Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

Phonemic verbal fluency decline after subthalamic nucleus deep brain stimulation does not depend on number of microelectrode recordings or lead tip placement

BackgroundEvidence suggests that both motor improvement and decline in verbal fluency in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) may be attributed to a lead implantation effect.ObjectiveWe investigated whether the number of microelectrode recording (MER) passes influenced either motor UPDRS scores just prior to stimulation initiation at 4 weeks or decline in verbal fluency 6–24 months after surgery.MethodsWe retrospectively analyzed 50 PD patients who underwent bilateral STN DBS. Off medication UPDRS III motor scores were obtained before surgery and before stimulation was initiated. Neuropsychological testing was completed pre- and post-operatively in 28 patients at a mean of 377 days. Coordinates of lead tip and active stimulation site were calculated.ResultsThere was no improvement in off-medication UPDRS III motor scores at a mean 33.9 days following surgery, with mean change of 0.04 ± 10.48 (p = 0.98). There was no correlation between the number of MER passes and change in individual UPDRS motor score (r = −0.0001, p = 1.0). We observed significant decline in phonemic verbal fluency by 16% (p = 0.003) but it was not correlated with number of left hemisphere (r = −0.15, p = 0.46), or total number of passes (r = −0.02, p = 0.94) or coordinates of the lead tip or active stimulation site. There was a trend toward correlation with age (r = 0.38, p = 0.07).ConclusionsSignificant decline in phonemic verbal fluency did not correlate with surgical passes nor with location of the lead tip or active stimulation site. These data suggest that age may influence verbal fluency decline more than surgical technique.     

Correspondence of optimal stimulation and beta power varies regionally in STN DBS for Parkinson disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) for Parkinson disease (PD) normalizes neuronal hypersynchrony in the beta frequency range (13–30 Hz). The spatial correspondence of maximal beta power to the site of optimal stimulation along the DBS lead trajectory has been debated.MethodsWe determined the trajectory locations of the active contact, maximal beta power, and the dorsal border of the STN (DB-STN) in DBS patients. Beta power profiles were measured during intraoperative microelectrode recording (MER). Active contact locations were assigned during blinded, postoperative DBS programming. The DB-STN was identified both electrophysiologically during MER and anatomically on MRI. After grouping DBS trajectories into quadrants relative to the anatomic STN midpoint, we examined regional variations in the relative trajectory locations of the three entities.ResultsSTN DBS significantly improved motor performance for all 13 DBS patients, with active contacts at the DB-STN. Along trajectories passing posterior-medial to the STN midpoint, maximal beta power co-localized with active contacts at the DB-STN (difference Δ = 0.4 ± 1.6 mm, p = 0.57). By contrast, in posterior-lateral trajectories, maximal beta arose within the STN, ventral to active contacts (Δ = 1.9 ± 1.3 mm, p = 0.002). For trajectories anterior to the STN midpoint, maximal beta power co-localized with the DB-STN, while active contacts were ventral to peak beta power (p = 0.05).ConclusionOur findings indicate that co-localization of optimal stimulation and beta power varies by anatomical region in STN DBS for Parkinson disease.     

Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson’s disease

BackgroundNotwithstanding the large improvement in motor function in Parkinson’s disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role.ObjectiveWe studied whether apathy in DBS-treated PD patients could be a stimulation effect.MethodsIn 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy.ResultsAverage apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex.ConclusionsThe present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.     

Verbal Fluency in Essential Tremor Patients: The Effects of Deep Brain Stimulation

