Cervical Vestibular-Evoked Myogenic Potentials (cVEMPs) in Parkinson's Disease Patients: Prospective, Case-Control study

EP 140. Vestibular evoked myogenic potentials: A retrospective analysis

Patients with autonomic neuropathy associated with Parkinson's disease often show reverse dipping pattern/nocturnal hypertension at 24-h ambulatory blood pressure (BP) monitoring (24-h ABPM) and diurnal orthostatic hypotension. The aim of the study was to evaluate cardiac alterations in Parkinson's disease patients with reverse dipping, in comparison with non-reverse dippers Parkinson's disease and essential hypertensive patients. A total of 26 consecutive Parkinson's disease patients with reverse dipping at 24-h ABPM and no previous history of hypertension were compared with 26 non-reverse Parkinson's disease patients matched for age, sex and 24-h mean BP, and 26 essential hypertensive patients matched for nighttime mean BP. None of the Parkinson's disease patients suffered from cardiovascular diseases or were treated with antihypertensive or antihypotensive drugs. Reverse dipping was defined by a systolic day-night BP difference less than 0% at 24-h ABPM. Left ventricular (LV) hypertrophy was defined by a LV mass index at least 115 g/m in men and at least 95 g/m in women. LV mass, indexed for BSA, was significantly higher in reverse dipping than non-reverse Parkinson's disease patients (respectively 90.2 ± 25.3 vs. 77.4 ± 13.3 g/m, P = 0.04), and was similar to essential hypertensive patients (91.6 ± 24.8, P = 0.92). LV hypertrophy was detected in five reverse dipping Parkinson's disease patients and four hypertensive patients, but was not present in non-reverse Parkinson's disease patients (P = 0.046). Nocturnal BP values, nocturnal BP load, weighted BP variability and age were found to correlate with the increased LV mass index. Reverse dipping and nocturnal hypertension are related to higher LV mass and increased prevalence of LV hypertrophy in Parkinson's disease patients.

Excessive daytime sleepiness is common in Parkinson's disease and has been associated with Parkinson's disease-related dementia. Narcoleptic features have been observed in Parkinson's disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinson's disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinson's disease have been inconclusive. Reports of sleep studies in Parkinson's disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinson's disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinson's disease patients without dementia and 20 Parkinson's disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinson's disease patients without dementia and seven Parkinson's disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinson's disease patients without dementia and Parkinson's disease patients with dementia than controls (P < 0.01) and scores >10 were more frequent in Parkinson's disease patients with dementia than in Parkinson's disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 +/- 47.15 pg/ml; without dementia = 300.99 +/- 58.68 pg/ml; with dementia = 309.94 +/- 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinson's disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinson's disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.

Objective To investigate the characteristics of prospective memory impairment and event related potentials(ERPs)changes in Parkinson's disease(PD)patients without early treatment.Methods Event-based prospective memory(EBPM),time-based prospective memory(TBPM)and ERPs were examined in 33 PD patients and 31 healthy controls matched with age,gender,education and occupation.Results The scores of EBPM and TBPM in PD patients were significantly lower than those in normal controls(P＜0.05).The latencies of N2 and P300 were significantly prolonged,and P300amplitude was markedly decreased in PD patients as compared with those in normal controls(P＜0.05).The relative analysis showed that the P300 latency was positively correlated with both EBPM(r=0.628,P=0.000)and TBPM(r=0.582,P=0.000).Conclusion The EBPM and TBPM impairment might exist in PD patients without early treatment; the P300 latency can be used as a predictive electrophysiological marker to assess the severity of EBPM and TBPM impairment in PD patients. Key words: Parkinson disease; Memory disorder; Neuropsychological test; Cognition

Visual processing speed in freezing and non-freezing Parkinson’s disease patients

BackgroundPostural instability is a common problem in patients with Parkinson’s disease (PD). The appropriate cooperation of vestibular, visual, and proprioceptive signals along with apt anticipatory and adaptive postural responses is essential for postural stability. Abnormalities in this sensorimotor admixture lead to postural instability in PD. The function of vestibular otolith function and its central connections in postural instability of PD is still obscure. Cervical vestibular-evoked myogenic potentials (VEMP) can be used to assess the function of the saccular part of otolith and its connections.PurposeWe aimed to study the role of dysfunction of the saccule and its connections at the brainstem by comparing the VEMP with normal controls and correlating it with the postural instability in patients with PD.MethodsThirty patients with PD and 30 healthy volunteers were included in the study, after obtaining the institutional ethical committee approval. Patient’s demographic data, stage and duration of illness, treatment history, history of fall, postural instability, Unified Parkinson’s Disease Rating Scale (UPDRS) score, and Non-Motor Symptoms Scales (NMSs) were noted. Cervical VEMP analysis was done for both patients and controls.Results and ConclusionPatients with absent VEMP had significant postural instability, a history of falls, and a high UPDRS score. Mean P13 and N23 latencies were prolonged, and the amplitude was significantly low in patients with PD. Absent cVEMP was significantly associated with postural instability, non-motor symptoms, especially gastrointestinal, miscellaneous symptoms, and mood/cognition. VEMP can be considered an early electrophysiological marker for dysfunction of otolith and its central connections.

