The International Parkinson and Movement Disorder Society (MDS) brings together thousands of clinicians, researchers, trainees and industry supporters each year who are interested in current research and approaches to the diagnosis and treatment of movement disorders. The goal is to share ideas, stimulate interest among all those involved in movement disorder treatment and research, and advance related clinical and scientific disciplines.
As PET has become more available, there have been efforts to use it in the differential diagnosis of parkinsonism. Despite some success in clinical settings, they are not being considered and there is more consensus on using a combination of techniques to help in the differential diagnosis. The search and development of new biomarkers now utilizes the [18F]PR04.MZ PET CT, which uses the dopamine transporter (DAT) as a ligand and provides a higher affinity and selectivity profile for DAT than previously used tracers. We hope that this will allow us to indirectly determine the density of presynaptic dopaminergic neurons more accurately. In fact, this PET-CT is the only one that can show the dopaminergic loss in the SNpc in Parkinson’s disease. It has now been investigated whether [18F]PR04.MZ-PET-CT can be a useful tool in the differential diagnosis of Parkinson’s and atypical Parkinson’s (AP) syndromes, mainly MSA and PSP, in the first 5 years after symptom onset [1]. A retrospective analysis was performed of a cohort of 34 HC patients and 75 patients with parkinsonian syndromes with less than 5 years of symptoms in whom the treating physician, a movement disorder specialist, decided to request a [18F]PR04.MZ PET-CT, presumably in cases where the diagnosis was inconclusive. The clinical diagnosis and the specific binding ratios (SBRs) for the anterior putamen, posterior putamen, caudate nucleus and substantia nigra were analyzed. SBRs were calculated as described by Juri et al.
It was found that HC had higher SBRs in all regions, that PD had fewer SBRs than HC with a rostrocaudal gradient (less SBR in the posterior putamen). It is notable that PSP showed greater impairment in all regions, but particularly in the putamen. The results suggest that [18F]PR04.MZ PET CT can provide information in the differential diagnosis of Parkinson’s disease and PSP in the first five years after the onset of symptoms. Whether it can be helpful for the differential diagnosis of other AP cannot be deduced from the results.
Long-term results of DBS therapy
During the off-phase of Parkinson’s motor symptoms, local field potentials (LFPs) of the β-band are observed in the basal ganglia. The intensity of the β-band is reported to correlate with the severity of off symptoms. Adaptive deep brain stimulation (DBS) uses a sensing technique that measures LFP from electrodes implanted in the target nucleus and automatically controls the stimulation program. This study investigated the long-term outcome of STN-THS in the adaptive environment [2]. Sixteen patients who received STN-DBS with an adaptive DBS-compatible neurostimulator and DBS electrodes were included. Their devices were programmed with adaptive settings at the beginning of treatment. Adaptive settings were used from the start of treatment. The motor scores of the UPDRS-III and the stimulation programs were evaluated 1, 3, 6 and 12 months after the adaptive settings.
15 patients were selected for STN-DBS and one patient for GPi-DBS. In 26 of 32 electrodes, beta-band LFPs were detected in the resting state of motor symptoms, which disappeared in the active state. In all patients, beta-band LFPs were obtained from at least one hemisphere, and when beta-band LFPs were obtained from only one hemisphere, adaptive DBS was set based on the LFP from one hemisphere bilaterally. Current values were increased by 36.0% at one month after surgery, 113.3% at three months after surgery, 164.0% at six months after surgery, and 182.7% at 12 months postoperatively compared to values measured immediately after implantation, with no deterioration in motor scores. During the course of the study, the adaptive settings became invalid in six patients, in three of them due to a measurement error caused by artifacts and in three others due to several peaks in the beta band. In all cases, the adaptive setting could be adjusted by reconfiguration. In the postoperative acute phase, the current value was automatically adapted to the increased energy demand caused by the loss of the microlesion effects of implantation to maintain motor function. Adaptive deep brain stimulation is expected to improve and maintain motor function in Parkinson’s patients.