ObjectiveTo assess the effects of different frequencies of thalamic Deep-Brain-Stimulation (DBS) on cognitive performance of patients suffering from Essential Tremor (ET).MethodsIn 17 ET-patients with thalamic-DBS, Tremor-Rating-Scale (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word-Test and Digit-span-test were investigated in three randomized stimulation-settings: i) high-frequency stimulation (HFS), ii) low-frequency stimulation (LFS) and iii) OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one-way repeated measures analysis of variance for cognitive performance were calculated.ResultsTremor was reduced during HFS (Mean_TRS-HFS = 12.9 ± 9.6) compared to DBS-OFF (Mean_TRS-OFF = 44.4 ± 19.8, P < .001) and to LFS (Mean_TRS-10Hz = 50.0 ± 24.2; P < .001). While performance of Stroop-task and digit-span remained unaffected by stimulation-settings (P > .05), phonemic and semantic VF differed significantly between the three conditions (F_Pvf = 5.28, F_Svf = 3.41, both P < .05). Post-hoc comparisons revealed significant differences for both phonemic and semantic VF between LFS (Mean_Pvf-10Hz = 54.6 ± 9.2, Mean_Svf-10Hz = 56.4 ± 7.9) and HFS (Mean_Pvf-ON = 48.3 ± 11.4, Mean_Svf-ON = 51.1 ± 11.0, both P < .05), while DBS-OFF (Mean_Pvf-OFF = 51.2 ± 9.3, Mean_Svf-OFF = 53.6 ± 12.9) and HFS and DBS-OFF and LFS did not differ significantly (P > .05).ConclusionsHFS compared to LFS or DBS-OFF significantly reduced tremor but simultaneously worsened VF while working memory and cognitive inhibition remained unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data emphasize the relevance of thalamocortical loops for verbal fluency but also suggest that more sophisticated DBS-regimes in ET may improve both motor and cognitive performance.     

Acute response of non-motor symptoms to subthalamic deep brain stimulation in Parkinson's disease

BackgroundSubthalamic deep brain stimulation (STN-DBS) is an established treatment for the motor complications of Parkinson's disease (PD) and may have beneficial effects on non-motor symptoms (NMS). However, the acute effect of STN stimulation on NMS has only been explored in small PD cohorts with short post-surgical follow-up.ObjectiveTo study NMS response to an acute stimulation challenge in an STN-DBS PD population with a medium/long-term post-surgical follow-up.Methods32 STN-DBS PD patients were tested twice (MED OFF/STIM OFF and MED OFF/STIM ON). MDS-UPDRS-III, blood pressure (BP) assessment, a visual analogue scale for pain and fatigue and State Trait Anxiety Scale score were evaluated during both stimulation conditions. NMS were assessed with MDS-UPDRS-I, Non-Motor Symptoms Scale, Geriatric Depression Scale and the Neuropsychiatric Inventory scale.ResultsMean (SD) age was 62.5 (±13.3) years, mean disease duration 18.7 (±5.1) years, mean post-surgical follow-up 4.6 (±1.3) years, and the mean reduction of levodopa equivalent daily dose after surgery was 58.9% (±25.4%). Mean (SD) motor response to stimulation was 40% (15%). STN stimulation significantly improved anxiety (mean 18% ± 19%, P < 0.005) and fatigue (mean 25% ± 51%; P < 0.05), while pain, although improved did not reach statistical significance. With stimulation ON, BP significantly decreased during orthostatism (P < 0.05) and there was a significant increase in asymptomatic orthostatic hypotension (P < 0.05).ConclusionsAcute STN stimulation improves anxiety and fatigue but decreases orthostatic BP in PD, several years after surgery. These effects should be considered when assessing long-term effect of DBS.     

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson’s disease

Deep brain stimulation (DBS) has emerged as a viable therapy for Parkinson’s disease (PD). The impact of subthalamic nucleus (STN) lead placement (lateral versus medial) on motor outcome, however, has not been systematically evaluated. Forty-eight patients with PD underwent STN-DBS surgery and were evaluated postoperatively for 48 weeks for motor improvement as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (standardized motor examination) and levodopa equivalent daily dose (LEDD). Postoperative MRI was used to identify the location of the active stimulating contact and motor outcome was analyzed. STN-DBS was associated with significant improvement in motor outcome as determined by a reduction in the UPDRS part III subscore from 34.44 ± 1.29 at baseline to 18.76 ± 1.06 at end visit (p < 0.0001) and a reduction in LEDD from 1721 ± 152 mg/day at baseline to 1134 ± 119 mg/day at end visit (p = 0.0024). Patients with stimulating contacts in the medial STN compared to the lateral STN did not demonstrate any significant differences in motor outcome (UPDRS, p = 0.5811; LEDD, p = 0.7341). No significant differences were found in motor outcome between patients with STN stimulation compared to stimulation of surrounding fiber tracts (p = 0.80). No significant difference in stimulation voltage was noted with respect to lead location. Our study did not find a significant effect for the location of active contact and motor outcome neither within the subregions of the STN nor between the STN and surrounding fibers. Further research is needed to better understand the neurophysiological basis for these results.     

