Voice acoustic changes during bilateral subthalamic stimulation in patients with Parkinson's disease

Objectives

The purpose of this study was to investigate the effects of bilateral subthalamic nucleus deep brain stimulation on the phonation of patients with Parkinson's disease in three drug-free conditions: (1) stimulation off, (2) with clinically optimised stimulation parameters, and (3) subthreshold overstimulation, in order to detect differences following voice analysis.

Patients and methods

Conversational speech and sustained vowel sounds /a/, /i/, /o/, /u/ and high /i/ were recorded from 22 PD patients. Perceptual analysis, perturbation jitter, shimmer, noise-to-harmonics ratio, and nonlinear dynamic analysis (NDA) with detrended fluctuation analysis and recurrence period density entropy were measured and compared to the above conditions. Quadratic discriminant analysis (QDA) was used to investigate stimulation conditions for given acoustic data.

Results

The changes of perturbation measurements for the above conditions were not significant. With differences between vowels, NDA showed more significant changes and more powerful correlation with perceptual scores than perturbation measurements. NDA was significantly more sensitive during the QDA of the conditions.

Conclusions

Acoustic voice analysis of sustained vowels can help with recognizing the overstimulated condition, and, with an appropriate test battery and software package including nonlinear dynamic analysis, it can be a valuable tool for fine adjustments of stimulation parameters.     

Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson's disease: a prospective case-control study

Background

High-frequency stimulation of the subthalamic nucleus (STN-DBS) improves motor symptoms in advanced Parkinson's disease (PD), but the mechanisms are still unclear. Functional imaging evidenced pathological overactivity in motor cortical areas in advanced PD that can be normalized by effective therapies.

Patients and methods

We studied resting state cerebral blood flow pre-operatively and 12 months after surgery in 40 patients with advanced PD using ECD-SPECT. SPECT scans were also acquired 1 year apart in 21 matched PD controls who did not undergo surgery. Statistical analysis was performed using statistical parametric mapping (SPM2) software. In addition, we correlated brain perfusion changes after surgery with clinical improvement, assessed using the unified PD rating scale motor score (UPDRS-III).

Results

Patients showed marked motor improvement and medication reduction after surgery. Stimulated PD patients revealed bilateral rCBF decrements in motor cortical areas and prefrontal cortex bilaterally compared to pre-surgical condition as well as versus PD controls (p < .01 FDR corrected). Perfusion increases were found in cerebellum, temporal and occipital lobes. Clinical improvement was associated with perfusion decrements in primary motor and premotor cortices.

Conclusions

Effective STN-DBS is associated with neuronal activity changes in brain regions implicated in movement programming and performance. We hypothesize that clinical benefit might be associated with stimulation-induced normalization of the abnormal overactivity within the cortico-basal ganglia-thalamo-cortical motor loop in advanced PD.     

Therapeutic high-frequency stimulation of the subthalamic nucleus in Parkinson's disease produces global increases in cerebral blood flow

Chronic, high-frequency electrical stimulation of the subthalamic nuclei (STNs) has become an effective and widely used therapy in Parkinson's disease (PD), but the therapeutic mechanism is not understood. Stimulation of the STN is believed to reorganize neurophysiological activity patterns within the basal ganglia, whereas local field effects extending to tracts adjacent to the STN are viewed as sources of nontherapeutic side effects. This study is part of a larger project investigating the effects of STN stimulation on speech and regional cerebral blood flow (CBF) in human subjects with PD. While generating measures of global CBF (gCBF) to normalize regional CBF values for a subsequent combined analysis of regional CBF and speech data, we observed a third effect of this therapy: a gCBF increase. This effect was present across three estimates of gCBF ranging from values based on the highest activity voxels to those based on all voxels. The magnitude of the gCBF increase was related to the subject's duration of PD. It is not clear whether this CBF effect has a therapeutic role, but the impact of deep brain stimulation on cerebrovascular control warrants study from neuroscience, pathophysiological, and therapeutic perspectives.     

Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: A [15O] H2O PET study

Patients with advanced Parkinson's disease (PD) develop disabling axial symptoms, including gait disturbances, freezing and postural instability poorly responsive to levodopa replacement therapy. The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement sleep]. Recent reports suggested that PPN modulation with deep brain stimulation (DBS) may be beneficial in the treatment of axial symptoms. However, the mechanisms underlying these effects are still unknown. We used [¹⁵O] H₂O PET to investigate regional cerebral blood flow in three patients with advanced PD who underwent a new experimental surgical procedure with implantation of unilateral PPN‐DBS. Patients were studied Off‐medication with stimulator Off and On, both at rest and during a self‐paced alternating motor task of the lower limbs. We used SPM2 for imaging data analysis, threshold P < 0.05 corrected at the cluster level. Stimulation induced significant regional cerebral blood flow increment in subcortical regions such as the thalamus (P < 0.006), cerebellum (P < 0.001), and midbrain region (P < 0.001) as well as different cortical areas involving medial sensorimotor cortex extending into caudal supplementary motor area (BA 4/6; P < 0.001). PPN‐DBS in advanced PD resulted in blood flow and presumably neuronal activity changes in subcortical and cortical areas involved in balance and motor control, including the mesencephalic locomotor region (e.g. PPN) and closely interconnected structures within the cerebello‐(rubro)‐thalamo‐cortical circuit. Whether these findings are associated with the DBS‐PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Bilateral subthalamic nucleus stimulation for Parkinson's disease

High frequency stimulation of the subthalamic nucleus (STN) is known to ameliorate the signs and symptoms of advanced Parkinson's disease. AIM: We studied the effect of high frequency STN stimulation in 23 patients. METHOD: Twenty-three patients suffering from severe Parkinson's disease (Stages III-V on Hoehn and Yahr scale) and, particularly bradykinesia, rigidity, and levodopa-induced dyskinesias underwent bilateral implantation of electrodes in the STN. Preoperative and postoperative assessments of these patients at 1, 3, 6 and 12 months follow-up, in "on" and "off" drug conditions, was carried out using Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging, England activities of daily living score and video recordings. RESULTS: After one year of electrical stimulation of the STN, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III) off medication improved by 62% and 61% respectively (p<0.0005). The subscores for the akinesia, rigidity, tremor and gait also improved. (p<0.0005). The average levodopa dose decreased from 813 mg to 359 mg. The cognitive functions remained unchanged. Two patients developed device-related complications and two patients experienced abnormal weight gain. CONCLUSION: Bilateral subthalamic nucleus stimulation is an effective treatment for advanced Parkinson's disease. It reduces the severity of "off" phase symptoms, improves the axial symptoms and reduces levodopa requirements. The reduction in the levodopa dose is useful in controlling drug-induced dyskinesias.     

Cerebral blood flow changes induced by CO2 in anxiety

Cerebral blood flow (CBF) was measured twice with the 133Xenon inhalation technique, under resting conditions and during 5% CO2 inhalation, in 13 patients with generalized anxiety disorder and a group of normal volunteers of comparable age and sex distribution. CO2 inhalation was associated with similar increases in end-tidal CO2 (PECO2) and CBF. Neither group showed statistically significant increases in state anxiety. However, when subjects (both patients and controls) who became anxious during CO2 inhalation were compared with those who did not, on associated CBF changes, significant differences emerged. The former showed less marked CBF increase as compared to the latter in the absence of any significant differences between the two groups on PECO2 during the second measurement. Changes in state anxiety and CBF showed a statistically significant inverse correlation for the entire group.     

Cerebral blood flow and cognitive impairment in Parkinson's disease

In Parkinson's disease, there is high prevalence of dementia, reduction of the regional cerebral blood flow (rCBF), and neuronal loss and Alzheimer-like pathologic changes in cerebral cortex. Since rCBF is also decreased in Alzheimer's dementia, it is theoretically possible that both decreases in rCBF and cognitive impairment in parkinsonians are caused by a similar mechanism, eg, reduced metabolic demand or loss of cholinergic neurons innervating cortex and microvessels. We therefore measured rCBF using the 133Xenon inhalation technique and evaluated cognitive function with a detailed neuropsychological test battery in 48 patients with Parkinson's disease. Mean brain, hemispheric, and regional flows were decreased in parkinsonians as compared with those in age-matched controls. Most of the cognitive functions were impaired in patients as compared with those in normal subjects. However, there was no correlation between the magnitude of rCBF reduction and the presence and severity of intellectual deterioration in parkinsonians, suggesting that each may be caused by a different mechanism.     

Cerebral blood flow and dementia in Parkinson's disease.

Regional cerebral blood flow (CBF) was examined in 27 patients with Parkinson's disease using single-photon emission computed tomography and N-isopropyl-p-[123I]iodoamphetamine as a tracer. Their CBF pattern was compared with that of seven patients with Alzheimer's disease and nine age-matched neurologically normal controls. Tracer activity was determined in seven bilateral cerebellar, cortical, and subcortical regions and was expressed as the ratio of activity in each region to the mean tracer activity in the cerebellar region. Nineteen patients with nondemented Parkinson's disease showed significantly decreased tracer activity ratio in the frontal and temporal cortices, basal ganglia, and thalamus compared with that in controls. The eight demented Parkinson's disease patients showed significantly decreased tracer activity ratio in the temporal and parietal cortices compared with the patients without dementia, and demonstrated CBF pattern similar to that of patients with Alzheimer's disease. These findings suggest that in patients with Parkinson's disease, the mechanism of CBF reduction of the frontal cortical region differs from that in the temporoparietal cortical region and support the concept that Parkinson's disease and Alzheimer's disease may overlap in some patients.     