Adapting to post-COVID19 research in Parkinson's disease: Lessons from a multinational experience

Resting-state fMRI in Parkinson's disease patients with cognitive impairment: A meta-analysis

The performance on a visual Go/NoGo (VGNG) task during walking has been used to evaluate the effect of gait on response inhibition in young and older adults; however, no work has yet included Parkinson's disease (PD) patients for whom such changes may be even more enhanced. In this study, we aimed to explore the effect of gait on automatic and cognitive inhibitory control phases in PD patients and the associated changes in neural activity and compared them with young and older adults. 30 PD patients, 30 older adults, and 11 young adults performed a visual Go/NoGo task in a sitting position and during walking on a treadmill while their EEG activity and gait were recorded. Brain electrical activity was evaluated by the amplitude, latency, and scalp distribution of N2 and P300 event related potentials. Mix model analysis was used to examine group and condition effects on task performance and brain activity. The VGNG accuracy rates in PD patients during walking were lower than in young and older adults (F = 5.619, p = 0.006). For all groups, N2 latency during walking was significantly longer than during sitting (p = 0.013). In addition, P300 latency was significantly longer in PD patients (p < 0.001) and older adults (p = 0.032) during walking compared to sitting and during 'NoGo' trials compared with 'Go' trials. Moreover, the young adults showed the smallest number of electrodes for which a significant differential activation between sit to walk was observed, while PD patients showed the largest with N2 being more strongly manifested in bilateral parietal electrodes during walking and in frontocentral electrodes while seated. The results show that response inhibition during walking is impaired in older subjects and PD patients and that increased cognitive load during dual-task walking relates to significant change in scalp electrical activity, mainly in parietal and frontocentral channels.

The association of Parkinson's disease and cancer had recently attracted renewed interest, and results are coming from well-designed epidemiologic studies (mainly cohort studies). In particular, the findings from Danish Parkinson's disease patients (1, 2) showed that the association between Parkinson's disease and melanoma was present both before and after the diagnosis of Parkinson's disease and was not explained by levodopa treatment. The suspicion that levodopa could increase the risk of melanoma was suggested in several clinical reports, the first of which appeared soon after the drug was introduced as a new therapy for Parkinson's disease in the early 1970s. The hypothesis seemed biologically plausible, but the evidence did not support a causal relationship (3-6). On the contrary, the increased risk of melanoma in Parkinson's disease patients is now well established, although a clear biological explanation is still lacking. For other cancers, the cohort study of the Danish Parkinson's disease patients confirmed an inverse association with smoking-related cancers (standardized incidence ratio: 0.38 for lung cancer and 0.47 for larynx cancer). This inverse association was first seen in 1966 by Hammond (7) and in 1976 by Doll and Peto (8).The study of Driver et al. (9) published in this issue of Cancer Epidemiology Biomarkers &amp; Prevention has the merit of reinforcing the evidence of an association between Parkinson's disease and melanoma in a prospective study with good control of confounding (and modifying) factors. A possible confounder of the association between melanoma and Parkinson's disease is social class, as melanoma and Parkinson's disease seem to be more frequent in higher socioeconomic status individuals with more opportunities for recreational (and thus intermittent) sun exposure. In contrast, this study clearly showed that socioeconomic factors could not be indicted as responsible for the association. Indeed, the “matching” for social class was elegantly done, recruiting both Parkinson's disease cases and controls from the Physician's Health Study cohort; the excess risk for melanoma remained.Nonetheless, the findings of this study raise a even more intriguing question. First, this study confirmed the decreased risk of cancers other than melanoma and, in particular, of smoking-related cancers, previously observed not only in Parkinson's disease patients (1, 2, 10) but also in those with other neurological diseases (11). Future studies should concentrate on an appropriately powered search for possible genetic factors that predispose to Parkinson's disease, but decrease cancer risk, perhaps via an increased tendency to apoptosis. This approach will be facilitated by the nature of Parkinson's disease, a disease with good survival, high incidence in western countries, and frequently affecting patients of upper socioeconomic status with a good compliance to follow-up, thus allowing cohort and nested case-control designs to provide sufficient power. However, second and more surprisingly, this study also showed that smokers among Parkinson's disease patients had fewer tobacco-related cancers than smokers in the reference group.Thus, there is an intriguing picture of fewer smokers among Parkinson's disease patients and even fewer tobacco-related cancers among Parkinson's disease patients who smoked. Although the first inverse association was already known, this second finding is completely new and suggests a gene-environment interaction. The authors hypothesized a role for CYP2D6 with a less efficient polymorphism among the Parkinson's disease patients, leading to poor toxin metabolism and to a decreased activation of pro-carcinogens present in tobacco smoke. Other factors could be involved, including other P450 enzymes or genes involved in the DNA excision-repair pathway. Certainly, further studies will help us to understand the biologic mechanisms.It is, therefore, time for a gene-environment study of melanoma and other cancers, measuring candidate genes (or a genome-wide scan) in the setting of a study with validated histories of sun exposure and tobacco smoking. Meanwhile, the study by Driver et al. itself, as further person-years accumulate, should be able to better estimate the risk of each type of cancer among Parkinson's disease patients.