Advanced therapies in Parkinson’s disease: Long-term retrospective study

BackgroundLevodopa/carbidopa intestinal gel infusion (LCIG) and subthalamic nucleus deep brain stimulation (STN-DBS) are approved therapies for advanced Parkinson’s disease (PD) whose long-term comparability remains unclear.MethodsWe reviewed the 5-year data on activities of daily living (ADL) and motor complications (OFF time, dyskinesia duration, and dyskinesia severity), as measured by the Unified Parkinson Disease Rating Scale (UPDRS) section-II and section-IV (items 39, 32, and 33, respectively) in 60 PD patients exposed to STN-DBS (n = 20), LCIG (n = 20), and oral medical therapy (OMT) (n = 20) at similar baseline disability and cognitive state.ResultsSTN-DBS and LCIG showed a similar magnitude of deterioration in ADL (+6.1 vs. +5.7 UPDRS-II; p = 0.709), but lesser than with OMT (+13.7 UPDRS-II; p = 0.005). OFF time also improved to the same extent in STN-DBS and LCIG (−62% vs. −54.5%; p = 0.830), while worsened with OMT (+78.6%; p < 0.001). STN-DBS and LCIG yielded greater improvement on dyskinesia compared to OMT (dyskinesia duration: −66.1% vs. −9.0% vs. +24.2% [p = 0.001]; dyskinesia severity: −68.8% vs. −18.0% vs. +16.2% [p = 0.002]), with relative superiority of STN-DBS over LCIG (p = 0.004 for duration; p = 0.014 for severity). The annualized rate of complication was lower in STN-DBS vs. LCIG (0.13 vs. 0.68; p < 0.001) but not different between STN-DBS and OMT (0.13 vs. 0.10; p = 0.795).ConclusionsSTN-DBS and LCIG showed comparable efficacy in ADL and OFF time, superior to OMT. STN-DBS yielded greater improvement in dyskinesia and lower long-term rate of complications than LCIG.     

Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational,prospective study

BackgroundSeveral studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study.MethodsForty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test.ResultsThe following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006).ConclusionsWe observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.     

Dopaminergic and serotonergic alterations in plasma in three groups of dystonia patients

IntroductionIn dystonia, dopaminergic alterations are considered to be responsible for the motor symptoms. Recent attention for the highly prevalent non-motor symptoms suggest also a role for serotonin in the pathophysiology. In this study we investigated the dopaminergic, serotonergic and noradrenergic metabolism in blood samples of dystonia patients and its relation with (non-)motor manifestations.MethodsConcentrations of metabolites of dopaminergic, serotonergic and noradrenergic pathways were measured in platelet-rich plasma in 41 myoclonus-dystonia (M-D), 25 dopa-responsive dystonia (DRD), 50 cervical dystonia (CD) patients and 55 healthy individuals. (Non-)motor symptoms were assessed using validated instruments, and correlated with concentrations of metabolites.ResultsA significantly higher concentration of 3-methoxytyramine (0.03 vs. 0.02 nmol/L, p < 0.01), a metabolite of dopamine, and a reduced concentration of tryptophan (50 vs. 53 μmol/L, p = 0.03), the precursor of serotonin was found in dystonia patients compared to controls. The dopamine/levodopa ratio was higher in CD patients compared to other dystonia groups (p < 0.01). Surprisingly, relatively high concentrations of levodopa were found in the untreated DRD patients. Low concentrations of levodopa were associated with severity of dystonia (r_s = −0.3, p < 0.01), depression (r_s = −0.3, p < 0.01) and fatigue (r_s = −0.2, p = 0.04).ConclusionThis study shows alterations in the dopaminergic and serotonergic metabolism of patients with dystonia, with dystonia subtype specific changes. Low concentrations of levodopa, but not of serotonergic metabolites, were associated with both motor and non-motor symptoms. Further insight into the dopaminergic and serotonergic systems in dystonia with a special attention to the kinetics of enzymes involved in these pathways, might lead to better treatment options.     

Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease

BackgroundEffects on non-motor symptoms, mainly cognitive and psychiatric side effects, could influence the decision for either globus pallidus pars interna (GPi) or subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with Parkinson's disease (PD).Objective1) To compare cognitive and psychiatric outcomes 3 years after GPi DBS versus STN DBS, and 2) to report on occurrence of suicidal ideation, psychiatric diagnoses, social functioning, and marital satisfaction 3 years after DBS.MethodsPatients were randomized to receive GPi DBS (n = 65) or STN DBS (n = 63). Standardized assessments were performed at baseline, 1 year, and 3 years. We used linear mixed model analyses to investigate between-group differences on the Mattis Dementia Rating Scale (MDRS), neuropsychological tests, and psychiatric questionnaires 3 years after DBS.ResultsEighty-seven patients (68%) completed at least one neuropsychological test after 3 years. No significant between-group differences were found on the MDRS (p = 0.61), neuropsychological tests (p-values between 0.17 and 0.87), and psychiatric questionnaires (p-values between 0.23 and 0.88) 3 years after DBS. The Mini International Neuropsychiatric Interview did not indicate a substantial number of psychiatric diagnoses after 3 years. Social functioning and marital satisfaction were comparable in both groups.ConclusionsThree years after GPi DBS and STN DBS no pronounced between-group differences on measures of cognitive and psychiatric functioning could be demonstrated. Overall, cognitive and psychiatric outcome 3 years after DBS do not provide a clear direction for clinicians when considering which of these two surgical targets to choose.     

Glutathione relates to neuropsychological functioning in mild cognitive impairment

BackgroundMild cognitive impairment (MCI) represents an at-risk state for Alzheimer's disease in which underlying pathophysiological mechanisms could be delineated. Oxidative stress has been implicated in Alzheimer's disease and can be measured by levels of the antioxidant glutathione. This study aims to assess in vivo levels of glutathione via proton magnetic resonance spectroscopy in patients with MCI and to determine how glutathione relates to cognitive decline.MethodsFifty-four patients with MCI and 41 healthy control subjects underwent proton magnetic resonance spectroscopy in conjunction with medical, psychiatric, and neuropsychological assessments. The concentration of glutathione was measured in the anterior and posterior cingulate, and ratios of glutathione were calculated relative to creatine. Neuropsychological performance was assessed across the domains of processing speed, learning, memory, and executive functions.ResultsIn comparison with control subjects, patients with MCI had significantly elevated ratios of glutathione in the anterior (t = −2.2, P = .03) and posterior (t = −2.9, P = .005) cingulate. Higher levels of anterior cingulate glutathione were related to neuropsychological decrements on tests of executive functions. Elevated posterior cingulate glutathione was associated with poorer memory consolidation.ConclusionThis study has shown for the first time that MCI is associated with increased glutathione in the cingulate, which in turn relates to neuropsychological performance. This finding may be indicative of an early compensatory or neuroprotective response, and the role of glial cells and glutathione enzymes requires delineation. Longitudinal studies examining the utility of glutathione as a marker for cognitive decline are now required.     

Beneficial nonmotor effects of subthalamic and pallidal neurostimulation in Parkinson’s disease

BackgroundSubthalamic (STN) and pallidal (GPi) deep brain stimulation (DBS) improve quality of life, motor, and nonmotor symptoms (NMS) in advanced Parkinson’s disease (PD). However, few studies have compared their nonmotor effects.ObjectiveTo compare nonmotor effects of STN-DBS and GPi-DBS.MethodsIn this prospective, observational, multicenter study including 60 PD patients undergoing bilateral STN-DBS (n = 40) or GPi-DBS (n = 20), we examined PDQuestionnaire (PDQ), NMSScale (NMSS), Unified PD Rating Scale-activities of daily living, -motor impairment, -complications (UPDRS-II, –III, -IV), Hoehn&Yahr, Schwab&England Scale, and levodopa-equivalent daily dose (LEDD) preoperatively and at 6-month follow-up. Intra-group changes at follow-up were analyzed with Wilcoxon signed-rank or paired t-test, if parametric tests were applicable, and corrected for multiple comparisons. Inter-group differences were explored with Mann-Whitney-U/unpaired t-tests. Analyses were performed before and after propensity score matching which balanced out demographic and preoperative clinical characteristics. Strength of clinical changes was assessed with effect size.ResultsIn both groups, PDQ, UPDRS-II, -IV, Schwab&England Scale, and NMSS improved significantly at follow-up. STN-DBS was significantly better for LEDD reduction, GPi-DBS for UPDRS-IV. While NMSS total score outcomes were similar, explorative NMSS domain analyses revealed distinct profiles: Both targets improved sleep/fatigue and mood/cognition, but only STN-DBS the miscellaneous (pain/olfaction) and attention/memory and only GPi-DBS cardiovascular and sexual function domains.ConclusionsTo our knowledge, this is the first study to report distinct patterns of beneficial nonmotor effects of STN-DBS and GPi-DBS in PD. This study highlights the importance of NMS assessments to tailor DBS target choices to patients’ individual motor and nonmotor profiles.     