Parkinson’s and its subtypes
Parkinson’s disease (PD) can be divided into serotonergic, non-adrenergic and cholinergic based on non-motor symptoms. Studies have demonstrated the association between the 5HTTLPR (44bp Ins/Del) polymorphism and PD risk. However, the factors that determine the subtypes remain unknown. Therefore, the current study aimed to determine the association between the 5HTTLPR (44bp Ins/Del) polymorphism and PD neurotransmitter subtypes [3]. 150 PD patients were recruited based on the criteria of the Brain Bank of the UK Parkinson’s Society. The polymorphism was determined by PCR-RFLP method and its association with Parkinson’s disease neurotransmitter subtype was analyzed. Among the Parkinson’s patients, the serotonergic subtype was the most common (66.44%), followed by the cholinergic (16.78%) and noradrenergic (15.44%) subtypes. Dominant (L/L vs. L/S+S/S) (OR: 2.8, 95% CI: 1.3-5.9, p=0.009), recessive (L/L+L/S vs. S/S) (OR: 5.1, 95% CI: 1, 8-14.1, p=0.0007) and allele models (L Vs S – OR: 2.6, 95% CI: 1.5-4.3, p=0.0001) of 5HTTLPR (44Ins/Del) were associated with the risk of serotonergic symptoms. The results therefore indicate that the 5HTTLPR (44bp Ins/Del) gene polymorphism is associated with the risk of Parkinson’s disease and may also be a contributing factor for the serotonergic subtype of Parkinson’s disease.
Paroxysmal movement disorders in pediatrics
Paroxysmal movement disorders (PxMD) are characterized by episodic involuntary movements and are subdivided into paroxysmal dyskinesias (PD) and episodic ataxias (EA). Although they have been mentioned in the medical literature since 1892, much is still unknown about PxMD, including the exact prevalence. There is little literature on the results of genetic testing, the optimal testing approach and treatment outcomes in children. A cross-sectional cohort study including retrospective chart and patient reviews (clinical presentation, treatment outcome, genetics, neuroimaging, electrophysiology) has now been conducted [4]. 79 cases met the inclusion criteria (PD=37, EA=38, AHC=4). The point prevalence for all PxMD was 6.5 cases per 100 000 persons under 18 years of age (PD 3/100 000, EA 3.1/100 000, AHC 0.3/100 000). Sixty-six cases were clinically verified. A cause was identified in 34% (22/64), with no difference between the PD (42%, 14/33) and EA (26%, 8/31) subgroups. Single-gene testing (35%, 7/20) had the highest investigative yield, followed by gene panels (25%, 11/44), whole genome sequencing (25%, 2/8) and whole exome sequencing (9%, 1/11). Neuroimaging and EEG were performed in 73% (47/64) and 59% (47/64), respectively. In no case did this contribute to the diagnosis. A variable evolution was observed. For PD, 43% (14/33) resolved and 33% (11/33) improved, with 52% (17/33) attributable to medication. For EA, 45% (14/31) resolved and 42% (13/31) improved, with 48% (17/33) due to self-healing.
This study was the first to determine the prevalence of PxMD in a pediatric population. The prevalence (6.5 per 100,000<18 years) is higher than the estimates for the adult population. Nevertheless, PxMD are rare and diagnosis often takes a long time. The study showed that the aetiology is only identified in a third of patients. Fortunately, the majority of patients can expect to improve with medication or self-healing.
Understanding dystonia
Dystonia is a hyperkinetic movement disorder. Recently, there has been an increased interest in understanding the various non-motor symptoms. A detailed understanding of these non-motor symptoms will help in the development of appropriate therapeutic strategies. Sixty patients with idiopathic dystonia participated in a cross-sectional study at NIMHANS, Bengaluru [5]. Demographic data were noted and severity of motor symptoms was assessed using BFMDRS and UDRS. Various validated scales measured non-motor symptoms including RBDSQ, ESS, PSQI, HADS-A, HADS-D, MoCA, WHO-QoL. Caregiver stress was measured using the Zarit scale. The average age was 28.63 ± 11.96 years. Men (n=41) outnumbered women (n=19). The mean age at onset of illness was 21.01 ± 13.89 years. The mean duration of illness was 8.55 ± 7.45 years. Subjectively, the most common non-motor symptoms reported were pain, anxiety, sleep disturbances and depression. Generalized dystonia occurred predominantly in infancy and childhood, segmental/multifocal dystonia in adolescence and adulthood. In 30%, other movement disorders (chorea, parkinsonism, myoclonus, ataxia) occurred simultaneously. Levodopa was effective in 26.6% (16 patients). No RBD was observed in any of the patients, the mean RBDSQ score was 2.33±1.48. The ESS score was 3.00±2.11. The WHO QoL score was 78.44±10.21. The HADS-A score was 6.03±3.08 and the HADS-D score was 7.08±2.95. There was a positive correlation between the BFMDRS score and the Zarit score for caregiver burden, which was not significant. The study provides a detailed account of various non-motor symptoms of idiopathic dystonia. The severity of dystonia correlates positively with caregiver burden and emphasizes holistic care. Non-significant correlations with specific non-motor symptoms emphasize the multifaceted impact of the disorder. The results emphasize the need for comprehensive patient care and research into environmental genetic factors in the etiology of dystonia and non-motor symptoms.
