Small and large fiber neuropathy in adults with myotonic dystrophy type 1.

Introduction: Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder that affects multiple organs. In this study, we investigated symptoms of pain and presence of small and large fiber neuropathy in the juvenile and adult form of DM1. Method: Twenty genetically verified DM1 patients were included. Pain was assessed, and neurological examination and investigations of the peripheral nervous system by quantification of small nerve fibers in skin biopsy, quantitative sensory testing and nerve conduction studies were performed. Results from skin biopsies were compared to healthy controls. Result: Seventeen patients reported chronic pain. Large and/or small fiber abnormalities were present in 50% of the patients. The intraepidermal nerve fiber density was significantly lower in the whole group of patients compared to healthy controls. Conclusion: Small-fiber neuropathy might be an important cause of pain in DM1.

Deep Brain Stimulation for Arm Tremor: A Randomized Trial Comparing Two Targets.

OBJECTIVE: Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) effectively suppresses arm tremor. Uncontrolled studies suggest the posterior subthalamic area (PSA) may be superior. We compared the intra-individual efficacy of VIM- versus PSA-DBS on tremor suppression and arm function. METHODS: We performed a randomized, double-blind, crossover trial at Oslo University Hospital in patients (18-80 years) with isolated or combined action tremor affecting at least one arm. Four-contact DBS leads were implanted (bi- or unilaterally) with a trajectory to cover the VIM (upper two contacts) and PSA (lower two contacts). Patients were randomized (1:1 ratio) post-surgery to: Group 1, VIM-stimulation months 0-3 (period 1), then PSA-stimulation months 4-6 (period 2); Group 2, PSA-stimulation first, then VIM-stimulation. Primary endpoint was the difference in improvement from baseline to the end of the VIM- versus PSA-period in the sum of the dominant arm tremor scores of the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), items 5/6 + 10-14. RESULTS: Forty-five patients were randomized to Group 1 (n = 23) or 2 (n = 22). In the primary endpoint per-protocol analysis (mixed model, n = 40), mean difference in the sum FTMTRS score improvement for the dominant arm was -2.65 points (95% CI -4.33 to -0.97; p = 0.002). The difference in favour of PSA stimulation was highly significant in period 2, but not period 1. INTERPRETATION: Our randomized trial demonstrated that PSA stimulation provided superior tremor suppression compared with VIM stimulation. A period effect reducing tremor for up to three months in both groups was most likely attributed to a post-surgery stun effect. ANN NEUROL 2022;91:585-601.

Subthalamic Nucleus Stimulation in Parkinson's Disease: 5-Year Extension Study of a Randomized Trial.

BACKGROUND: In Parkinson's disease (PD) long-term motor outcomes of subthalamic nucleus deep brain stimulation (STN-DBS) are well documented, while comprehensive reports on non-motor outcomes are fewer and less consistent. OBJECTIVE: To report motor and non-motor symptoms after 5-years of STN-DBS. METHODS: We performed an open 5-year extension study of a randomized trial that compared intraoperative verification versus mapping of STN using microelectrode recordings. Changes from preoperative to 5-years of STN-DBS were evaluated for motor and non-motor symptoms (MDS-UPDRS I-IV), sleep disturbances (PDSS), autonomic symptoms (Scopa-Aut), quality of life (PDQ-39) and cognition through a neuropsychological test battery. We evaluated whether any differences between the two randomization groups were still present, and assessed preoperative predictors of physical dependence after 5 years of treatment using logistic regression. RESULTS: We found lasting improvement of off-medication motor symptoms (total MDS-UPDRS III, bradykinetic-rigid symptoms and tremor), on-medication tremor, motor fluctuations, and sleep disturbances, but reduced performance across all cognitive domains, except verbal memory. Reduction of verbal fluency and executive function was most pronounced the first year and may thus be more directly related to the surgery than worsening in other domains. The group mapped with multiple microelectrode recordings had more improvement of bradykinetic-rigid symptoms and of PDQ-39 bodily discomfort sub-score, but also more reduction in word fluency. Older age was the most important factor associated with physical dependence after 5 years. CONCLUSION: STN-DBS offers good long-term effects, including improved sleep, despite disease progression. STN-DBS surgery may negatively impact verbal fluency and executive function.

Direct visual targeting versus preset coordinates for ANT-DBS in epilepsy.

OBJECTIVES: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) may be used against refractory focal epilepsy, but only two randomized double-blinded trials have been performed. The Oslo study was discontinued prematurely since reduction in seizure frequency was less than expected. The aim of the present study was to review the targeting used in the Oslo study and to identify the actual positions of the contacts used for stimulation. MATERIAL AND METHODS: BrainLab MRI data were available from 12 Oslo study patients. Based on MRI the coordinates of the center of the ANT were identified. The coordinates were considered as the visually identified preferred target and were compared with the target originally used for ANT electrode implantation and with the actual electrode positions estimated from post-operative CT scans. RESULTS: We found considerable differences between the visually identified preferred target, the originally planned target, and the actual electrode position. The total distance between the active electrode position and the visually identified preferred target was on average 3.3 mm on the right and 2.9 mm on the left side. CONCLUSION: Indirect targeting based on preset coordinates may contribute to explain the modest effect of ANT-DBS on seizure frequency seen in the Oslo study. Observed differences between the center of the ANT and the actual electrode position may at least in part be explained by variations in position and size of the ANT. Direct identification of the target using better MRI imaging protocols is recommended for future ANT-DBS surgery.

Multiple Microelectrode Recordings in STN-DBS Surgery for Parkinson's Disease: A Randomized Study.