Objective To investigate the apathy and neuropsychological characteristics of newly diagnosed Parkinson's disease (PD) patients. Methods Eighty-two newly diagnosed PD patients and 30 matched healthy controls by age, sex and education level were recruited in the present study.Apathy was assessed using Apathy Evaluation Scale (AES) and related factors, including age, sex, education level and disease duration were simultaneously evaluated.Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD), as well as Montreal Cognitive Assessment (MoCA) were employed in order to respectively evaluate the motor function, depression and cognition. Results The AES scores in the PD patients were significantly higher when compared to the healthy controls. The prevalence of apathy and depression in the PD patients was 51.2%(42/82) and 19.5%(16/82), respectively. There were no statistically significant differences in age, sex, education level, UPDRS-Ⅱ/Ⅲ scores and MoCA scores between apathy (n=42) and no-apathy (n=40) PD patients (P>0.05), while the statistically significant difference in HAMD scores between apathy (n=42) and no-apathy (n=40)PD patients was shown (the HAMD scores of apathy PD patients were 10.61±3.30, the HAMD scores of no-apathy PD patients were 5.96±1.90, t=7.87, P<0.05). The correlation analysis indicated that there were no correlations between AES scores and the related factors, including age, education level, disease duration and UPDRS-Ⅱ/Ⅲ scores, but AES scores were positively correlated with HAMD scores. Conclusion In newly diagnosed PD patients, the apathy is independent of depression, motor dysfunction, as well as cognitive impairment, which may be an early signal for PD. Key words: Parkinson disease; Apathy; Neuropsychological test; Newly diagnosed

Background: Early brainstem neurodegeneration is common in Parkinson's disease (PD) and progressive supranuclear palsy (PSP). While previous work showed abnormalities in vestibular evoked myogenic potentials (VEMPs) in patients with either disorder as compared to healthy humans, it remains unclear whether ocular and cervical VEMPs differ between PD and PSP patients.Methods: We prospectively included 12 PD and 11 PSP patients, performed ocular and cervical VEMPs, and calculated specific VEMP scores (0 = normal, 12 = most pathological) based on latencies, amplitude, and absent responses. In addition, we assessed disease duration, presence of imbalance, motor asymmetry, and motor disability using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III). Moreover, we ascertained various sleep parameters by video-polysomnography.Results: PSP and PD patients had similar oVEMP scores (6 [3–6] vs. 3 [1.3–6], p = 0.06), but PSP patients had higher cVEMP scores (3 [0–6] vs. 0 [0–2.8], p = 0.03) and total VEMP scores (9 [5–12] vs. 4 [2–7.5], p = 0.01). Moreover, total VEMP scores >10 were only observed in PSP patients (45%, p = 0.01). MDS-UPDRS III correlated with cVEMP scores (rho = 0.77, p = 0.01) in PSP, but not in PD. In PD, but not in PSP, polysomnographic markers of disturbed sleep, including decreased rapid eye movement sleep, showed significant correlations with VEMP scores.Conclusions: Our findings suggest that central vestibular pathways are more severely damaged in PSP than in PD, as indicated by higher cervical and total VEMP scores in PSP than PD in a between-groups analysis. Meaningful correlations between VEMPs and motor and non-motor symptoms further encourage its use in neurodegenerative Parkinsonian syndromes.

