Evidence of heat sensitivity in people with Parkinson's disease.

Examining how heat affects people with Parkinson's disease is essential for informing clinical decision-making, safety, well-being, and healthcare planning. While there is evidence that the neuropathology associated with Parkinson's disease affects thermoregulatory mechanisms, little attention has been given to the association of heat sensitivity to worsening symptoms and restricted daily activities in people with this progressive disease. Using a cross-sectional study design, we examined the experiences of people diagnosed with Parkinson's disease in the heat. Two-hundred and forty-seven people completed an online survey (age: 66.0 ± 9.2 years; sex: male = 102 (41.3%), female = 145 (58.7%)), of which 195 (78.9%) reported becoming more sensitive to heat with Parkinson's disease. Motor and nonmotor symptoms worsened with heat in 182 (73.7%) and 203 (82.2%) respondents, respectively. The most commonly reported symptoms to worsen included walking difficulties, balance impairment, stiffness, tremor, fatigue, sleep disturbances, excess sweating, difficulty concentrating, and light-headedness when standing. Concerningly, over half indicated an inability to work effectively in the heat, and nearly half reported that heat impacted their ability to perform household tasks and social activities. Overall, heat sensitivity was common in people with Parkinson's disease and had a significant impact on symptomology, day-to-day activities and quality of life.

A Critical Appraisal of the Whack-a-Mole and Swivel Chair Signs in the Diagnosis of Functional Movement Disorders.

BACKGROUND: The demonstration of positive signs during neurological examination is a cornerstone of the diagnosis of functional movement disorders, however, the available data supporting the diagnostic value of some of these signs is limited. OBJECTIVES: To determine the diagnostic value (sensitivity and specificity) of the "whack-a-mole" (WAM) and "swivel chair" (SC) tests in patients with functional movement disorders (FMD). METHODS: We enrolled patients with functional and organic movements in the WAM test if they exhibited tremor, dystonia, myoclonus, chorea, or tics. For the SC test, patients with a gait disorder as their primary impairment were recruited. Two blinded movement disorder specialists rated the presence of these signs in edited videos. RESULTS: Inclusion criteria were met by 42 patients with FMD and 65 patients with organic movement disorders. Both tests demonstrated high specificity (means, 78% and 96%), but their sensitivity was low (means, 52% and 37%). Interobserver agreement for the WAM sign was 0.77 in the FMD group, against 0.28 in patients with organic movement disorders, whereas Movement Disorders Clinical Practice for Review Only for the SC sign was 0.69 in both groups. CONCLUSIONS: The present study indicates that physicians must be cautious in the application and interpretation of these clinical signs in the diagnosis of functional movement disorders, and they should be carefully considered and used as necessary.

Levetiracetam for the treatment of mild cognitive impairment in Parkinson's disease: a double-blind controlled proof-of-concept trial protocol.

BACKGROUND: Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson's disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer's disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance. METHODS: Twenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity. RESULTS: Episodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes. CONCLUSIONS: This study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643327 . Registered on 25 November 2020.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

How Is Functional Neurological Disorder Managed in Australian Hospitals? A Multi-Site Study Conducted on Acute Inpatient and Inpatient Rehabilitation Wards.

Background: Successful management for functional neurological disorder (FND) requires multidisciplinary involvement starting with providing a definitive diagnosis. Objectives: To observe clinical management of patients with FND during hospital admission. Methods: A prospective observational study was conducted over six Australian hospitals over a 4-month period. Data collected included patient demographics, communication of the diagnosis of FND, access to the multidisciplinary team, hospital length of stay (LOS), and emergency department (ED) presentations. Results: A total of 113 patients were included. Median LOS was 6 (interquartile range, 3-14) days. Thirty-five (31%) presented to ED with 9 (8%) re-presenting two or more times after hospital discharge. Total hospital utilization cost was AUD$3.5million. A new diagnosis was made in 82 (73%) patients. Inpatient referrals were made to neurology (81, 72%), psychology (29, 26%), psychiatry (27, 24%), and physiotherapy (100, 88%). Forty-four (54%) were not told of the diagnosis. Twenty (24%) did not have their diagnosis documented in their medical record. Of the 19 (23%) not reviewed by neurology on non-neurosciences wards, 17 (89%) did not have their diagnosis communicated and 11 (58%) did not have it documented. Twenty-five (42%) referred to neurology were not provided with a diagnosis. Conclusions: Current gaps in service provision during inpatient hospital admissions in Australia include low rates of communication of a diagnosis, particularly when patients are not located on a neurosciences ward, and limited and variable access to inpatient multidisciplinary teams. Specialized services are needed to improve education, clinical pathways, communication, and health outcomes while reducing healthcare system costs.

Health Care Utilization in Functional Neurologic Disorders: Impact of Explaining the Diagnosis of Functional Seizures on Health Care Costs.

Background and Objective: The objectives of this study were to investigate health care utilization costs of patients with video-electroencephalography (VEEG)-confirmed functional seizures (FS), determine whether patients who received a satisfactory functional neurologic disorder (FND) diagnosis explanation had reduced health care utilization compared with those with a poor explanation; and to quantify the overall health care costs 2 years prediagnosis and postdiagnosis for those receiving a different explanation. Methods: Patients with VEEG-confirmed pure FS (pFS) or mixed (functional seizure plus epileptic seizures) diagnosis between July 1, 2017, and July 1, 2019, were evaluated. Explanation of the diagnosis was determined "unsatisfactory" or "satisfactory" using self-developed criteria, and health care utilization data were collected using an itemized list. The subsequent costs 2 years post-FND diagnosis were compared with those 2 years before, and cost outcomes were compared between both groups. Results: In patients who received a satisfactory explanation (n = 18), total health care costs were reduced from $169,803 to $117,133 USD (-31%). An increase in costs was found ($73,430 to $186,553 USD = +154%) in patients with pPNES after an unsatisfactory explanation (n = 7). On an individual level, 78% with a satisfactory explanation saw a reduction in total health care costs per year (mean $5,111 USD to $1,728 USD), and in 57%, an unsatisfactory explanation led to an increase (mean $4,425 to $20,524 USD). A similar effect was seen from explanation on patients with a dual diagnosis. Discussion: The method of communicating an FND diagnosis has a significant impact on subsequent health care utilization. Those receiving satisfactory explanations demonstrated reduced health care utilization, whereas an unsatisfactory explanation resulted in additional expenses.

