Effects of anterior thalamic nucleus DBS on interictal heart rate variability in patients with refractory epilepsy.

OBJECTIVE: Heart rate variability (HRV) changes were investigated by several studies after resective epilepsy surgery/vagus nerve stimulation. We examined anterior thalamic nucleus (ANT)-deep brain stimulation (DBS) effects on HRV parameters. METHODS: We retrospectively analyzed 30 drug-resistant epilepsy patients' medical record data and collected electrocardiographic epochs recorded during video- electroencephalography monitoring sessions while awake and during N1- or N2-stage sleep pre-DBS implantation surgery, post-surgery but pre-stimulation, and after stimulation began. RESULTS: The mean square root of the mean squared differences between successive RR intervals and RR interval standard deviation values differed significantly (p < 0.05) among time-points, showing increased HRV post-surgery. High (0.15-0.4 Hz) and very low frequency (<0.04 Hz) increased, while low frequency (0.04-0.15 Hz) and the LF/HF ratio while awake decreased, suggesting improved autonomic regulation post-surgery. Change of effect size was larger in patients where both activated contacts were located in the ANT than in those where only one or none of the contacts hit the ANT. CONCLUSIONS: In patients with drug-resistant epilepsy, ANT-DBS might positively influence autonomic regulation, as reflected by increased HRV. SIGNIFICANCE: To gain a more comprehensive outcome estimation after DBS implantation, we suggest including HRV measures with seizure count in the post-surgery follow-up protocol.

Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation.

BACKGROUND: Several pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. OBJECTIVE: We conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. MATERIALS AND METHODS: A total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society-sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson's Disease Questionnaire (PDQ-39) were assessed. RESULTS: According to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. CONCLUSIONS: Directional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

Examination of pituitary adenylate cyclase-activating polypeptide in Parkinson's disease focusing on correlations with motor symptoms.

The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson's disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson's disease sleep scale (PDSS-2), and Beck depression inventory (BDI). Our results showed significantly decreased PACAP levels in PD patients without deep brain stimulation (DBS) therapy and in akinetic-rigid subtype; additionally we also observed a further decrease in the HY stage 3 and 4. Elevated PACAP levels were found in patients with DBS. There were no significant correlations between PACAP level with MDS-UPDRS, type of pharmacological treatment, PDSS-2 sleepiness, or depression (BDI) scales, but we found increased PACAP level in patients with more severe sleepiness problems based on the ESS scale. Based on these results, we suggest that following the alterations of PACAP with other frequently used clinical biomarkers in PD patients might improve strategic planning of further therapeutic interventions and help to provide a clearer prognosis regarding the future perspective of the disease.

Pregnancy and deep brain stimulation therapy for epilepsy.

Neuromodulation therapy -vagus nerve stimulation (VNS) and deep brain stimulation (DBS)- is one of the therapeutic options for drug-resistant epilepsy. With the increasing number of DBS implantations in women with epilepsy, it has become a burning issue whether DBS is safe in pregnancy. We report here two women with epilepsy who gave birth to healthy children with DBS therapy. We describe two cases, a 30-year-old woman and a 37-year-old woman. Both were implanted with DBS due to drug-resistant epilepsy. Both of our patients showed a significant improvement after DBS implantation and thereafter gave birth to a healthy child with DBS treatment. The severity and frequency of epileptic seizures did not change during pregnancy and after childbirth. Although a Caesarean section was performed in one case, pregnancies and births were essentially problem-free. At present, the two- and four-year-old children are healthy. Considering these cases, previously described VNS cases, and DBS cases with non-epileptic indications; we suggest that pregnancy and childbirth are safe in epilepsy patients with DBS, moreover, DBS treatment has probably no effect on foetal abnormalities or breastfeeding.

[Objective measurement of manual dexterity of Parkinson patients operated with DBS]. / DBS-mûtéttel kezelt Parkinson-kóros betegek kézügyesség-javulásának objektív mérése.

The evaluation of hand dexterity is an important marker for the success of DBS (deep brain stimulation) operation in patients with Parkinson's disease. In this study we applied a simple, semiquantitative optical dental plaque staining technique for the evaluation of the hand dexterity. Ten patient with Parkinson's disease were involved in the study. After dental students aided tooth brushing, bacterial dental deposits (plaque) were stained then photographed, and quantified under standard conditions before and after DBS surgery. Our results showed a significant decrease in dental plaque deposits after DBS operation. This simple technique seems to be a routinely applicable marker for the evaluation of the hand dexterity. Our future plans is repeating the previous experiement on a higher number of cases.