Fear recognition is impaired by subthalamic nucleus stimulation in Parkinson's disease

Behavioural disturbances such as disorders of mood, apathy or indifference are often observed in Parkinson's disease (PD) patients with chronic high frequency deep brain stimulation of subthalamic nucleus (STN DBS). Neuropsychological modifications causing these adverse events induced by STN DBS remain unknown, even if limbic disturbances are hypothesised. The limbic system supports neural circuits processing emotional information. The aim of this work is to evaluate changes of emotional recognition in PD patients induced by STN DBS. Thirty PD patients were assessed using a computerised paradigm of recognition of emotional facial expressions [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto, CA: Consulting Psychologists Press], 15 before STN DBS and 15 after. The two patients groups were compared to a group of 15 healthy control subjects. One series of 55 pictures of emotional facial expressions was presented to each patient. Patients had to classify the pictures according to seven basic emotions (happiness, sadness, fear, surprise, disgust, anger and no emotion). The intact ability to percept faces was firstly assured using the Benton Recognition Test. Recognition of fear expressions was significantly and selectively reduced in the post-operative group in comparison to both pre-operative and control groups. Our results demonstrate for the first time a selective reduction of recognition of facial expressions of fear by STN DBS. This impairment could be the first neuropsychological marker of a more general limbic dysfunction, thought to be responsible for the behavioural disorders reported after STN DBS.     

Neuro-psychiatric therapy during chronic subthalamic stimulation in Parkinson's disease

BackgroundNeuro-psychiatric (NP) disturbances are highly prevalent in patients with Parkinson's disease (PD) and contribute to worsen quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly utilized as surgical treatment for advanced PD with motor complications. The effectiveness of the procedure on motor symptoms is well established whereas the effects of STN-DBS on NP symptoms are less clear. The aim of our study was to analyze the postoperative pharmacological therapy for NP symptoms in a group of STN-DBS treated PD patients. Such therapy provides indirect information about the evolution of underlying NP disturbances during the follow-up in this group of PD patients.MethodsNP therapy (benzodiazepines, antidepressants, antipsychotics) was assessed in 48 consecutive PD patients treated by STN-DBS, preoperatively and postoperatively after 4 months, 1 year and 3 years. Motor symptoms were evaluated by the Unified PD Rating Scale (UPDRS) and levodopa equivalence daily dose (LEDD) was calculated. Cognitive, mood and anxiety assessments were performed with appropriate rating scales.ResultsThe number of patients treated with antidepressant drugs gradually increased during the follow-up. The use of antipsychotic drugs was stable until 1 year, with a subsequent increase at 3 years. Benzodiazepines were given to fewer patients immediately after surgery.ConclusionsPharmacological treatment supplies further information about NP symptoms in the follow-up of PD patients undergoing STN stimulation.     

Sleep apnea syndrome and subthalamic stimulation in Parkinson's disease

ObjectivesΤhe association between Parkinson's disease (PD) and sleep apnea syndrome (SAS) is not fully elucidated and very few studies reported on SAS outcome after deep brain stimulation (DBS). Here, we compare the clinical profile of PD patients with and without SAS and assess, for the first time, the value of pre-DBS SAS as predictor of post-DBS outcome in PD.MethodsFifty patients were grouped into PD with SAS (PD-SAS+,n = 22) and without (PD-SAS-,n = 28), based on the Apnea-Hypopnea-Index (AHI≥5) in polysomnography. We used novel multivariate statistical models to compare pre-DBS profiles and assess post-DBS motor, non-motor and quality of life (QoL) changes in both groups.ResultsIn the entire cohort, 44% of patients had at least mild SAS (AHI≥5), while 22% had at least moderate (AHI≥15). Mean AHI was 11/h (NREM-AHI = 10.2/h and REM-AHI = 13.5/h). The two groups had equal demographics and PD characteristics, and did not differ in respect to unified Parkinson's disease rating scale (UPDRS)-II_OFF, Body-Mass-Index, polysomnographic features, RBD, depression, sleepiness and QoL scores. The PD-SAS+ group had significantly higher scores in UPDRS-III_OFF (41.1 ± 17.7 vs. 30.9 ± 11.7,p < 0.05) compared to PD-SAS- group.The groups did not differ in respect to post-DBS change in UPDRS-II, UPDRS-III, Epworth sleepiness scale, Hamilton depression rating scale and PDQ39 scores. Positive airway pressure therapy had no impact on post-DBS outcome.ConclusionsIn patients with PD and candidates for DBS, the presence of SAS is associated with increased motor signs, but not with a specific non-motor, QoL or sleep-wake profile. The presence of SAS prior to STN-DBS is not associated with worse outcome after surgery.     

