we analyzed patients with ages from 38 to 78 years with dystonia who underwent DBS surgery between January 2014 and December 2020 in four different centers (India, Kuwait, Egypt, and Turkey). The motor response to DBS surgery was retrospectively measured for each patient during every follow-up visit using the GDS and the BFMDRS scales. Results: Five to 7 years post-DBS, the mean reduction in the GDS score was 30 ± 1.0 and for the BFMDRS score 26 ± 1.0. The longitudinal change in scores at 12 and 24 months post-op was also significant with mean reductions in GDS and BFMDRS scores of 68 ± 1.0 and 56 ± 1.0, respectively. The p-values were <0.05 for our post-DBS dystonia patients. Conclusions: This study illustrates DBS is an established, effective treatment option for patients with different dystonias, such as generalized, cervical, and various brain pathology-induced dystonias. Although symptoms are not completely eliminated, continuous improvements are noticed throughout the post-stimulation time frame

Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury

This study examined the effect of transfer of overlapping regions of chromosome 5 that includes (4A+) or excludes (4A−) the cytochrome P-450 4A (CYP4A) genes from the Lewis rat on the renal production of 20-hydroxyeicosatetraenoic acid (20-HETE) and the development of hypertension-induced renal disease in congenic strains of Dahl salt-sensitive (Dahl S) rats. The production of 20-HETE was higher in the outer medulla of 4A+ than in Dahl S or 4A− rats. Mean arterial pressure (MAP) rose to 190 ± 7 and 185 ± 3 mmHg in Dahl S and 4A− rats fed a high-salt (HS) diet for 21 days but only to 150 ± 5 mmHg in the 4A+ strain. Protein excretion increased to 423 ± 40 and 481 ± 37 mg/day in Dahl S and 4A− rats vs. 125 ± 15 mg/day in the 4A+ strain. Baseline glomerular capillary pressure (Pgc) was lower in 4A+ rats (38 ± 1 mmHg) than in Dahl S rats (42 ± 1 mmHg). Pgc increased to 50 ± 1 mmHg in Dahl S rats fed a HS diet, whereas it remained unaltered in 4A+ rats (39 ± 1 mmHg). Baseline glomerular permeability to albumin (Palb) was lower in 4A+ rats (0.19 ± 0.05) than in Dahl S or 4A− rats (0.39 ± 0.02). Palb rose to ∼0.61 ± 0.03 in 4A− and Dahl S rats fed a HS diet for 7 days, but it remained unaltered in the 4A+ rats. The expression of transforming growth factor-β2 was higher in glomeruli of Dahl S rats than in 4A+ rats fed either a low-salt (LS) or HS diet. Chronic administration of a 20-HETE synthesis inhibitor (HET0016; 10 mg·kg−1·day−1 sc) reversed the fall in MAP and renoprotection seen in 4A+ rats. These results indicate that the introgression of the CYP4A genes from Lewis rats into the Dahl S rats increases the renal formation of 20-HETE and attenuates the development of hypertension and renal disease

Deep Brain Stimulation of the Pedunculopontine Nucleus Area in Parkinson Disease MRI-Based Anatomoclinical Correlations and Optimal Target

International audienceBACKGROUND Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF