Asymmetric Parkinson's Disease Research Articles

Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease

Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with PD who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication. Staged bilateral FUS-STN. Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson's Disease Questionnaire), change in dopaminergic treatment, patient's global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients' median duration of disease was 5.7 years (IQR, 4.7-7.3 years). The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioral or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Arm Swing while Walking and Running: A New Clinical Feature to Separate Parkinson's Disease from Functional Parkinsonism.

Functional parkinsonism is an important differential diagnosis of Parkinson's disease (PD). Based on anecdotal experience, we hypothesized that arm swing while walking and running could differentiate these two conditions, but this assumption has not been previously explored systematically. To examine differences in arm swing while walking and running between patients with PD and functional parkinsonism. We analyzed blinded video assessments of arm swing and other gait parameters in patients with asymmetrical PD (n = 81) and functional parkinsonism (n = 8) while walking and running. The groups were matched for age, sex and disease duration. In contrast to those with PD, patients with functional parkinsonism (i) were more likely to have a marked asymmetry in arm swing while walking (5/8 vs. 25/81; P = 0.06), (ii) were less likely to improve arm swing while running with full effort (3/8 vs. 72/81; P < 0.001) and (iii) demonstrated normal passive arm swing even when asymmetry of arm swing was marked during running/walking (6/6 vs. 9/33; P = 0.002). Assessment of arm swing while walking and running and passive arm swing could be important differentiating clinical features between functional parkinsonism and PD.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Asymmetry of Periodic Leg Movements in Sleep (PLMS) in Parkinson's Disease.

Periodic limb movements in sleep (PLMS) are repetitive movements usually of the legs strongly associated with Restless-legs syndrome (RLS), which appear more frequently in males, older age and other sleep disturbances, such as sleep-disordered breathing (SDB). Patients with Parkinson's disease (PD) suffer from various sleep disturbances including REM sleep behavior disorder, RLS and PLMS. Although a dopaminergic pathophysiology of PLMS is discussed, no systematic data on PLMS side-to-side distribution in PD and its correlation with asymmetry of motor symptoms are available. This study aimed at elucidating PLMS asymmetry in correlation to that of motor symptoms in PD compared to SDB and RLS. Cross-sectional, retrospective analysis of two polysomnography (PSG) recordings per patient scoring PLMS separately for both legs. Of 105 patients (44 PD, 44 age- and sex-matched SDB and 17 RLS patients) PLMS measures (number of PLM, PLM-Index, PLM-arousal index) showed significant side-to-side differences in all disease entities in both PSGs (P < 0.001; Wilcoxon rank test). PLM-Index asymmetry (PLM-I difference of >5/h between both sides) was observed less frequently in PD (34% of patients) compared to RLS (77% , P < 0.05) and SDB (59% , P < 0.05; χ2 test). In asymmetric PD patients, predominant side of PLMS was more stable than in SDB and RLS comparing the two PSGs, but we did not detect an agreement between PLMS predominant side with that of motor symptoms in PD patients. Only the minority of PD patients shows asymmetric PLMS distribution with relatively high night-to-night stability but no correlation with motor symptom asymmetry.

Quantitative Research of 11C-CFT and 18F-FDG PET in Parkinson's Disease: A Pilot Study With NeuroQ Software.