BACKGROUND: Subthalamic nucleus deep brain stimulation improves motor symptoms and fluctuations in advanced Parkinson's disease, but the degree of clinical improvement depends on accurate anatomical electrode placement. Methods used to localize the sensory-motor part of the nucleus vary substantially. Using microelectrode recordings, at least three inserted microelectrodes are needed to obtain a three-dimensional map. Therefore, multiple simultaneously inserted microelectrodes should provide better guidance than single sequential microelectrodes. We aimed to compare the use of multiple simultaneous versus single sequential microelectrode recordings on efficacy and safety of subthalamic nucleus stimulation. METHODS: Sixty patients were included in this double-blind, randomized study, 30 in each group. Primary outcome measures were the difference from baseline to 12 months in the MDS-UPDRS motor score (part III) in the off-medication state and quality of life using the Parkinson's Disease Questionnaire-39 (PDQ-39) scores. RESULTS: The mean reduction of the MDS-UPDRS III off score was 35 (SD 12) in the group investigated with multiple simultaneous microelectrodes compared to 26 (SD 10) in the single sequential microelectrode group (p = 0.004). The PDQ-39 Summary Index did not differ between the groups, but the domain scores activities of daily living and bodily discomfort improved significantly more in the multiple microelectrodes group. The frequency of serious adverse events did not differ significantly. CONCLUSIONS: After 12 months of subthalamic nucleus stimulation, the multiple microelectrodes group had a significantly greater improvement both in MDS-UPDRS III off score and in two PDQ-39 domains. Our results may support the use of multiple simultaneous microelectrode recordings. TRIAL REGISTRATION: http://ClinicalTrials.gov Identifier: NCT00855621 (first received March 3, 2009).

Neuroprotective effects of hypothermia.

BACKGROUND: The neuroprotective effects of hypothermia have been shown in case reports and animal studies. Therapeutic hypothermia is used to provide neuroprotection during certain types of surgery and after serious events that pose a threat to the brain. The aim of this review is to describe the efficacy of such treatment in adults. METHOD: All articles retrieved from five searches in PubMed were examined. Studies were included if they had a hypothermia protocol and a measurement of neuroprotection. The list of randomised studies was completed using studies identified from five international review articles. In all, 103 of 678 studies fulfilled the inclusion criteria, of which 48 were clinical trials. Ten of the clinical trials were randomised, using a normothermic control group. RESULTS: Several randomised clinical trials have suggested that avoidance of hyperthermia provides the same neuroprotection as therapeutic hypothermia after cardiac arrest and traumatic brain injury, but prognostic factors and inclusion criteria vary markedly between the patient populations, including time to target temperature. Two studies found that cognitive function after prolonged aortic surgery under deep hypothermia was equivalent to that after brief normothermic interventions. Animal studies show a neuroprotective effect of hypothermia, but this is dependent on the extent of anoxic damage as well as the rate of cooling. INTERPRETATION: It remains uncertain how best to implement therapeutic hypothermia to achieve neuroprotection after acute events that pose a threat to the brain. Hypothermia during aortic surgery seems to provide adequate neuroprotection for prolonged interventions.

Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation.

Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS.

Personality changes after deep brain stimulation in Parkinson's disease.

Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson's disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P = 0.006; P = 0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P = 0.027). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity.

Surgical site infections after deep brain stimulation surgery: frequency, characteristics and management in a 10-year period.

BACKGROUND/AIMS: Deep brain stimulation (DBS) implant infection is a feared complication, as it is difficult to manage and leads to increased patient morbidity. We wanted to assess the frequency and possible risk factors of DBS related infections at our centre. In the purpose of evaluating treatment options, we also analyzed treatment, and the clinical and microbiological characteristics of the infections. METHODS: Electronic medical records of all patients undergoing DBS surgery at our centre, from 2001 through 2010, were retrospectively reviewed. RESULTS: Of the 588 procedures performed 33 (5.6%) led to an infection. Some patients underwent several procedures, thus 32 out of totally 368 patients (8.7%), and 19 out of 285 patients (6.7%) who received primary lead implantation, developed an infection. Most infections (52%) developed within the first month and 79% within three months. In the majority of the infections (79%) hardware removal was performed. Staphylococcus aureus infections were the most frequent (36%), and more likely to have earlier onset, pus formation, a more aggressive development and lead to hardware removal. No risk factors were identified. CONCLUSIONS: Our results indicate that infections with more severe symptoms and growth of staphylococcus aureus should be treated with local hardware removal and antibiotic therapy. In other infections, an initial trial of antibiotic treatment could be considered. New knowledge about the microbiology of DBS related infections may lead to more effective antimicrobial treatment.

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.

Long-term efficacy and mortality in Parkinson's disease patients treated with subthalamic stimulation.

BACKGROUND: The objective of this study was to examine the clinical outcome and mortality of long-term deep brain stimulation of the subthalamic nucleus in advanced Parkinson's disease. METHODS: We included all 144 patients (mean age, 60.3 years; mean disease duration, 11.0 years) treated in our center from 2001 to 2007. RESULTS: Twelve months after surgery, the off-medication Unified Parkinson's Disease Rating Scale motor score was reduced by a mean of 53%, and the annual increase after surgery was 3.2 points. The daily dose of dopaminergic medication was reduced by a mean of 49% and increased only marginally during follow-up. Twelve of the 144 patients died in the study period, including 2 suicides (1.4%). Survival was 97% after 3 years and 90% after 5 years. CONCLUSIONS: The study confirms the stable efficacy of long-term subthalamic stimulation in selected patients with advanced Parkinson's disease. Throughout the study the patient characteristics at time of surgery changed, with less severe disease and shorter disease duration toward the end of the study period.