Widespread white matter changes in post-H1N1 patients with narcolepsy type 1 and first-degree relatives.

Study Objectives: To assess white matter involvement in H1N1-vaccinated hypocretin deficient patients with narcolepsy type 1 (NT1) compared with first-degree relatives (a potential risk group) and healthy controls. Methods: We compared four diffusion tensor imaging-based microstructural indices (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) in 57 patients with NT1 (39 females, mean age 21.8 years, 51/57 H1N1-vaccinated, 57/57 HLA-DQB1*06:02-positive, 54/54 hypocretin-deficient), 54 first-degree relatives (29 females, mean age 19.1 years, 37/54 H1N1-vaccinated, 32/54 HLA-DQB1*06:02-positive), and 55 healthy controls (38 females, mean age 22.3 years). We tested for differences between these groups, for parametric effects (controls > first-degree relatives > patients) and associations in patients (cerebrospinal fluid [CSF] hypocretin-1 and disease duration) and first-degree relatives (HLA-DQB1*06:02 and H1N1-vaccination). We employed tract-based spatial statistics and used permutation testing and threshold-free cluster enhancement for inference. Results: Patients with NT1 had a widespread, bilateral pattern of significantly lower FA compared with first-degree relatives and healthy controls. Additionally, patients with NT1 also exhibited significantly higher RD and lower AD in several focal white matter clusters. The parametric model showed that first-degree relatives had intermediate values. Full sample of patients with NT1 showed no significant associations with disease duration or CSF hypocretin-1. Conclusions: Our study suggests widespread abnormal white matter involvement far beyond the already known focal hypothalamic pathology in NT1, possibly reflecting the combined effects of the loss of the widely projecting hypothalamic hypocretin neurons, and/or secondary effects of wake/sleep dysregulation. These findings demonstrate the importance of white matter pathology in NT1.

Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality.

BACKGROUND: Ventral intermediate thalamic nucleus (VIM) deep brain stimulation (DBS) is an effective treatment for tremor, but there is limited data on long-term efficacy and mortality after VIM-DBS. Here we report the analysis of patient satisfaction and mortality in all patients treated in our center 1996-2010 with VIM-DBS for essential tremor (ET). METHODS: Forty-six consecutive patients were included in this study. Medical records were reviewed, and a follow-up questionnaire was sent to all surviving patients. RESULTS: Seventy percent of all possible participants (26 patients) answered the questionnaire. Follow-up time for the responding patients was median 6.0 years (2-16). Median self-reported score on visual analogue scale of the initial postoperative effect on tremor was 8.5 (0.1-10), with a significant reduction to 7.4 (0-10) at follow-up (p = 0.001). Patients reported a median score of 10 (0-10) for overall patient satisfaction with VIM-DBS treatment. Eight patients (17%) died after median 8.9 years (0.6-15) after surgery, at median age 77.4 years (70-89). One patient (2%) committed suicide seven months after the operation. Calculated standard mortality ratio among ET patients was 1.3 (CI 0.6-2.6), similar to the general population. CONCLUSION: We found no significant increase in mortality in this cohort of VIM-DBS operated ET patients compared to the general population in Norway. The patients reported high long-term satisfaction and continuing effect of VIM-DBS on tremor even after many years. VIM-DBS therefore seems to be an effective symptomatic long-term treatment of ET. However, one patient committed suicide. Only one other suicide has previously been reported after VIM-DBS. It is therefore still unclear whether VIM-DBS increases suicide risk.

[Treatment of movement disorders with deep brain stimulation]. / Behandling av bevegelsesforstyrrelser med dyp hjernestimulering.

BACKGROUND: Deep brain stimulation is an established symptomatic treatment of movement disorders such as Parkinson's disease, tremor conditions and dystonia when medical treatment fails. We here present a review of indications and results for this treatment. We also present data om the activity related to patients with Parkinson's disease in a representative year and data on implantations performed Rikshospitalet University Hospital in the period 1999-2007. MATERIAL AND METHODS: The manuscript is based on non-systematic searches in PubMed, clinical experience, and internal statistics on implantations and clinical visits carried out at our centre. RESULTS AND INTERPRETATION: 243 procedures were performed in our clinic in the period; 187 for Parkinson's disease, 37 for tremor and 19 for dystonia. The vast majority of patients have been implanted with bilateral electrodes, and the targets were the subthalamic nucleus, the thalamus and the internal segment of globus pallidus. Studies have demonstrated that deep brain stimulation is an effective treatment of selected patients with Parkinson's disease, tremors and primary dystonia. Many of these patients have no other efficient treatment options. Patients should be referred for preoperative assessment when symptoms of their movement disorder can no longer be treated sufficiently with medical therapies and when their quality of life is impaired. A broad and careful evaluation of patients' symptoms and findings is important for correct patient selection for this treatment.