Dopamine transporter (DAT) and glucose metabolism imaging have been applied in the diagnosis of Parkinson’s disease (PD). We explored the possibility of evaluating for PD with NeuroQ software by analyzing 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-FDG PET/CT. We retrospectively analyzed brain 11C-CFT and 18F-FDG PET/CT of 38 patients with parkinsonism, including 20 with PD, 10 with multiple system atrophy (MSA) and 8 with essential tremor (ET), and compared them with the PET/CT of 11 normal healthy controls (NC). PD patients were divided into mild and moderate-severe grade according to the Hoehn-Yahr (H&Y) scale. The 11C-CFT uptake in the caudate nuclei (CN) and putamen (Pu) normalized with cerebellum (CN/Cb and Pu/Cb) were obtained with a manual method and NeuroQ software, and their diagnostic performance was compared.18F-FDG uptake of specific regions was also obtained with NeuroQ, and the enhancement effect for the differential diagnosis was evaluated. There was significant agreement between the manual method and the NeuroQ method for 11C-CFT uptake by CN (r2= 0.680) and Pu (r2= 0.770). 11C-CFT uptake by CN and Pu in PD and MSA patients was significantly lower compared to NC and ET patients. The cutoffs of CN/Cb and Pu/Cb for the distinction between PD and NC were 1.71 and 2.20, respectively. No difference in uptake ratios occurred between PD and MSA. 18F-FDG uptake by the pons and cerebellum in the MSA group was markedly decreased. It was highly accurate in distinguishing between PD and MSA when combined with analysis of 11C-CFT uptake. Pu/Cb decreased significantly in mild grade PD compared to NC group (1.92 ± 0.33 vs. 2.82 ± 0.43); however no statistically significant decrease in CN/Cb was observed until moderate-severe grade PD (1.43 ± 0.11 vs. 2.23 ± 0.36). In early asymmetric PD, a statistically significant difference could be seen with Pu/Cb between the symptomatic and asymptomatic side (2.17 ± 0.30 vs. 1.95 ± 0.22). 11C-CFT and 18F-FDG PET/CT can be analyzed quantitatively with NeuroQ software, which provides an accurate method for the diagnosis and severity evaluation of PD.

Hemispheric specialization of the basal ganglia during vocal emotion decoding: Evidence from asymmetric Parkinson's disease and 18FDG PET

The possible hemispheric specialization of the basal ganglia during emotional prosody (i.e., vocal emotion) processing has still to be elucidated. Coupled with affective measures and neuroimaging, Parkinson's disease offers a unique opportunity to study this question, on account of its characteristically asymmetric striatal dysfunction, which translates into predominantly contralateral motor symptoms. We investigated the cerebral metabolic bases of emotional prosody recognition in patients with Parkinson's disease with left- versus right-lateralized motor symptoms, postulating that patients with greater right hemispheric brain dysfunction have a specific impairment that correlates with the metabolic modification of a brain network known to be involved in emotional prosody. A total of 38 patients performed a validated emotional prosody recognition task and underwent a resting-state F-18 fluorodeoxyglucose PET scan, as well as clinical, motor, neuropsychological, and psychiatric assessments. Patients’ performances were compared with those of 45 healthy controls. As expected, vocal emotion recognition was significantly poorer among patients with left-sided motor symptoms than among both right-sided patients and controls. There was no significant difference between right-sided patients and controls. This effect was observed for both the total score and the happiness subscore. Interestingly, regressions showed that the greater the emotional misattribution, the greater the patients’ age and asymmetric motor symptom severity. Finally, at the metabolic level, positive correlations were found between the happiness recognition subscore and the metabolism of the right orbitofrontal cortex in patients with left-sided motor symptoms. A right orbitofrontal-basal ganglia coupling seems to be specifically involved in the vocal emotion recognition deficit observed in Parkinson's disease. The asymmetry of motor symptoms is thus an important clinical factor, in that it may influence the presence or severity of affective disorders in Parkinson's disease.

Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study

Ablative neurosurgery has been used to treat Parkinson's disease for many decades. MRI-guided focused ultrasound allows focal lesions to be made in deep brain structures without skull incision. We investigated the safety and preliminary efficacy of unilateral subthalamotomy by focused ultrasound in Parkinson's disease. This prospective, open-label pilot study was done at CINAC (Centro Integral de Neurociencias), University Hospital HM Puerta del Sur in Madrid, Spain. Eligible participants had Parkinson's disease with markedly asymmetric parkinsonism. Patients with severe dyskinesia, history of stereotactic surgery or brain haemorrhage, a diagnosis of an unstable cardiac or psychiatric disease, or a skull density ratio of 0·3 or less were excluded. Enrolled patients underwent focused ultrasound unilateral subthalamotomy. The subthalamic nucleus was targeted by means of brain images acquired with a 3-Tesla MRI apparatus. Several sonications above the definitive ablation temperature of 55°C were delivered and adjusted according to clinical response. The primary outcomes were safety and a change in the motor status of the treated hemibody as assessed with part III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) in both off-medication and on-medication states at 6 months. Adverse events were monitored up to 48 h after treatment and at scheduled clinic visits at 1, 3, and 6 months after treatment. The study is registered with ClinicalTrials.gov, number NCT02912871. Between April 26 and June 14, 2016, ten patients with markedly asymmetric parkinsonism that was poorly controlled pharmacologically were enrolled for focused ultrasound unilateral subthalamotomy. By 6 months follow-up, 38 incidents of adverse events had been recorded, none of which were serious or severe. Seven adverse events were present at 6 months. Three of these adverse events were directly related to subthalamotomy: off-medication dyskinesia in the treated arm (one patient, almost resolved by 6 months); on-medication dyskinesia in the treated arm (one patient, resolved after levodopa dose reduction); and subjective speech disturbance (one patient). Four of the adverse events present at 6 months were related to medical management (anxiety and fatigue [one patient each] and weight gain [two patients]). The most frequent adverse events were transient gait ataxia (related to subthalamotomy, six patients), transient pin-site head pain (related to the head frame, six patients), and transient high blood pressure (during the procedure, five patients). Transient facial asymmetry (one patient) and moderate impulsivity (two patients) were also recorded. The mean MDS-UPDRS III score in the treated hemibody improved by 53% from baseline to 6 months in the off-medication state (16·6 [SD 2·9] vs 7·5 [3·9]) and by 47% in the on-medication state (11·9 [3·1] vs 5·8 [3·5]). MRI-guided focused ultrasound unilateral subthalamotomy was well tolerated and seemed to improve motor features of Parkinson's disease in patients with noticeably asymmetric parkinsonism. Large randomised controlled trials are necessary to corroborate these preliminary findings and to assess the potential of such an approach to treat Parkinson's disease. Fundación de investigación HM Hospitales and Insightec.

Effects of More-Affected vs. Less-Affected Motor Cortex tDCS in Parkinson's Disease.

Objective: To evaluate therapeutic potential of different montages of transcranial direct current stimulation (tDCS) in Parkinson’s Disease (PD) patients with asymmetric motor symptoms.Materials and Methods: Fourteen patients with asymmetric PD underwent, while on treatment, seven separate sessions including electrophysiological and clinical evaluation at baseline and after anodal, cathodal and sham tDCS of the primary motor cortex (M1) of the two hemispheres. Changes in motor cortical excitability were evaluated by transcranial magnetic stimulation (TMS). Effects on motor symptoms were assessed by testing finger tapping (FT) and upper limb bradykinesia, and by using the Italian validated Movement Disorder Society revision of the Unified PD Rating Scale (MDS-UPDRS).Results: Only anodal tDCS of the more-affected M1 (contralateral to the more-affected body side) and cathodal tDCS of the less-affected M1 (contralateral to the less-affected body side) were able to induce significant changes in cortical excitability, i.e., facilitation and inhibition of the motor evoked potentials respectively. The motor performances of both hands significantly improved after anodal tDCS of the more-affected M1, as well as after cathodal tDCS of the less-affected one.Conclusion: Our findings support the potential usefulness of tDCS as add-on treatment for asymmetric PD, also providing interesting clues on the possible pathophysiological role played by an asymmetric activation of homologous motor cortical areas in PD.

Unilateral Subthalamic Nucleus Stimulation in the Treatment of Asymmetric Parkinson"s Disease with Early Motor Complications.

