Objectives: Surgical treatment of complex cervical dystonia and of cervical dyskinesias associated with cervical myelopathy is challenging. In this prospective study, the long term effect of chronic pallidal stimulation in cervical dystonia and on combining the technique with spinal surgery in patients with severe cervical dyskinesias and secondary cervical myelopathy is described. Methods: Eight patients with a history of chronic dystonia who did not achieve adequate benefit from medical treatment or botulinum toxin injection participated in the study. Five patients had complex cervical dystonia with tonic postures and phasic movements. Three patients had rapidly progressive cervical myelopathy secondary to severe cervical dyskinesias and dystonia in the context of a generalised movement disorder. Quadripolar electrodes were implanted in the posteroventral lateral globus pallidus internus with stereotactic CT and microelectrode guidance. In the three patients with secondary cervical myelopathy, spinal surgery was performed within a few weeks and included multilevel laminectomies and a four level cervical corporectomy with spinal stabilisation. Results: Improvement of the movement disorder was noted early after pallidal surgery, but the full benefit could be appreciated only with a delay of several months during chronic stimulation. Three months after surgery, patients with cervical dystonia had improved by 38% in the severity score, by 54% in the disability score, and by 38% in the pain score of a modified version of the Toronto western spasmodic torticollis rating scale. At a mean follow up of 20 months, the severity score had improved by 63%, the disability score by 69%, and the pain score by 50% compared with preoperatively. There was also sustained amelioration of cervical dyskinesias in the three patients who underwent spinal surgery. Lead fractures occurred in two patients. The mean amplitude needed for chronic deep brain stimulation was 3.8 V at a mean pulse width of 210 µs, which is higher than that used for pallidal stimulation in Parkinson's disease. Conclusions: Chronic pallidal stimualtion is effective for complex cervical dystonia and it is a useful adjunct in patients with cervical dyskinesias and secondary cervical myelopathy who undergo spinal surgery.

Objective: To investigate the efficacy of chronic pallidal deep brain stimulation (DBS) on off period dystonia, cramps, and sensory symptoms in advanced Parkinson's disease (PD). Methods: 16 patients (6 women, 10 men; mean age at surgery 65 years) suffering from advanced PD were followed up prospectively for one year after implantation of a monopolar electrode in the posteroventral lateral globus pallidus internus. Unilateral DBS was performed in 9 patients. 10 patients had bilateral procedures (contemporaneous bilateral surgery in 7 and staged bilateral surgery in 3 instances). The decision whether to perform unilateral or bilateral surgery depended on the clinical presentation of the patient. Patients were formally assessed preoperatively, at 3-5 days, 3 months, and 12 months after surgery. Results: In patients who underwent unilateral surgery, pain was present in 7 (78%), off dystonia in 5 (56%), cramps in 6 (67%), and dysaesthesia in 4 (44%). In patients who underwent bilateral surgery, pain was present in 7 (70%), off dystonia in 6 (60%), cramps in 7 (70%), and dysaesthesia in 4 (40%). With unilateral DBS, contralateral off period dystonia was improved by 100% at 1 year postoperatively, pain by 74%, cramps by 88%, and dysaesthesia by 100%. There was less pronounced amelioration of ipsilateral off period dystonia and sensory symptoms. With bilateral DBS, total scores for dystonia were improved by 86%, for pain by 90%, for cramps by 90%, and for dysaesthesia by 88%. The benefit appeared early at the first evaluation 3-5 days after surgery and was stable throughout the follow up period. Conclusions: Pallidal DBS yields major improvement of off period dystonia, cramps, and sensory symptoms in patients with advanced PD.

Utrophin, an autosomal homologue of dystrophin, has been suggested as a possible therapeutic replacement of dystrophin in Duchenne or Becker muscular dystrophies (DMD/BMD). We have undertaken this study to examine the expression of utrophin in the skeletal muscle of dystrophin-deficient cats, a spontaneous animal model for dystrophinopathy. Dystrophin was normal in size, but very low in quantity by immunohistochemistry and Western blot. Utrophin was heterogeneously overexpressed at extrajunctional sarcolemma of regenerating muscle fibers, as defined by overexpression of the myogenic markers: vimentin, desmin, and developmental isoform of myosin heavy chain (MHCd). Muscle regeneration occurred in 6 stages as assessed by fiber size, and immunolabeling of desmin, vimentin, and MHCd. Differential developmental patterns of utrophin, alpha-sarcoglycan, and beta-dystroglycan expression were seen with an increase followed by a decrease and with changes in their respective location. These results suggest that utrophin is a regeneration-associated protein. It can functionally replace dystrophin in anchoring dystrophin-associated proteins (DAPs). However, the expression of utrophin and its anchored DAPs is restricted to the period of muscle regeneration and tends to decrease in late stages. This study therefore suggests a novel role of utrophin during skeletal muscle regeneration.

The changing roles of the hypothalamus and pituitary in regulating thyroid hormone levels in the rat during ontogeny has not been fully elucidated. It has been reported that endogenous TRH begins to stimulate TSH secretion at 5–8 days after birth but that the pituitary responds to hypothyroidism during late gestation. To determine the onset and extent of TRH response to low thyroid hormone levels during ontogeny, normal and hypothyroid rats treated with methimazole for 7 days were sacrificed at 16 days gestation (E16), 20 days gestation (E20), 7, 21 and 56 days after birth (n = 5/study group). Plasma hormones were assayed from pregnant mothers, pups (pooled) and adults. Levels of TRH mRNA were measured in the paraventricular nuclei (PVN) by in situ hybridization histochemistry. A labeled 48-base cDNA oligonucleotide for TRH was hybridized with brain slices (n = 6/animal) in the region of the medial parvocellular division of the PVN of the hypothalamus and the signal was quantitated by digitized computer analysis. Plasma-free T4 levels decreased and plasma TSH levels increased in the animals treated with methimazole as compared to the euthyroid controls. TRH mRNA was detected in the PVN at E16 after brain slices were dipped in emulsion and granules observed by dark-field microscopy. In the euthyroid animals, TRH mRNA increased from E20 (150 ± 9 OD units) to 7 days (222 ± 5 OD units) and remained unchanged at 21 days (252 ± 27 OD units) and 56 days (244 ± 6 OD units). The hypothyroid rats as compared to age-matched controls, had TRH mRNA levels that were unchanged at E16 and E20 and increased to 121% at 7 days (269 ± 9 0D units; p < 0.001), 176% at 21 days (461 ± 26 OD units; p < 0.001), and 225% at 56 days (545 ± 20 OD units; p < 0.001). In summary, TRH mRNA was present in the PVN at E16 and increased until 7 days after birth. TRH mRNA was not altered with hypothyroidism until after E20 and prior to or on the 7th day after birth when levels increased in response to low thyroid hormone levels. Thus, the ontogeny of the regulation of thyroid hormone feedback on TRH mRNA levels and of TSH secretion by endogenous TRH may be temporally associated suggesting an important role of PVN maturation in the development of the thyroid axis.