Tremor under control
Deep brain stimulation (DBS) is an alternative treatment for disabling and refractory essential tremor (ET). Although deep brain stimulation of the ventral intermediate nucleus (VIM) has shown a positive effect, there is evidence that deep brain stimulation in the posterior subthalamic area (PSA) may be more effective. The differences in clinical, electrical and QoL outcomes between VIM-DBS and PSA-DBS need to be better characterized. A randomized, double-blind, crossover clinical trial was conducted in patients with disabling and refractory ET treated with DBS. Bilateral octopolar leads were implanted with a trajectory covering VIM (proximal contacts) and PSA (distal contacts). They were randomly assigned to Group 1 (PSA-VIM) or Group 2 (VIM-PSA) and received stimulation at each target for 3 months. The primary endpoint was measurement of improvement in ET using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) with total and arm item scores. Secondary endpoints were measurement of improvement in quality of life as measured by the visual analog scale (VAS-QoL), detection of potential adverse events (AEs), and assessment of energy requirements.
Eleven patients (6 women/5 men, mean age 63±7.6 years) were randomly assigned to group 1 (n=5) or group 2 (n=6). There was no evidence of a period or sequence effect. Both PSA-DBS and VIM-DBS significantly reduced tremor severity and improved quality of life. However, the improvement in FTM-TRS total and arm item scores was significantly better with PSA-DBS than with VIM-DBS, with a mean paired difference of -4.82 points (p=0.032) and -1.27 points (p=0.027), respectively. No statistically significant differences were found in stimulation amplitudes (mean difference -0.23 mA, p=0.386), VAS-QoL (mean difference 0.91 points, p=0.211) or AEs (neither frequency nor type, p=0.7124). There were no serious complications or sequelae associated with DBS. The study shows that both PSA-DBS and VIM-DBS are effective and safe in the treatment of essential tremor, but PSA-DBS produced a better response in terms of tremor suppression than VIM-DBS. In addition, there was a trend towards lower stimulation amplitudes required with PSA-DBS.
MSA with reduced MIBG
123I-MIBG myocardial scintigraphyis considered an effective tool to differentiate Parkinson’s dementia from Parkinson’s syndromes, including multisystem atrophy (MSA). However, previous studies have reported that reduced MIBG accumulation may occur in patients with MSA. Subjects included 35 patients with MSA (age 70.1 ± 7.4 years; mean ± SD), 90 patients with Parkinson’s disease (age 71.9 ± 7.8 years; mean ± SD) and 14 patients with essential tremor (ET). One patient (age 72.6 ± 7.5 years; mean ± standard deviation) underwent MIBG myocardial scintigraphy, and the H/M ratio and washout rate (WR) of the early and late images were compared. Subsequently, the 35 MSA patients were divided into two groups: 23 MSA-P patients and 12 MSA-C patients, and a similar study was performed [6]. There was a significant difference in the H/M ratio between early and late images between PD and MSA and between PD and ET, but there was no significant difference between MSA and ET. Decreased MIBG uptake was observed in 8 of 35 patients (22.8%) with MSA. Decreased MIBG uptake was observed in 76 of 90 patients (84.4%) with PD. There was no significant difference in the H/M ratio between the two groups, both in the early and late stages. Among the 35 MSA cases, H/M was below the threshold in 8 cases in early admissions, in 7 cases in MSA-P and in 1 case in MSA-C. Although MSA-P occurred more frequently, there was no significant difference. There was also no significant difference in disease duration between cases with reduced MSA uptake and those with reduced PD uptake.
In the MSA uptake group, uptake was reduced to the same level as in Parkinson’s disease. Furthermore, there was no difference in disease duration, suggesting that a mechanism other than transsynaptic degeneration may be responsible for the reduced uptake. In addition, it is hypothesized that there is a group of MSA patients who exhibit cardiac sympathetic dysfunction to the same extent as in Parkinson’s disease.