Emotional symptoms and cognitive function outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts and the volume of tissue activated

Background

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), that can improve patients' motor and non-motor symptoms. However, there are differences in the improvement of patients' emotional symptoms and cognitive function.

Objective

To investigate the impact of active contact location and the volume of tissue activated (VTA) on patients' emotional symptoms and cognitive function in STN-DBS in PD.

Methods

A total of 185 PD patients were included in this study. We evaluated them using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE) scales at the preoperative, 1- and 12-month postoperative time points. Leads were positioned in standard space using the Lead-DBS toolbox, and VTA was calculated for analysis.

Results

When the lead active contact was closer to the ventral side of the STN, the patients' HAM-A improvement rate was higher, and when the active contact was closer to the anterior and dorsal sides of the STN, the patients' MoCA improvement rate was higher. Stimulation of the sensorimotor zone was more favorable to the improvement of HAM-A and HAM-D in patients. And, the stimulation of the associative zone was more favorable to the improvement of MoCA in patients.

Conclusion

Our results provide evidence that the 12-month outcomes of cognitive function and emotional symptoms in PD patients with STN-DBS were closely related to the specific location of the active contacts in the STN and influenced by the VTA.     

Parkinson's disease patients with subthalamic stimulation and carers judge quality of life differently

BackgroundQuality of life (QoL) improves under subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD), whereas social functioning may be disrupted. This disruption could negatively influence the family dynamic, leading to different perceptions of the STN-DBS outcome by patients and caregivers.MethodsWe recruited 34 PD patients for this prospective, controlled trial, 28 of whom were examined preoperatively, three months and one year after STN-DBS surgery. The primary outcome was QoL. We compared the patients' ratings and caregivers' proxy QoL ratings. The secondary outcome was social functioning. Additionally, neurological, neuropsychiatric and cognitive domains were analyzed. Changes were analyzed with repeated-measures ANOVA. Regression analysis was used to determine the association between QoL and social functioning.ResultsPatients' QoL improved significantly under STN-DBS (p = .003). At baseline, patients' and caregivers' QoL ratings were similar. However, one year postoperatively, QoL ratings differed significantly (p = .010), whereby QoL was rated worse by caregivers. Social functioning was positively influenced during the first months postoperatively, but did not improve longitudinally. One year postoperatively, social functioning was significantly associated with QoL ratings (patients: p = .004, caregivers: p = .002). Motor scores significantly improved, whereas verbal fluency and apathy worsened.ConclusionsUnequal perception of QoL between patients and caregivers exists under STN-DBS. The fact that social functioning does not improve longitudinally is perhaps due to patient's higher levels of apathy and reduced motivation following surgery. Our findings stress the importance of considering caregiver's input in DBS patients' outcomes and the need for pre-operative preparation.     

Depression may negatively affect the change in freezing of gait following subthalamic nucleus stimulation in Parkinson's disease

