Word-level intelligibility after caudal zona incerta stimulation for Parkinson's disease.

OBJECTIVES: To investigate the effect of caudal zona incerta-deep brain stimulation (cZi-DBS) on word-level speech intelligibility in patients with Parkinson's disease, under both an optimal listening condition and a simulated more naturalistic listening condition. MATERIALS AND METHODS: Spoken single words were extracted from read samples collected from 10 bilaterally implanted patients with PD pre- and post-cZi-DBS. Intelligibility was assessed through a transcription task performed by 32 naive listeners under two listening conditions: (i) with low-amplitude conversational speech added as background and (ii) with no added background noise. The listeners' responses were scored in terms of agreement with the intended words. RESULTS: Post-operatively, the total intelligibility score was significantly lower when cZi stimulation was switched on compared with off, for both listening conditions (with and without added background noise). Intelligibility was also significantly lower on stimulation compared with preoperative recordings, but only when assessed in the listening condition without background noise. The listening condition with added background noise resulted in significantly lower intelligibility scores compared with the no added noise condition for all stimulation conditions. CONCLUSIONS: The results of this study indicate that cZi-DBS in patients with PD can be detrimental to word-level speech intelligibility.

Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization.

OBJECTIVE: The posterior subthalamic area (PSA) is an emerging but relatively unexplored target for DBS treatment of tremor. The aim of the study was to explore the area further by evaluating the spatial distribution and the characteristics of stimulation-induced side effects in this area. METHODS: Twenty-eight patients with essential tremor (ET) implanted with 33 DBS electrodes were evaluated concerning stimulation-induced side effects by testing each contact separately one year after surgery. The location of the side effects were plotted on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the area for visualization was created. RESULTS: Visualization of the contacts eliciting stimulation-induced side effects demonstrated that identical responses can be elicited from various points in the PSA and its vicinity. The majority of contacts inducing muscular affection and cerebellar symptoms, including dysarthria, could not be attributed to an effect on the internal capsule. Paresthesias, affecting various body parts were elicited throughout the area without a clear somatotopic pattern. CONCLUSION: Stimulation-induced side effects in the PSA and its vicinity were difficult to attribute to certain anatomical areas as the same response was induced from various locations. Therefore, this study could not provide a meaningful somatotopic map with regard to stimulation-induced side effects in the PSA.

Overall self-perceived health in Restless legs treated with intrathecal morphine.

OBJECTIVES: Restless legs syndrome (RLS) has a high prevalence in the general population. Treatment with intrathecal morphine has been shown to be successful in a small number of patients. Our aim was to quantify the effect on RLS-related symptoms, health and quality of life in three patients treated with intrathecal morphine. MATERIALS AND METHODS: Three patients with medically refractory RLS received an implanted pump for delivery of intrathecal morphine. Severity of RLS and self-assessed health were rated using the International Restless Legs Syndrome Study Group (IRLSSG) rating scale and the Short Form health survey (SF-36). Assessments were made preoperatively and after 6 months of follow-up. RESULTS: Preoperatively two patients had very severe RLS, scoring 35 and 36 on the IRLSSG rating scale, and one patient had severe RLS (score, 26). All three patients were free of symptoms of RLS post-operatively and also at the 6-month follow-up. The daily doses of intrathecal morphine ranged from 73 to 199 µg. Results from the SF-36 health survey showed that all three patients had a better physical health compared to before surgery. CONCLUSION: Intrathecal morphine may be efficient in the treatment for medically refractory RLS. All three patients became completely free of symptoms, and there was also improvement in self-perceived overall health.

Deep brain stimulation - effects on swallowing function in Parkinson's disease.

OBJECTIVE: In patients with Parkinson's disease (PD), deep brain stimulation of the subthalamic nucleus (STN DBS) is well recognized in improving limb function, but the outcome on swallowing function has rarely been studied. The aim of this work was to evaluate the effect of STN DBS on pharyngeal swallowing function in patients with PD using self-estimation and fiberoptic endoscopic evaluation of swallowing. METHODS: Eleven patients (aged 41-72, median 61 years) were evaluated preoperatively and at 6 and 12 months after STN DBS surgery. All patients were evaluated with self-estimation on a visual analogue scale, and eight of them with a fiberoptic endoscopic examination with a predefined swallowing protocol including Rosenbek's Penetration-Aspiration Scale, Secretion Severity Scale, preswallow spillage, pharyngeal residue, and pharyngeal clearance. RESULTS: The self-assessments of swallowing function revealed a subjective improvement with STN DBS stimulation, whereas the data from the swallowing protocol did not show any significant effect of the STN DBS treatment itself. The prevalence of aspiration was not affected by the surgery. CONCLUSIONS: The results show that swallowing function was not negatively affected by STN DBS and the risk of aspiration did not increase. Self-estimation of swallowing function showed a subjective improvement due to stimulation.

Leukocyte telomere length and its relation to food and nutrient intake in an elderly population.

BACKGROUND/OBJECTIVES: Shorter leukocyte telomere length (LTL) is associated with several chronic diseases, but only a few studies have assessed the association between dietary factors and LTL. Our objective was to study the association between fats, fruits, vegetables and LTL in a cross-sectional study design. We hypothesized that intakes of fruits and vegetables would be positively associated with LTL and that intakes of fats, and especially saturated fatty acids (SFAs), would be negatively associated with LTL. SUBJECTS/METHODS: LTL was measured by quantitative real-time polymerase chain reaction in 1942 men and women aged 57-70 years from the Helsinki Birth Cohort Study. We assessed the whole diet by a validated semiquantitative 128-item food-frequency questionnaire. RESULTS: In general, there were only a few significant results. However, total fat and SFA intake (P=0.04 and 0.01, respectively) were inversely associated with LTL in men adjusting for age and energy intake. In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits (P=0.05). We found no association between LTL and body mass index, waist-hip ratio, smoking, physical activity or educational attainment. CONCLUSIONS: In this cross-sectional study of elderly men and women, there were only a few statistically significant effects of diet, but in general they support the hypothesis that fat and vegetable intakes were associated with LTL.

Swallowing function in Parkinson's patients following Zona Incerta deep brain stimulation.

OBJECTIVE: The purpose of the present study was to examine whether there was a negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on pharyngeal swallowing function in Parkinson's patients (PD). There are no former reports including swallowing and cZI DBS. METHODS: Eight patients (aged 49-71 years; median 62) were evaluated pre- and post-operatively, at 6 and 12 months after DBS surgery. Evaluation tools were fiberoptic endoscopic evaluation of swallowing examinations and patients' self-assessments of their swallowing function including a visual analog scale and quality-of-life-related questions. The swallowing protocol included Rosenbek's Penetration-Aspiration Scale, Secretion Severity Scale and parameters for preswallow spillage, pharyngeal residue, and pharyngeal clearance. RESULTS: There was no clear-cut effect of neurostimulation post-operatively at 6 and 12 months on any of the swallowing parameters except for the preswallow spillage that was slightly worsened in the stimulation on condition 12 months post-operatively. The answers to the self assessment questions did not vary significantly. CONCLUSIONS: The effect of the stimulation on the swallowing function varied among individuals, but the overall outcome was that cZI DBS did not seem to have a negative influence on swallowing function in the eight patients studied.

Predicting improvement after surgery for palmar hyperhidrosis.

OBJECTIVES: Endoscopic transthoracic sympathectomy (ETS) is a surgical procedure used to improve Quality of Life (QoL) in patients with treatment resistant palmar hyperhidrosis (PHH). The aim of this study was to test the hypothesis that low preoperative scores on The Everyday Life Questionnaire (EDLQ) would predict QoL improvement after surgery. MATERIALS AND METHODS: Pre- and post-operative QoL scores from a series of 30 consecutive patients who underwent ETS at our institution were analyzed. RESULTS: Preoperative QoL scores was a significant predictor of post-operative improvement across all dimensions covered by the questionnaire. CONCLUSION: Preoperative low QoL can be used as a guide in selecting patients with most improved QoL after ETS.