The risk of malnutrition
Malnutrition is one of the non-motor symptoms that is often overlooked but is closely related to PD progression, symptom fluctuations and cognitive dysfunction. However, there are no tools to predict the risk of malnutrition in PD patients and screening for malnutrition is often overlooked. In recent years, clinical prediction models have gained attention among healthcare professionals. One of the most widely used prediction models is the nomogram, which has been used to create prediction models for the risk of malnutrition in chronic heart failure, type 2 diabetes and other diseases. However, there is no report on predicting the risk of malnutrition in Parkinson’s disease. A cross-sectional study was conducted from February 2022 to December 2023 [8]. Parkinson’s patients from inpatient and outpatient departments were included in the study. The nutritional status of the patients was assessed using the Mini Nutritional Assessment (MNA). The nomogram was developed on the basis of risk factors determined by univariate and multivariate logistic regression analyses.
The study included 163 patients with a prevalence of malnutrition of 4.29%. In addition, 46.63% of patients were at risk of malnutrition. The main risk factors for malnutrition in this cohort were gender, BMI, GCSI score, Barthel score and MOCA score. The AUC of the nomogram model reached 0.923 (95% CI: 0.89-0.96), with an optimal cut-off value of 0.392. The model showed a sensitivity of 77.5% and a specificity of 88%. The bootstrap-based internal verification results yielded a C-index of 0.922, while the calibration curves indicated a strong correlation between the actual and predicted risks of malnutrition. The prevalence of malnutrition is high in patients with Parkinson’s disease. In the study, the nomogram model proved to be an effective tool for predicting malnutrition in patients with Parkinson’s disease.
Congress: International Parkinson and Movement Disorder Society
Literature:
- Montalva C, Sanchez M, Fuentes J, et al: [18F]PR04.MZ PET CT as a clinical tool in the differential diagnosis of PD and other atypical parkinsonian syndromes in the first 5 years of symptoms [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/18fpr04-mz-pet-ct-as-a-clinical-tool-in-the-differential-diagnosis-of-pd-and-other-atypical-parkinsonian-syndromes-in-the-first-5-years-of-symptoms. Accessed October 4, 2024.
- Kimura K, Kishida H, Kawasaki T, et al: 12-month long-term outcomes of adaptive DBS using LFP sensing technology [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/12-month-long-term-outcomes-of-adaptive-dbs-using-lfp-sensing-technology. Accessed October 4, 2024.
- Syed T, Kandadai R, Yaranagula S, et al: 5HTTLPR (44bp Ins/Del) polymorphism: Serotonergic subtype of Parkinson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/5httlpr-44bp-ins-del-polymorphism-serotonergic-subtype-of-parkinsons-disease. Accessed October 4, 2024.
- Harvey S, Allen N, Byrne S, et al: A better understanding of Paediatric Paroxysmal Movement Disorders [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/a-better-understanding-of-paediatric-paroxysmal-movement-disorders. Accessed October 4, 2024.
- Gowda N, Kamble N, Holla VV, et al: Pal. A Comprehensive Evaluation of the Non-Motor Symptoms, Quality of Life and Caregiver Burden in Patients with Idiopathic Dystonia [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/a-comprehensive-evaluation-of-the-non-motor-symptoms-quality-of-life-and-caregiver-burden-in-patients-with-idiopathic-dystonia. Accessed October 4, 2024.
- Triguero-Cueva L, Madrid Navarro CJ, Perez Navarro MJ, et al: A Double-blind, Randomized, Crossover Clinical Trial comparing VIM vs. PSA Deep Brain Stimulation for Disabling Essential Tremor [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/a-double-blind-randomized-crossover-clinical-trial-comparing-vim-vs-psa-deep-brain-stimulation-for-disabling-essential-tremor. Accessed October 4, 2024.
- Yokoyama R, Yamamoto T: A group of patients with multiple system atrophy (MSA) exhibit cardiac sympathetic dysfunction to the same extent as Parkinson’s disease (PD). [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/a-group-of-patients-with-multiple-system-atrophy-msa-exhibit-cardiac-sympathetic-dysfunction-to-the-same-extent-as-parkinsons-disease-pd. Accessed October 4, 2024.
- Huang Q, Zou X: A Nomogram Model for Predicting Malnutrition among Patients with Parkinson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). www.mdsabstracts.org/abstract/a-nomogram-model-for-predicting-malnutrition-among-patients-with-parkinsons-disease. Accessed October 4, 2024.
InFo NEUROLOGIE & PSYCHIATRIE 2024; 22(5): 24–26 (published on 21.10.24, ahead of print)