[Comparison of subthalamic nucleus planning coordinates in 1Tesla and 3Tesla MRI for deep brain stimulation targeting]. / A subthalamicus mag célkoordinátáinak összehasonlítása 1 és 3 Tesla MR-vizsgálattal mély agyi stimulációs mutétek tervezése során.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. METHODS: In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. RESULTS: The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). CONCLUSION: Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.

How Efficient Is Subthalamic Deep Brain Stimulation in Reducing Dyskinesia in Parkinson's Disease?

BACKGROUND: Dyskinesia is among the most troublesome symptoms of advanced Parkinson's disease (PD). The recently developed Unified Dyskinesia Rating Scale (UDysRS) can simultaneously measure several subjective and objective aspects of dyskinesia, irrespective of the other motor symptoms of PD. Despite the advantages of deep brain stimulation (DBS), previous studies on DBS have not used the UDysRS yet. METHODS: In this prospective study, 71 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. The severity of PD-related symptoms was assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS). The presence and severity of dyskinesia were specifically measured by the UDysRS and patient diaries. RESULTS: At baseline, all 71 patients had dyskinesia, but 1 year after DBS implantation, 25 patients were dyskinesia-free, and an additional 19 had only mild dyskinesia. The total score on the UDysRS decreased from 38.0 ± 17.8 to 10.8 ± 13.0 (p < 0.001). Besides this, all parts of the UDysRS showed significant improvement after STN DBS treatment, and the magnitude of these changes had a large effect size. The total score of MDS-UPDRS improved from 76.5 ± 24.3 to 60.4 ± 21.4 points (p < 0.001). CONCLUSIONS: Based on our results, UDysRS can reliably detect improvements in dyskinesia after DBS implantation.

Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report.

We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved.

Deep Brain Stimulation Can Preserve Working Status in Parkinson's Disease.

Objectives. Our investigation aimed at evaluating if bilateral subthalamic deep brain stimulation (DBS) could preserve working capability in Parkinson's disease (PD). Materials. We reviewed the data of 40 young (<60 year-old) PD patients who underwent DBS implantation and had at least 2 years of follow-up. Patients were categorized based on their working capability at time of surgery: "active job" group (n = 20) and "no job" group (n = 20). Baseline characteristics were comparable. Quality of life (EQ-5D) and presence of active job were evaluated preoperatively and 2 years postoperatively. Results. Although similar (approximately 50%) improvement was achieved in the severity of motor and major nonmotor symptoms in both groups, the postoperative quality of life was significantly better in the "active job" group (0.687 versus 0.587, medians, p < 0.05). Majority (80%) of "active job" group members were able to preserve their job 2 years after the operation. However, only a minimal portion (5%) of the "no job" group members was able to return to the world of active employees (p < 0.01). Conclusions. Although our study has several limitations, our results suggest that in patients with active job the appropriately "early" usage of DBS might help preserve working capability and gain higher improvement in quality of life.

Bilateral Subthalamic Stimulation can Improve Sleep Quality in Parkinson's Disease.

BACKGROUND: Sleep problems are among the most common non-motor symptoms of Parkinson's disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the original PDSS by adding more items on different aspects of sleep problems, making it a more robust tool to evaluate the severity of sleep disturbances. However, previous studies on deep brain stimulation (DBS) have not used the PDSS-2. OBJECTIVE: To determine if the PDSS-2 could detect improvement reliably in sleep problems after bilateral subthalamic nucleus DBS for PD. METHODS: In this prospective study, 25 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were specifically measured by PDSS-2. RESULTS: Total score of MDS-UPDRS improved from 81 (median, interquartile-range: 63-103) to 55 points (median, IQR: 46-75, p <  0.001). Health-related quality of life, measured by PDQ-39, also improved from 29 (IQR: 18-40) to 15 (IQR: 9-28) points (p = 0.002). Most domains of NMSS also improved. At baseline 13 patients reported sleep problems, but 1 year after DBS implantation only 3 did (p = 0.012). Although only 6 out of 15 items showed a significant decrease after DBS implantation, the total score of PDSS-2 decreased from 24 (IQR: 17-32) to 10 (IQR: 7-18) points (P <  0.001). CONCLUSIONS: Based on our results, PDSS-2 can detect improvements in sleep quality reliably after DBS implantation.