The aim of this study was to assess the results of unilateral subthalamic nucleus (STN) stimulation for the treatment of Parkinson"s disease (PD) with marked asymmetry of parkinsonian motor symptoms and early motor complications. The clinical series consisted of 32 consecutive PD patients, in whom unilateral STN stimulation was performed. All patients were assessed according to the Unified Parkinson"s Disease Rating Scale (UPDRS), and Hoehn and Yahr staging. The patients were assessed preoperatively, and at 12, and 24 months after unilateral STN stimulation. 22 patients were followed for 2 years. Medication off/stimulation on total UPDRS motor scores were improved by 29% when compared to the baseline medication off motor scores. The contralateral motor scores improved by 49%, whereas the axial motor scores by 18% in medication off/stimulation on condition. The duration and severity of levodopa induced dyskinesia were reduced respectively by 73% and by 77%. The daily levodopa dose was decreased by only 10%. Unilateral STN stimulation is a safe and effective procedure for selected patients with marked asymmetry Parkinson"s disease motor symptoms and early motor complications.

Application of proton magnetic resonance spectroscopy on substantia nigra metabolites in Parkinson’s disease

This study investigates changes in substantia nigra metabolites in Parkinson's disease (PD) using proton magnetic resonance spectroscopy ((1)H- MRS). Thirty patients with asymmetric PD and 20 normal controls were included in this study. Substantia nigra metabolites were detected in all subjects using 3D-multimer (1)H-MRS with a 3.0T MRI scanner. The relative ratios of NAA/Cr, NAA/Cho, NAA/(Cho + Cr) in the substantia nigra were compared between two sides of asymmetric PD patients as well as between PD patients and controls. Significant differences in NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were observed between PD patients and healthy controls (P < 0.05) as well as between the ipsilateral and contralateral of affected extremity in PD patients (P < 0.05). Significant differences in NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were also observed between patients with mild and severe PD. Thus, we found that (1)H-MRS can be used to detect substantia nigra metabolites in PD patients, which may be useful for early diagnosis and evaluation of PD.

A functional magnetic resonance imaging study of pathophysiological changes responsible for mirror movements in Parkinson's disease.

Mirror movements correspond to involuntary movements observed in the limb contralateral to the one performing voluntary movement. They can be observed in Parkinson’s disease (PD) but their pathophysiology remains unclear. The present study aims at identifying their neural correlates in PD using functional magnetic resonance imaging. Ten control subjects and 14-off drug patients with asymmetrical right-sided PD were included (8 with left-sided mirror movements during right-hand movements, and 6 without mirror movements). Between-group comparisons of BOLD signal were performed during right-hand movements and at rest (p<0.005 uncorrected). The comparison between PD patients with and without mirror movements showed that mirror movements were associated with an overactivation of the insula, precuneus/posterior cingulate cortex bilaterally and of the left inferior frontal cortex and with a deactivation of the right dorsolateral prefrontal cortex, medial prefrontal cortex, and pre-supplementary motor area and occipital cortex. These data suggest that mirror movements in Parkinson’s disease are promoted by: 1- a deactivation of the non-mirroring inhibitory network (dorsolateral prefrontal cortex, pre-supplementary motor area); 2- an overactivation of prokinetic areas (notably the insula). The concomitant overactivation of a proactive inhibitory network (including the posterior cingulate cortex and precuneus) could reflect a compensatory inhibition of mirror movements.

An ERP study of vocal emotion processing in asymmetric Parkinson's disease.