The vestibular evoked myogenic potential (VEMP) is a technique used to assess vestibular function. Cervical VEMPs (cVEMPs) are obtained conventionally from the sternocleidomastoid (SCM) muscle; however, the dorsal neck muscle splenius capitis (SPL) has also been shown to be a reliable target alongside the SCM in young subjects. This study aimed to compare cVEMPs from the SCM and SPL in two positions across young, older, and Parkinson's disease (PD) patients. Experiments were carried out using surface EMG electrodes placed over the SCM and SPL. cVEMPs were measured using a 30s, 126dB sound stimulus with 222 individual tone bursts, while subjects were in a supine and head-turned posture (also known as the head elevation method), and in a seated head-turned posture. When comparing cVEMPs across positions, the incidence of supine and seated SCM-cVEMPs diminished significantly in older and PD patients in comparison with young subjects. However, no statistically significant differences in incidences were found in seated SPL-cVEMPs when comparing young, older and PD patients. SPL-cVEMPs were present significantly more often than seated SCM-cVEMPs in PD patients. SPL-cVEMPs are not altered to the same extent that SCM-cVEMPs are by aging and disease and its addition to cVEMP testing may reduce false-positive tests for vestibulopathy.

To analyze the clinical characteristics, correlation factors and clinical heterogeneities in Parkinson's disease (PD) patients with cognitive impairment and identify whether cognitive impairment could influence the aspect of sleep. A total of 130 PD outpatients and inpatients of sleep center at our hospital were eligible for participation. According to Montreal cognitive assessment (MOCA), they were divided into cognitive normal group (MOCA ≥ 26) (n = 51) and cognitive impairment group (MOCA < 26) (n = 79). Their clinical characteristics were mainly evaluated by unified Parkinson's disease rating scale (UPDRS) , Hoehn-Yahr (H-Y) stage, Hamilton depression scale (HAMD-24 item) and Epworth sleepiness scale (ESS). And all of them underwent video-polysomnography (PSG). The proportion of cognitive impairment (MOCA < 26) was 60.76%. Compared to those without cognitive impairment, the PD patients with cognitive impairment had significantly higher score of HAMD (10 ± 7 vs 7 ± 4), increased incidence of hallucinations (40.50% vs 19.60%) and REM behavior disorders (RBD) (63.29% vs 39.21%), significantly higher H-Y stage [2.5(2.0-3.0) vs 2.0 (2.0-2.5)] , United Kingdom Parkinson Disease Society (UPDRS) part III (22 ± 10 vs 19 ± 10) and levodopa-equivalent daily dose (LED) (511 ± 302vs 380 ± 272) (all P < 0.05). However, no significant differences existed in the subscores of MOCA between PD patients with different sides of onset and motor subtypes of onset (all P > 0.05). Non-conditional Logistic regression analysis showed that PD duration, score of HAMD and H-Y stage were the major influencing factors of cognition. On PSG, significantly decreased sleep efficiency (57% ± 21% vs 66% ± 17%), higher percentage of non-REM sleep stage 1 (NREMS1) (37% ± 21% vs 27% ± 13%), lower percentage of NREMS2 (40% ± 17% vs 46% ± 13%) and REM sleep (39% ± 28% vs 54% ± 36%) were found for PD patients with cognitive impairment (all P < 0.05). The PD patients with cognitive impairment have more severe disease and partial nonmotor symptoms. And the severity of disease and depression is closely associated with cognitive impairment. Cognitive impairment may also affect sleep to cause decreased sleep efficiency and severe sleep structure disorder.

Parkinson's disease (PD) is a neurodegenerative pathology characterized by the degeneration of midbrain dopamine neurons, whose development and maintenance in brain is related to the transcription factor NR4A2 (also called Nurr1). Notably, NR4A2 is a neuroprotective agent with anti-inflammatory role in microglia and astrocytes. Furthermore, mutations in NR4A2 gene are associated to the familial form of PD, and its gene expression level is down-regulated in blood obtained from PD patients. NR4A2 belongs to the NR4A subfamily consisting of three members: NR4A1, NR4A2, and NR4A3. The NR4A subfamily shares high degree of homology in their molecular structure and cooperates in a spectrum of functions ranging from central nervous system to immune control during physiological and pathological conditions. Considering the close functional link between the member of NR4A subfamily, we performed a gene expression analysis of NR4A1, NR4A2, and NR4A3 in peripheral blood obtained from PD patients and healthy controls (HC). Then, in order to evaluate possible involvement of the NR4A subfamily in other neurodegenerative processes, we carried out the same analysis on blood obtained from Alzheimer's disease (AD) patients. A correlation between clinical features and gene expression was also evaluated. We found a marked down-regulated gene expression of the NR4A subfamily obtained from PD patients, but only a NR4A1 decrease in AD patients compared to HC. This study reports that the entire NR4A subfamily and not only NR4A2 could be systemically involved in PD suggesting that the study of these factors could be a promising approach to develop PD therapy.