[EARLIER AND MORE EFFICIENTLY: THE ROLE OF DEEP BRAIN STIMULATION IN PARKINSON'S DISEASE: PRESERVING THE WORKING CAPABILITY]. / KORÁBBAN ÉS HATÉKONYABBAN: A MÉLY AGYI STIMULÁCIÓ SZEREPE A MUNKAKÉPESSÉG MEGORZÉSÉBEN.

BACKGROUND: The recently published "EarlyStim" study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. METHODS: We reviewed the data of 39 young (< 60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job ("Job+" group, n = 15) and retired patients (without active job, "Job-" group, n = 24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. RESULTS: As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p < 0.01, McNemar test). CONCLUSION: Although our retrospective study has several limitations, our results fit well with the conclusions of "EarlyStim" study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.

Effects of spinal cord stimulation on heart rate variability in patients with chronic pain.

BACKGROUND: Spinal cord stimulation has become an established clinical option for treatment of refractory chronic pain and angina pectoris, but its precise mechanism of action is unclear. We investigated the effect of spinal cord stimulation (SCS) on heart rate variability (HRV) and evaluating its influence on the sympathetic/parasympathetic balance in chronic pain. MATERIALS AND PURPOSE: Seven patients (three men, four women) with SCS due to chronic pain were included. The SCS was programmed in three different ways: (i) to stimulate at an amplitude known to generate paresthesias (ON-state), (ii) at a subliminal level (SUB state), or (iii) switched off (OFF-state). HRV analysis was based on 5-min segments of the consecutive normal RR intervals and was performed with custom software (Kubios HRV Analysis). RESULTS: The mean heart rate was higher in ON state compared to SUB state (p = 0.018) and the high-frequency component of the HRV was lower in ON compared to OFF period (p = 0.043). Other HRV parameters values did not significantly differ during the three tested periods. CONCLUSION: Spinal cord stimulation in chronic pain seems to be accompanied by reduced parasympathetic tone, unlike SCS in angina pectoris where previous studies found a reduced cardiac sympathetic tone. Our study might lead to understand the mechanism of action of SCS We investigated a relatively small number of patients, which is the main limitation of our study. Thus, further studies with larger number of patients are required for validation of our results.

[Treatment of dystonia by deep brain stimulation: a summary of 40 cases]. / Dystonia kezelése mély agyi stimulációval: 40 eset tapasztalatainak osszefoglalása.

BACKGROUND: Bilateral pallidal deep brain stimulation (DBS) is an established treatment option for primary generalized and segmental dystonia. In the present study we evaluated the results of our dystonia patients treated by DBS. METHODS: The surgical results of forty consecutive dystonia patients underwent DBS implantation were analyzed (age: 43.7 +/- 17.7 years; sex: 22 men; etiology: 24 primary and 16 secondary dystonia; topography: 24 generalized, 12 segmental and four hemidystonia; disease duration: 16.1 +/- 9.3 years). Severity of dystonia measured by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and health-related quality of life measured by EQ-5D scale were obtained preoperatively and compared to the scores obtained at postoperative six months and subsequent yearly follow-ups. The average follow-up lasted 2.5 years (median, 0.5-8 years). In all cases the BFMDRS scores were re-evaluated by a rater blinded to the treatment. Treatment responsiveness was defined as an at least 25% improvement on the BFMDRS scores. Non-parametric Mann-Whitney, McNemar and Kruskal-Wallis tests were applied to test statistical significance. RESULTS: Severity of dystonia improved from 31 to 10 points (median, 68% improvement, p < 0.01) in the primary dystonia group, whereas in secondary dystonia these changes were statistically insignificant (improvement from 40 to 31.5 points, 21.2%, p > 0.05). However, the health-related quality of life significantly improved in both groups (primary dystonia: 0.378 vs. 0.788 and secondary dystonia: 0.110 vs. 0.388, p < 0.01). Significantly more patients in the primary dystonia group responded to DBS treatment than those in the secondary dystonia group (83.3% vs. 37.5%, p < 0.01). CONCLUSION: Our results are in accordance with previously published international findings demonstrating that DBS is a highly effective and long-lasting treatment option for primary dystonia. DBS is considerably less efficient in secondary dystonia; however, it still has a high impact on the quality of life presumably due to its pain-relieving effect.

Status dystonicus: predictors of outcome and progression patterns of underlying disease.