Parkinson's disease (PD) has been related to impaired processing of emotional speech intonation (emotional prosody). One distinctive feature of idiopathic PD is motor symptom asymmetry, with striatal dysfunction being strongest in the hemisphere contralateral to the most affected body side. It is still unclear whether this asymmetry may affect vocal emotion perception. Here, we tested 22 PD patients (10 with predominantly left-sided [LPD] and 12 with predominantly right-sided motor symptoms) and 22 healthy controls in an event-related potential study. Sentences conveying different emotional intonations were presented in lexical and pseudo-speech versions. Task varied between an explicit and an implicit instruction. Of specific interest was emotional salience detection from prosody, reflected in the P200 component. We predicted that patients with predominantly right-striatal dysfunction (LPD) would exhibit P200 alterations. Our results support this assumption. LPD patients showed enhanced P200 amplitudes, and specific deficits were observed for disgust prosody, explicit anger processing and implicit processing of happy prosody. Lexical speech was predominantly affected while the processing of pseudo-speech was largely intact. P200 amplitude in patients correlated significantly with left motor scores and asymmetry indices. The data suggest that emotional salience detection from prosody is affected by asymmetric neuronal degeneration in PD.

Five-year follow-up of 23 asymmetrical Parkinson's disease patients treated with unilateral subthalamic nucleus stimulation.

In this study, 23 asymmetrical Parkinson's disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified Parkinson's Disease Rating Scale II, III and axial symptom scores in the off-drug condition were significantly increased compared those at baseline. However, total Unified Parkinson's Disease Rating Scale II, III and axial symptom scores were significantly lower with stimulation-on compared with the synchronous stimulation-off state in off-drug condition, and the motor symptoms of contralateral side limbs were effectively controlled. Only low Hoehn-Yahr stage was correlated with good long-term postoperative improvement in motor symptoms. The mean levodopa-equivalent daily dose after stimulation treatment was significantly lower than that before treatment, but dyskinesias became worse. Our experimental findings indicate that unilateral deep brain stimulation of the subthalamic nucleus is an effective treatment for improving motor symptoms in well selected asymmetrical Parkinson's disease patients presenting no severe axial symptoms and dyskinesias.

Mirror movements in movement disorders: a review.

Mirror movements (MM) are involuntary movements of homologous muscles during voluntary movements of contralateral body regions. While subtle mirroring can be present in otherwise healthy adults, overt MM may be common in many movement disorders. Examining these collective findings may further our understanding of MM and help define their usefulness as a clinical sign. We sought to review English language research articles examining the presence, clinical significance, and/or pathophysiology of MM in Parkinson's disease (PD), corticobasal syndrome (CBS), essential tremor (ET), focal hand dystonia, Creutzfeldt-Jakob's disease (CJD), and Huntington's disease. When available, MM in these disorders were compared with those of healthy age-matched controls and congenital disorders such as Klippel-Feil syndrome and X-linked Kallman's syndrome. Clinical presentation of MM is common in asymmetric parkinsonian disorders (early PD, CBS) and manifests differently depending on the side affected (less affected hand in PD, more affected hand in CBS, either hand in ET, and both hands in healthy adults and congenital disorders), stage of disease (early, asymmetric PD and CJD), and presence of concomitant mirror-like overflow phenomena (focal dystonia and CBS-associated alien hand). In general, uncrossed descending corticospinal projections (congenital MM) and/or abnormal activation of the motor cortex ipsilateral to the voluntary task (most acquired MM), i.e., activation of the normal crossed corticospinal pathway, are required for the generation of MM. MM are common motor phenomena and present differently in several acquired (mostly neurodegenerative) and congenital movement disorders. Future studies on MM will enhance the clinical diagnosis of selected movement disorders and contribute to our understanding of the normal physiology of bimanual coordination.

