The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for ...creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus.
We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months.
Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval CI, 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months.
Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).
Aim
Impulse‐control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards ...reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder.
Methods
The effect of sexual cues on inhibition was measured with a novel erotic stop‐signal task under on and off dopaminergic medication. Task‐related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta‐burst stimulation (sham‐controlled) was applied over the pre‐supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition.
Results
Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre‐supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre‐supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre‐supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues.
Conclusion
This study, therefore, has identified a specific fronto‐striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression.
Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to dopaminergic treatment, especially treatment with dopamine agonists (DAs). ...However, patients with Parkinson's disease (PD) may experience enhanced creativity during DA therapy, often manifesting as newfound artistic pursuits. Though ICD is very well recognized in the literature, enhanced creativity remains underreported, probably because, unlike ICD, enhanced creativity is often positive and rarely disruptive for patients and relatives.
We studied 21 patients (20 patients with PD and one patient with restless-legs syndrome) with enhanced creativity. These individuals engaged in artistic activities after dopaminergic treatment; all but one were treated with DA (pramipexole, 14/21; ropinirole, 4/21; rotigotine 2/21).
Most patients preferred painting as their main activity, but many were engaged in several activities, usually in combination. We hypothesize that by facilitating a stimulating environment for parkinsonian patients, this positive phenomenon may present more frequently.
•Impulse control disorders (ICD) is frequently seen in parkinsonian patients under dopamine agonists.•Some parkinsonian patients, however, develop enhanced creativity under dopamine agonists.•This dopaminergic-related enhanced creativity is usually positive and non disruptive for patients and families.•Probably a rich environment may stimulate some patients to develop enhanced creativity instead ICD.
Abstract
BACKGROUND
Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients.
OBJECTIVE
...To provide a comprehensive characterization of the radiological, topographical, and volumetric aspects of the tcMRgFUS thalamic lesion, and to quantify how they relate to the clinical outcomes.
METHODS
In this study, clinical and radiological data from forty patients with medically-refractory essential tremor treated with unilateral tcMRgFUS thalamotomy were retrospectively analyzed. Treatment efficacy was assessed with Clinical Rating Scale for Tremor (CRST). Lesions were manually segmented on T1, T2, and susceptibility-weighted images, and 3-dimensional topographical analysis was then carried out. Statistical comparisons were performed using nonparametric statistics.
RESULTS
The greatest clinical improvement was correlated with a more inferior and posterior lesion, a bigger lesion volume, and percentage of the ventral intermediate nucleus covered by the lesion; whereas, the largest lesions accounted for the occurrence of gait imbalance. Furthermore, the volume of the lesion was significantly predicted by the number of sonications surpassing 52°C.
CONCLUSION
Here we provide a comprehensive characterization of the thalamic tcMRgFUS lesion including radiological and topographical analysis. Our results indicate that the location and volume of the lesion were significantly associated with the clinical outcome and that mid-temperatures may be responsible for the lesion size. This could serve ultimately to improve targeting and judgment and to optimize clinical outcome of tcMRgFUS thalamotomy.
ABSTRACT
Background
Dopamine replacement therapy reduces most motor and nonmotor features of Parkinson's disease. However, with disease progression, adjustments of dopaminergics and the application ...of advanced therapies must be considered.
Objectives
To validate the OPTIMIPARK questionnaire as a tool to help clinicians make therapeutic decisions on patients treated with levodopa.
Methods
We tested a questionnaire including 9 items encompassing motor and nonmotor signs, complications, and disability in a multicenter, observational, cross‐sectional study. A neurologist (neurologist 1 N1) assessed patients according to regular clinical practice and blinded to the OPTIMIPARK questionnaire score. Therapeutic decisions were classified as “no changes,” “adjustment of conventional treatment,” and “advanced therapy indicated.” External neurologists (neurologist 3 N3 and neurologist 4 N4), who only knew the patient age, years of disease, and current treatment, made their therapeutic decisions based on the OPTIMIPARK score. Concordance between the criterion of the N1 versus the OPTIMIPARK‐based N3–N4 consensus was analyzed applying weighted κ. The area under Receiving Operating Characteristic (ROC) curves was calculated for OPTIMIPARK scores.
Results
A total of 113 patients with Parkinson's disease were included. The OPTIMIPARK‐based decision led to a higher proportion of patients requiring therapeutic modification than N1 assessment (74% vs. 60%; P = 0.002). Concordance between the N1 and N3–N4 decisions was moderate, whereas interobserver agreement among N3 and N4 was high. Area Under the Curve(AUC) values of 0.83 and 0.82 were found for “no changes” and “advanced therapy indicated” decisions by the N1 neurologist.
Conclusions
OPTIMIPARK might be more sensitive than regular clinical practice in suggesting the need for a therapeutic change. Furthermore, the low and high scores identify with high accuracy well‐adjusted patients and candidates for advanced therapy, respectively.
People with Parkinson's disease (PD) present deficits of the active range of motion (ROM), prominently in their trunk. However, if these deficits are associated with axial rigidity, the functional ...mobility or health related quality of life (HRQoL), remains unknown. The aim of this paper is to study the relationship between axial ROM and axial rigidity, the functional mobility and HRQoL in patients with mild to moderate PD.
An exploratory study was conducted. Non-probabilistic sampling of consecutive cases was used. Active trunk ROM was assessed by a universal goniometer. A Biodex System isokinetic dynamometer was used to measure the rigidity of the trunk. Functional mobility was determined by the Get Up and Go (GUG) test, and HRQoL was assessed with the PDQ-39 and EuroQol-5D questionnaires.
Thirty-six mild to moderate patients with PD were evaluated. Significant correlations were observed between trunk extensors rigidity and trunk flexion and extension ROM. Significant correlations were observed between trunk flexion, extension and rotation ROM and GUG. Moreover, significant correlations were observed between trunk ROM for flexion, extension and rotations (both sides) and PDQ-39 total score. However, these correlations were considered poor.
Trunk ROM for flexion and extension movements, measured by a universal goniometer, were correlated with axial extensors rigidity, evaluated by a technological device at 30°/s and 45°/s, and functional mobility. Moreover, trunk ROM for trunk flexion, extension and rotations were correlated with HRQoL in patients with mild to moderate PD.
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