Unilateral subthalamic stimulation for early-stage Parkinson's disease]

According to evidenced-based criteria, surgical treatment with subthalamic stimulation is indicated for advanced Parkinson's disease with severe motor complications. Currently, the treatment is indicated for patients in whom medical treatment has failed even if the patient is still in an early stage. This study investigated the efficacy and safety of unilateral subthalamic stimulation for patients with early-stage Parkinson's disease. We evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) and the Schwab England ADL score before and 6 months after this treatment in 6 patients with early-stage Parkinson's disease demonstrating predominantly unilateral parkinsonian symptoms. We implanted a stimulation electrode (model 3387 or 3389) unilaterally on the side showing dominate symptoms, using both MRI and electrophysiological guidance. Six months after the beginning of stimulation, the UPDRS motor score without medication was improved by 64% and the Schwab England ADL score was improved by 23%. There were no adverse events except for asymptomatic intra-ventricular hemorrhage in one patient. Unilateral subthalamic stimulation is a useful treatment for patients with early-stage Parkinson's disease showing predominantly unilateral parkinsonian symptoms. However, long-term results of subthalamic stimulation for early-stage patients remain unclear.     

Behavioural disorders,Parkinson's disease and subthalamic stimulation

OBJECTIVE: to analyse 24 parkinsonian patients successfully treated by bilateral STN stimulation for the presence of behavioural disorders. METHOD: patients were evaluated retrospectively for adjustment disorders (social adjustment scale, SAS), psychiatric disorders (comparison of the results of psychiatric interview and the mini international neuropsychiatric inventory) and personality changes (IOWA scale of personality changes). RESULTS: parkinsonian motor disability was improved by 69.5% and the levodopa equivalent daily dosage was reduced by 60.5%. Social adjustment (SAS) was considered good or excellent in nine patients, moderately (n=14), or severely (n=1) impaired in 15 patients. Psychiatric disorders consisted of amplification or decompensation of previously existing disorders that had sometimes passed unnoticed, such as depressive episodes (n=4), generalised anxiety (n=18), and behavioural disorders with drug dependence (n=2). Appearance of mild to moderate emotional hyperreactivity was reported in 15 patients. Personality traits (IOWA scale) were improved in eight patients, unchanged in seven, and aggravated in eight CONCLUSION: Improvement in parkinsonian motor disability induced by STN stimulation is not necessarily accompanied by improvement in psychic function and quality of life. Attention is drawn to the possible appearance of personality disorders and decompensation of previous psychiatric disorders in parkinsonian patients who are suitable candidates for neurosurgery. We suggest that a careful psychological and psychiatric interview be performed before surgery, and emphasise the need for psychological follow up to ensure the best possible outcome.     

Language recovery following subthalamic nucleus stimulation in Parkinson's disease

Neuropsychological consequences of stimulation of the subthalamic nucleus for treatment of drug-resistant Parkinson's disease (PD) have been studied previously. However, no detailed investigations of linguistic function modifications have been carried out. We studied four consecutive patients with PD who underwent chronic bilateral stimulation of the subthalamic nuclei. Neuropsychological and linguistic evaluations were performed before and 2 weeks after surgery. Linguistic abilities were studied also 1 year after surgery with stimulators both off and on. Intraphrasal hesitation pauses, phonemic paraphasias and morpho-syntactic errors were significantly reduced and lexical retrieval improved with stimulation of the subthalamic nuclei. Implicit linguistic phenomena, mainly occurring within basal ganglia circuitry, benefited by recovery of functional equilibrium within basal nuclei and between overall basal ganglia circuitry and cerebral cortex.     

Deep brain stimulation of subthalamic nucleous in Parkinson's disease

We present the preliminary results in patients well selected to be implanted by deep brain stimulation (DBS) for Parkinsons's disease (PD). METHODS: 8 PD patients with disabled tremor, akinetic/bradikinetic and rigidity, in spite of best therapeutic assay with poor response were referred to surgery. It was implanted DBS Itrell 2. Theses patients were evaluated by the following scales: UPDRS, Schwab and England. RESULTS: The preliminary results in 6 months showed significant improvement of motor performance and it is shown by the scores. There were no complications so far with these procedures. CONCLUSION: The preliminary results indicate that DBS is highly effective, with benefit to those patients and it is according to literature.