Handedness correlates with the dominant Parkinson side: A systematic review and meta‐analysis

Parkinson's disease (PD) characteristically presents with asymmetrical symptoms, contralateral to the side of the most extensive cerebral affection. This intriguing asymmetry, even included in the definition for diagnosing PD, however, is still part of a mystery. The relation with handedness as a common indicator of cerebral asymmetry might provide a clue in the search for causal factors of asymmetrical symptom onset in PD. This possible relationship, however, is still under debate. The objective of this study was to establish whether a relation between handedness and dominant PD side exists. We searched for cross-sectional or cohort studies that registered handedness and onset side in PD patients in PubMed, EMBASE, and Web of Science from their first record until 14 February 2011. Data about handedness and dominant PD side was extracted. Authors who registered both but not described their relation were contacted for further information. Odds ratios (ORs) were analyzed with a fixed effect Mantel-Haenszel model. Heterogeneity and indications of publication bias were limited. Our electronic search identified 10 studies involving 4405 asymmetric PD patients. Of the right-handed patients, 2413 (59.5%) had right-dominant and 1644 (40.5%) had left-dominant PD symptoms. For the left-handed patients this relation was reversed, with 142 (40.8%) right-dominant and 206 (59.2%) left-dominant PD symptoms. Overall OR was 2.13 (95% confidence interval [CI], 1.71-2.66). Handedness and symptom dominance in PD are firmly related with each other in such a way that the PD symptoms emerge more often on the dominant hand-side. Possible causal factors are discussed.

Perceptual bias for affective and nonaffective information in asymmetric Parkinson's disease.

To relate lateralized impairments of visual perception in Parkinson's disease to asymmetries in the severity of motor symptoms. Ten patients with worse left-sided motor symptoms (LPD), 15 with worse right-sided (RPD), and 13 healthy age-matched controls (all right-handed) viewed mirror-imaged pairs of emotional chimeric faces, (left side smiling, right neutral, and vice versa), of greyscales (strips whose luminance varied smoothly from black on the left to white on the right, and vice versa) and of gender chimeric faces (left side male, right female, and vice versa). Participants signaled which stimulus appeared happier, brighter, or more feminine, respectively, so showing which side received more attention. For emotional chimeras, controls and LPD showed little bias, whereas RPD showed a strong bias to left hemispace (p = .018, r = .45). Across all patients, this bias was associated with severity of right-sided motor impairment (p = .018, r = .49). The bias was much weaker and insignificant for greyscales (p = .72, r = .14). For gender chimeras, RPD again showed a significantly greater left hemispace bias than did LPD (p = .037, r = .47), although neither patient group differed significantly from controls. Across all patients, this bias correlated with ratio of right-to-left symptom severity (p = .044, r = .48). The left hemispace bias in RPD is greater for facial than for luminance judgments, and is amplified for emotional judgments. Asymmetrical degeneration of the striatum, particularly involving the left side, appears to underlie this deficit in visual processing.

Motor laterality asymmetry and nonmotor symptoms in Parkinson's disease

In patients with Parkinson's disease (PD), asymmetric motor signs provide an interesting model to evaluate whether asymmetric nigrostriatal degeneration can affect neuropsychological function and other nonmotor symptoms (NMS). This study was designed to evaluate the predominant laterality of motor symptoms and its relationship with cognition and other NMS in idiopathic PD. Nationwide, longitudinal, and multicenter study (ELEP Registry) using outpatients with PD. Left PD (LPD) and right PD (RPD) was defined based on the motor signs on the SCOPA-motor scale. To include the clinical spectrum of asymmetric PD patients, we considered two groups of patients with mild-moderate and extreme asymmetry. Predominant LPD or RPD with mild-moderate versus extreme asymmetry were compared using the following scales: cognition, psychosis (Parkinson Psychosis Rating Scale), anxiety/depression, sleep (and autonomic dysfunction at baseline and 1 year later. Nonparametric tests were used for comparison. One hundred forty-nine PD patients (74 RPD and 75 LPD) with mild-moderate asymmetry and 90 (47 RPD and 43 LPD) with extreme asymmetry and a mean age of 64.5 (10.4) years were included. Extreme RPD had higher Parkinson Psychosis Rating Scale scores over time (P = 0.005) compared with LPD, but no significant differences were observed between LPD and RPD in terms of other NMS. These findings suggest that damage to left-hemisphere plays a disproportionately greater role in PD-related psychosis over time. In contrast, motor laterality does not consistently affect other NMS, suggesting that NMS are related to a more widespread brain disorder.