ObjectiveTo assess the influence of preoperative depression on the change in freezing of gait (FOG) following subthalamic nucleus stimulation (STN-DBS) in patients with Parkinson's disease (PD).MethodsOne hundred and twelve PD patients were included who received bilateral STN-DBS. Of these, 33 had no preoperative depression (PD-ND) and the other 79 had preoperative depression (PD-D). Each PD-ND patient was matched with one PD-D patient by the propensity score for which sex, age at PD onset, disease duration, UPDRS-III score during off-medication state, levodopa-equivalent daily dose, and mini mental state examination were the independent variables. We compared both a FOG-questionnaire (FOG-Q) and the axial score from UPDRS-III between the two groups over 12-month follow-up.ResultsDuring the off-medication state, FOG-Q at 12-month was decreased with STN-DBS in both PD-ND (−52.9%, p < 0.001) and PD-D (−24.2%, p < 0.001) with a significant difference in the change of FOG in favor of PD-ND (p = 0.001). Similarly, there was an improvement in the axial score for both PD-ND (−66.1%, p < 0.001) and PD-D (−45.3%, p < 0.001) at 12-month with a significant difference between the groups. (p = 0.005). During the on-medication state, both the FOG-Q and axial score at 12-month were not improved with STN-DBS in the PD-ND and PD-D with no difference between the groups.ConclusionsOur findings suggest that preoperative depression negatively affects the outcome of FOG following STN-DBS in the off-medication state but not in the on-medication state.     

Sleep parameters associated with long-term outcome following subthalamic deep brain stimulation in Parkinson's disease

IntroductionWe aimed to investigate the effects of changes in sleep architecture on long-term clinical outcome in patients with Parkinson's disease (PD) who underwent deep brain stimulation of subthalamic nuclei (STN DBS).MethodsWe followed up eight PD patients before and three years after STN DBS surgery. In addition to clinical assessments, polysomnography (PSG) followed by multiple sleep latency tests was performed before and after STN DBS, while stimulator was ON and OFF.ResultsSubjective sleep latency was significantly decreased (P = 0.033) and sleep duration was increased (P = 0.041), as measured by Pittsburgh sleep quality index. Latency to REM sleep stage was shortened after surgery with STN DBS ON (P = 0.002). Index of central type of abnormal respiratory events was significantly increased while stimulator was ON (P = 0.034). Total number of major body movements was found to be increased when stimulator was turned OFF (P = 0.012). Among PSG data obtained during STN DBS ON, it was observed that duration of N3 sleep was negatively correlated with UPDRS scores at 1st (P = 0.038) and 3rd (P = 0.045) post-operative years. Among PSG variables during STN DBS OFF, durations of N3 sleep (P = 0.017) and REM sleep (P = 0.041) were negatively correlated with UPDRS scores at post-operative 1st year.ConclusionDisturbances in sleep architecture are associated with higher UPDRS scores and worse prognosis at 1st and 3rd post-operative years. Similar results obtained while stimulator was OFF at the end of 1st year support the presence of microlesion effect after STN DBS, which is probably not long lasting.     

Neuropsychological and psychiatric assessments following bilateral deep brain stimulation of the subthalamic nucleus in Japanese patients with Parkinson’s disease

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n = 13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at 1 and 6 months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the Verbal Fluency Test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p < 0.001) and HAM-A score (p = 0.004) showed significant improvement at 1 month post-surgery, but a significant decline was observed in the WCST total error (p = 0.005) and the semantic VFT score (p < 0.001). The phonetic VFT also showed a substantial decline (p = 0.015) at 1 month post-surgery. At 6 months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms.     

Correlations between cognitive performances and psychotic or schizotypal dimensions

ObjectiveTo test if specific correlations exist between cognitive measures and psychotic dimensions in schizophrenic subjects and if similar correlations, between cognition and schizotypal dimensions, are present in non-psychotic subjects.MethodsWe administered the same battery of cognitive tests (Source Monitoring, Verbal Fluency [VF] and Stroop tests) to schizophrenic subjects (N = 54), their first-degree relatives (N = 37) and controls (N = 41). Scores of negative, positive and disorganisation dimensions were derived from the Signs and Symptoms of Psychotic Illness scale in schizophrenic subjects, and from the Schizotypal Personality Questionnaire in relatives and controls.ResultsIn schizophrenic subjects, as hypothesised, the negative dimension correlated with performance on VF and disorganisation with performance in the Stroop test. The positive dimension did not correlate with any cognitive measure.With only one exception, the significant correlations observed in non-psychotic subjects did not match correlations seen in schizophrenic subjects. In non-psychotic subjects greater disorganisation was associated with more clustered words in VF suggesting that excessive automatic spreading of activation in semantic networks could underlie this dimension.ConclusionAs a whole, data lent partial support to our hypothesis of specific cognitive–clinical correlations in schizophrenic subjects but did not support the existence of similar correlations in non-psychotic subjects.