BACKGROUND: Status dystonicus (SD) is a rare, life-threatening disorder characterized by acute worsening of generalized dystonia. METHODS: This study was conducted to characterize the pathogenesis, clinical course, and prognosis of SD. We reviewed the records of six centers and analyzed them together with all the cases previously reported in the literature. RESULTS: Eighty-nine episodes occurring in 68 patients were studied. The majority of patients were males (64.7%), were <15 years of age (58.8%), and had secondary dystonia as the underlying condition (37.8%). The episodes were mainly characterized by tonic muscle spasms (68.5%), with phasic forms more common in secondary forms and among females. Almost all cases needed a multistaged approach, with surgery being the most successful strategy. Neurological conditions preceding the episode worsened in 16.2% of cases (ending in death in 10.3%). CONCLUSIONS: The course and outcome of SD is highly variable; male gender and prevalent tonic phenotype predict a poor outcome.

[Role of deep brain stimulation in epilepsy]. / A mély agyi stimuláció szerepe az epilepszia kezelésében.

The deep brain stimulation (DBS) is an emerging treatment option in brain disorders in which randomized multicenter trials proved its efficacy leading to licensing different DBS methods in various brain diseases. More recently more and more brain structures have become candidates for being "target" in a possible DBS treatment of epilepsy. At present, only the DBS of the anterior nucleus of the thalamus (ANT) can be considered as a proved method for epilepsy treatment. Other potential targets for DBS treatment in epilepsy are the subthalamic nuclei, and the amygdala-hippocampus complex. There are some ongoing randomized studies to investigating their therapeutical role. The therapeutical outcome of ANT-DBS treatment in drug-resistant epilepsy seems to be better than the new antiepileptic drugs, but much worse than the results of a potential epilepsy surgery. At about 10% of patients may become seizure-free and 50% of patients may have a significant improvement. Nowadays ANT-DBS should be considered as an "ultima ratio" in those adult drug-resistant epilepsy patients with normal intelligence in which neither new antiepileptic drugs nor resective epilepsy surgery are a reasonable therapeutical options.

Reorganization of motor system in Parkinson's disease.

BACKGROUND/AIMS: We investigated adaptive reorganization in Parkinson's disease (PD) by fMRI using a passive movement task and compared the brain activation patterns of 10 patients with left- versus right-sided dominant symptoms. Five healthy controls were also investigated with the same settings. METHODS: We grouped patients according to the predominant side of symptoms; thus, a right-sided dominant and a left-sided dominant group was formed. The paradigm consisted of a 4-finger passive movement task, which altered with resting states. For each subject, this examination was performed twice: on the left and on the right hand separately. RESULTS: In healthy controls, motor-related areas contralateral to the moving fingers showed activation on fMRI. Concerning PD patients, motor-related areas of the ipsilateral hemisphere - including the primary motor cortex, supplementary motor area, and basal ganglia - seemed to be involved in the motor reorganization in PD. However, we could only demonstrate this reorganization in patients with right-sided dominant symptoms. CONCLUSIONS: We suggest that the human brain in PD tries to compensate for the failure of the basal ganglia motor loop by employing alternative (ipsilateral) motor pathways, indicating that a complex reorganization can also take place in disorders like PD which affect the whole motor-related network.

Comparison of the efficacy of unipolar and bipolar electrode configuration during subthalamic deep brain stimulation.

Deep brain stimulation of the subthalamic nuclei (STN) is a well established treatment in advanced Parkinson's disease (PD). Based on the clinical efficacy and elicited side-effects, both unipolar and bipolar stimulation modes may be applied. Bipolar stimulation usually produces a more focused and therefore thinner area of tissue activated during stimulation than unipolar stimulation does. The primary aim of our clinical study was to quantify the different clinical efficacy between these two stimulation modes. Twenty-one patients with PD previously underwent bilateral STN DBS implantation were involved in the study. Approximately three years after the implantation, we evaluated rigidity, tremor and bradykinesia according to the Unified Parkinson's disease Rating Scale in a practically off condition. Keeping the cathode of the chronic stimulation setting constant, the amplitude of stimulation was changed between 0 and 3.6 V by 0.2 V steps. Subsequently, the improvements in rigidity, tremor and bradykinesia were compared between unipolar and bipolar modes using 60 µs pulse-width and 130 Hz frequency. Within the examined amplitude range, unipolar stimulation usually had a significantly higher efficacy than bipolar stimulation; however, also with a higher rate of side-effects (19% vs. 0%). Depending on the evaluated parkinsonian symptoms, the efficacy of uni- and bipolar stimulation was different. To achieve the same level of improvement during bipolar stimulation, approximately 0.4-0.5 V higher amplitude was required than in unipolar mode. However in some cases, the efficacy of bipolar stimulation was unable the reach that of unipolar stimulation within the examined amplitude range.