Deep brain stimulation in the treatment of depression.

OBJECTIVE: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy-refractory major depressive disorder (MDD). METHOD: A review of the literature on DBS in the treatment of MDD was conducted. RESULTS: The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission. CONCLUSION: DBS is a promising treatment for therapy-refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.

Complications and side effects of deep brain stimulation in the posterior subthalamic area.

BACKGROUND: The posterior subthalamic area (PSA), including the zona incerta and prelemniscal radiation (Raprl), has recently been presented in number of publications as a promising target for deep brain stimulation (DBS) in the treatment of various movement disorders. In order to evaluate the safety of the procedure, we analyzed our initial 40 patients for complications and side effects. METHODS: 40 patients treated with PSA DBS for Parkinson's disease, essential tremor and other forms of tremor were included. RESULTS: The most severe complication was 1 transient mild hemiparesis and 1 infection. Minor complications and side effects were relatively frequent, including mild transient dysphasia in 22.5% of the patients. CONCLUSIONS: Few serious complications were encountered, and we consider the PSA to be a safe target for DBS.

Childhood BMI trajectories and the risk of developing young adult-onset diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the effects of childhood BMI growth dynamics on the risk of developing young adult-onset type 1 and type 2 diabetes. METHODS: Finnish national healthcare registers were used to identify individuals with diabetes diagnosed between 1992 and 1996 at 15-39 years of age. Non-diabetic control participants were chosen from the National Population Registry. Anthropometric measurements were obtained from the original child welfare clinic records. Only the case-control pairs with sufficient growth data recorded were included in the analyses (218/1,388 for type 1 diabetes [16%] and 64/1,121 for type 2 diabetes [6%]). Two developmental stages in BMI growth (the points of infancy maximum BMI and the BMI rebound) were examined, and conditional logistic regression was applied to the variables of interest. RESULTS: The risk for type 1 diabetes increased 1.19-fold per 1 kg/m(2) rise in the infancy maximum BMI (p = 0.02). In addition, there was a 1.77-fold increase in the risk for type 2 diabetes per 1 kg/m(2) rise in the level of BMI at the BMI rebound (p = 0.04). Higher values of BMI at these points corresponded to a larger BMI gain from birth to that developmental stage. Age at the infancy maximum BMI or age at the BMI rebound did not affect the risk for either type of diabetes. CONCLUSIONS/INTERPRETATION: The BMI gain in infancy among individuals who subsequently developed young adult-onset type 1 diabetes was faster than that of those who remained healthy. The excess BMI gain in individuals who developed young adult-onset type 2 diabetes could already be seen during early childhood.

Deep brain stimulation of the posterior subthalamic area in the treatment of tremor.

BACKGROUND: Several studies have described lesional therapy in the posterior subthalamic area (PSA) in the treatment of various movement disorders. Recently, some publications have illustrated the effect of deep brain stimulation (DBS) in this area in patients with Parkinson's disease, essential tremor, MS-tremor, and other forms of tremor. Even though the clinical series is small, the reported benefits prompted us to explore DBS in this area in the treatment of tremor. METHOD: Five patients with tremor were operated using unilateral DBS of the PSA. Two patients had dystonic tremor, one primary writing tremor, one cerebellar tremor and the other neuropathic tremor. All patients were assessed before and 1 year after surgery using items 5 and 6 (tremor of the upper extremity), 11-14 (hand function), and when appropriate item 10 (handwriting) from the essential tremor rating scale. FINDINGS: The mean improvement on stimulation after 1 year was 87%. A pronounced and sustained microlesional effect was seen in several of the patients, and while the mean improvement off stimulation was 56% the reduction in the three patients with the most pronounced effect was 89%. The two patients with dystonic tremor did also become free of the dystonic symptoms and pain in the treated arm. No severe complication occurred. CONCLUSIONS: DBS of the PSA in this small group of patients had an excellent effect on the different forms of tremor, except for the neuropathic tremor where the effect was moderate. These preliminary results suggest PSA to be an effective target for the treatment of various forms of tremor. Further studies concerning indications, safety and efficacy of DBS in the posterior subthalamic area are required.

Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life.

OBJECTIVES: To report long-term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health-related quality of life (HRQoL) in patients with essential tremor (ET). MATERIALS AND METHODS: Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview. RESULTS: There was a decrease of DBS efficacy on tremor between 1 and 7 years post-operatively. The marked improvement in ADL at 1 year was no longer sustained at long-term, except for the ability to eat. Social life remained improved. CONCLUSION: Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co-morbidities may impact on the well-being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.

Sympathicotomy affects cutaneous blood flow, temperature, and sympathicus-mediated reflexes.

OBJECTIVE: To study the sympathetically mediated effects of transthoracic endoscopic sympathicotomy (TES) in the treatment of severe primary palmar hyperhidrosis. MATERIALS AND METHODS: The effects of TES, on sympathetic ganglia at the thoracic level of 2-3, finger blood flow, temperature, and on heat and cold provocation were investigated. Middle cerebral artery (MCA) blood flow velocities were studied by transcranial Doppler. RESULTS: The finger blood flow increased by about 700% after TES and finger temperature by 7.0 +/- 0.5 degrees C. Several autonomic reflexes were dramatically affected. A finger pulp-shrinking test showed a major decrease after surgery. MCA mean blood flow velocities were not affected by TES. CONCLUSIONS: Besides the high success rate of good clinical effect of TES on palmar hyperhidrosis, major effects on local blood flow and temperature are elicited by TES. Complex autonomic reflexes are also affected. The patient should be completely informed before surgery of the side effects elicited by TES.

Pallidal deep brain stimulation in the treatment of Meige syndrome.

BACKGROUND: Pallidal deep brain stimulation (DBS) of globus pallidus internus (Gpi) has emerged as an effective treatment for dystonia. The experience is however limited concerning focal dystonias and to date only a few cases of pallidal DBS in the treatment of Meige syndrome have been published. METHODS/RESULTS: We here present a patient with Meige syndrome in whom unilateral pallidal DBS failed to improve the axial symptoms, but bilateral stimulation resulted in a major improvement. The Burke-Fahn-Marsden score (BFM) improved by 71.5% and the patient's blepharospasm was abolished. CONCLUSIONS: The results suggest bilateral pallidal DBS may be an effective treatment for Meige syndrome.

The effect of birth order and parental age on the risk of type 1 and 2 diabetes among young adults.

AIMS/HYPOTHESIS: The aim of this study was to examine the effects of birth order and parental age on the risk of type 1 and type 2 diabetes among Finnish individuals aged 15-39 years. METHODS: Data on all cases of type 1 diabetes (n = 1,345) and type 2 diabetes (n = 1,072), diagnosed between 1992 and 1996, were collected from four sources: standardised national reports from diabetes nurses, the National Hospital Discharge Register, the Drug Prescription Register and the Drug Reimbursement Register. Information on matched controls and the family members of all study subjects were obtained from the National Population Registry. The odds ratios (ORs) for both types of diabetes were estimated using a conditional logistic regression model. RESULTS: There was a U-shaped relationship between maternal age and the risk of type 2 diabetes in the offspring: the risk was higher in children born to young and old mothers compared with children born to mothers aged around 30 years. The children born second (OR 0.76, 95% CI 0.62-0.94), third (OR 0.73, 95% CI 0.55-0.95), or fourth (OR 0.66, 95% CI 0.47-0.94) had a lower risk of type 2 diabetes than the first-born children. Maternal age, paternal age, and birth order did not have an effect on the risk of type 1 diabetes in the individuals aged 15-39 years at the time of diagnosis. CONCLUSIONS/INTERPRETATION: Maternal age and birth order are both associated with the risk of early-onset type 2 diabetes. However, part of these associations may be due to low birthweight. In this study neither parental age nor birth order showed a significant association with the risk of type 1 diabetes diagnosed after 15 years of age.

Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up.

Deep brain stimulation (DBS) of the nucleus ventralis intermedius thalami (Vim) in the treatment of essential tremor (ET) is well documented concerning the acute effects. Reports of the long-term effects are, however, few and the aim of the present study was to analyse the long-term efficacy of this treatment. Nineteen patients operated with unilateral Vim-DBS were evaluated with the Essential Tremor Rating Scale (ETRS) before surgery, and after a mean time of 1 and 7 years after surgery. The ETRS score for tremor of the contralateral hand was reduced from 6.8 at baseline to 1.2 and 2.7, respectively, on stimulation at follow-up. For hand function (item 11 - 14) the score was reduced from 12.7 to 4.1 and 8.2, respectively. Vim-DBS is an efficient treatment for ET, also after many years of treatment. There is, however, a decreasing effect over time, most noticeable concerning tremor of action.

Variability of the subthalamic nucleus: the case for direct MRI guided targeting.

Because of concerns about direct visualization of the subthalamic nucleus (STN) on magnetic resonance imaging (MRI), many functional neurosurgeons continue to rely on atlas-based coordinates to reach this target. T2-weighted MRI does allow direct visualisation of the STN. In order to compare the coordinates of the target point within the visualised STN with those obtained from standard brain atlases, the preoperative stereotactic T2-weighted MRI used to implant 55 deep brain stimulation electrodes in the visualised STN of 29 consecutive patients with Parkinson's disease treated in two European centres were studied. The coordinates of the directly visualised STN were significantly different from those of the atlas target. Variability of the position of the STN may render direct visualisation a more accurate means of targeting this nucleus.

Smoking and non-smoking tobacco as risk factors in subarachnoid haemorrhage.

OBJECTIVE: Swedish snuff is a particular form of non-smoking tobacco with high nicotine content. It is unknown whether this form of tobacco is a risk factor similar to smoking for suffering subarachnoid haemorrhage (SAH). In the present study we report our finding concerning smoking and snuff as risk factors for the disease. METHOD: We analysed 120 consecutive patients with SAH regarding consumption of tobacco, in order to evaluate if snuff also is associated with an increased risk of SAH. RESULTS: The relative risk of SAH was about 2.5 times higher for smokers compared with the background population. Consumption of snuff was not associated with an increased risk. CONCLUSIONS: It seems unlikely that nicotine is solely responsible for the rupture of cerebral aneurysms. The final cause of the increased risk for suffering SAH has to be sought in other factors associated with tobacco smoking.

Hardware-related complications of deep brain stimulation: a ten year experience.

OBJECTIVE: To analyse the occurrence of hardware-related complications in patients with deep brain stimulation (DBS), over a long period of time. METHOD: All patients operated on with DBS at our institution between 1993 and 2002 were followed with respect to adverse events related to the implanted hardware. RESULTS: One hundred and nineteen consecutive patients underwent 139 procedures with implantation of 161 electrodes. The minimum follow-up was 12 months. The follow-up time was 540 electrode-years. The rate of hardware-related complications per electrode-year was 4.3%. In total, 17 patients (15%) had 23 hardware-related complications. These included 8 electrode breakages, 4 electrode migrations, 2 stimulator migrations, 3 erosions, 2 erosions and infections, 2 infections and 2 cases of stimulator malfunction. The majority of these complications occurred during the first four years in our experience. CONCLUSIONS: DBS is a life-long therapy that requires a life-long follow-up. Increased experience and adaptation of surgical technique are the main determinants for avoidance of hardware-related complications.