Elevated [18F]FDOPA utilization in the periaqueductal gray and medial nucleus accumbens of patients with early Parkinson's disease

PET studies with the DOPA decarboxylase substrate 6-[18F]fluoro-l-DOPA (FDOPA) reveal the storage of [18F]-fluorodopamine within synaptic vesicles, mainly of dopamine fibres. As such, FDOPA PET is a sensitive indicator of the integrity of the nigrostriatal dopamine innervation. Nonetheless, there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods. To investigate this phenomenon further, we used voxel-wise steady-state kinetic analysis to search for regions of elevated FDOPA utilization (K; ml g−1 min−1) and steady-state trapping (Vd; ml g−1) in a group of well-characterized patients with early, asymmetric PD, who were contrasted with an age-matched control group. Subtraction of the population mean parametric maps revealed foci of increased FDOPA utilization K (+25%) in the bilateral medial nucleus accumbens, whereas the expected declines in the trapping of FDOPA were seen in the caudate and putamen. This observation suggests hyperfunction of catecholamine fibres innervating specifically the limbic striatum, which could guide the design of future prospective FDOPA-PET studies of the impulse control disorders occurring in some PD patients under treatment with dopamine agonists. A focus of increased FDOPA influx and also Vd was detected in the periaqueductal grey, consistent with some earlier reports based on reference tissue analysis. Increased FDOPA trapping in the periaqueductal grey of PD patients seems consistent with recent reports of increased activity of serotonin neurons in a rat model of parkinsonism.

Two‐year follow‐up on the effect of unilateral subthalamic deep brain stimulation in highly asymmetric Parkinson's disease

Although bilateral subthalamic deep brain stimulation (STN DBS) provides greater relief from the symptoms of Parkinson's disease (PD) than unilateral STN DBS, it has been suggested that unilateral STN DBS may be a reasonable treatment option in selected patients, especially those with highly asymmetric PD. In previous studies on the effect of unilateral STN DBS, the asymmetry of PD symptoms was not prominent and the mean follow-up durations were only 3 to 12 months. In this study, we report our findings in a series of 8 patients with highly asymmetric PD who were treated with unilateral STN DBS and were followed for 24 months. Serial changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and subscores in the ipsilateral, contralateral, and axial body parts were analyzed. Unilateral STN DBS improved the UPDRS motor score and the contralateral subscore in the on-medication state for 5 nonfluctuating patients and in the off-medication state for 3 fluctuating patients. However, the ipsilateral subscore progressively worsened and reversed asymmetry became difficult to manage, which led to compromised medication and stimulator adjustment. At 24 months, all the patients were considering the second-side surgery. Our results suggest that bilateral STN DBS should be considered even in highly asymmetric PD.

The G2019S LRRK2 mutation in Brazilian patients with Parkinson's disease: Phenotype in monozygotic twins

Mutations in the Leucine-Rich Repeat Kinase 2 gene (LRRK2) are mainly responsible for idiopathic Parkinson's disease (PD) with either a dominant pattern of transmission or a sporadic occurrence due to the reduced penetrance. A majority of LRRK2 kindreds demonstrate an extremely variable age-at-onset in affected members of the same family. The G2019S is the most common LRRK2 mutation, which accounts for 1-5% PD patients in North America, and up to 40% of patients from an isolated Arab population. We assessed the frequency of the G2019S mutation in 83 Brazilian PD patients originally preselected for having an early age-at-onset (<50 years) and/or a positive family history. The mutation was detected in three probands (3.5%). Our clinical findings in these kindreds include the first description of the phenotype in identical twins discordant for handedness (a general phenomenon found in approximately 25% monozygotic twins). However, both twins developed right asymmetric PD. The clinical presentation of twins was strikingly similar including an identical PD onset at age 60. This observation may suggest that genetic factors predominantly determine age-at-onset.