The antecedents and consequences of stereotype threat in Parkinson's disease.

OBJECTIVE: The aim of this study was to examine what factors make people with Parkinson's disease more susceptible to stereotype threat (i.e., the concern of being evaluated in line with negative group-based stereotypes) and the clinical consequences of this. METHOD: Forty-nine people with Parkinson's disease completed a measure of stereotype threat, as well as measures that indexed potential antecedents and clinical consequences of stereotype threat. RESULTS: Younger age and greater communication difficulties emerged as significant predictors of stereotype threat. Higher stereotype threat was also associated with increased emotional distress. CONCLUSIONS: These findings are an important first step in understanding stereotype threat in Parkinson's disease and may help to guide the development of intervention and educational efforts aimed at countering its effects.

Parkinson's disease disrupts the ability to initiate and apply episodic foresight.

OBJECTIVE: While Parkinson's disease is associated with impairments in many aspects of prospective cognition, no study to date has tested whether these difficulties extend to problems using episodic foresight to guide future-directed behavior. To provide the first examination of whether people with Parkinson's disease are impaired in their capacity to initiate and apply episodic foresight. METHOD: People with Parkinson's disease (n = 42), and a demographically matched neurotypical comparison group (n = 42) completed a validated behavioral assessment that met strict criteria for assessing episodic foresight (Virtual Week-Foresight), as well as a broader neurocognitive and clinical test battery. RESULTS: People with Parkinson's disease were significantly less likely than the comparison group to acquire items that would later allow a problem to be solved and were also less likely to subsequently use these items for problem resolution. These deficits were largely unrelated to performance on other cognitive measures or clinical characteristics of the disorder. CONCLUSIONS: The ability to engage in episodic foresight in an adaptive way is compromised in Parkinson's disease. This appears to be a stable feature of the disorder, and one that is distinct from other clinical symptoms and neurocognitive deficits. It is now critical to establish exactly why these difficulties exist and how they impact on real-life functional capacity.

Affective forecasting in Parkinson's disease.

OBJECTIVES: While emotional responses experienced in-the-moment appear to remain intact in Parkinson's disease (PD), no study has tested whether this extends to the prediction of future emotional responses. The present study aimed to provide the first assessment of affective forecasting capacity in this cohort. METHODS: A positively and negatively valenced affective forecasting task and broader clinical battery were completed by a PD group (ns = 28 and 37, respectively) and a demographically matched neurotypical control group (ns = 38 and 39, respectively). RESULTS: No group differences emerged on the two tasks, with the two groups underestimating their level of happiness and overestimating their level of negative affect to a similar degree. Affective forecasting error scores were unrelated to clinical characteristics. CONCLUSIONS: Given that affective forecasting relies on self-projection into the future, a skill shown to often be disrupted in this cohort, impairments were expected. However, this study provides initial evidence that this may not be the case. These findings are potentially important given that how we think about and envisage the future affectively is a major determinant of goal-directed behavior. Further work is now needed to establish whether these findings are robust and generalize to other types of affective stimuli.

Hazard Perception Skill and Driver Behavior in Patients With Functional Neurologic Disorders.

BACKGROUND AND OBJECTIVES: Driving in patients with functional neurologic disorders (FND) is a major concern, but current guidelines (where they exist) are based on expert consensus only due to a lack of relevant empirical evidence. This study aimed to provide such evidence by comparing drivers with FND with healthy controls on aspects of driving performance and behavior important to crash risk, including hazard perception skill. METHODS: Participants completed validated self-report questionnaires of driving behaviors (assessing lapses, errors, violations, and attentional issues) and 2 computer-based measures of hazard perception skill (both known to be associated with crash risk). RESULTS: We compared 43 patients who experience dissociative attacks or functional motor symptoms and 43 healthy controls. Patients with FND self-reported significantly more driving lapses and driving errors compared with healthy controls. However, there were no significant between-group differences in self-reports of ordinary violations, aggressive violations, or attention-related errors. Participants in the FND group and healthy controls exhibited a similar performance on a response time hazard perception test (6.27 vs 5.51 seconds, p = 0.245). However, participants with FND remarkably outperformed the controls in the number of plausible predictions they made in a verbal response hazard prediction test (1.55 vs 1.18 predictions per clip, p = 0.006). DISCUSSION: Our findings suggest that the ability of drivers with FND to predict traffic hazards in between attacks or flares is not worse than that of healthy individuals, with the possibility that it might even be better under some circumstances. Further studies with various populations are needed to replicate our findings.

'Tricked' sensory trick: a geste antagoniste in functional dystonia.

A sensory trick, or geste antagoniste, is a manoeuvre used by patients with dystonia to ameliorate their dystonic movements or posturing. Typically, a sensory trick is a confirmatory clue indicating an organic nature of the dystonia. In this report, we present an extremely rare case of a sensory trick in a patient with functional dystonia.

Moving beyond basic emotions in Parkinson's disease.

OBJECTIVE: Emotion recognition is a fundamental neurocognitive capacity that is a critical predictor of interpersonal function and, in turn, mental health. Although people with Parkinson's disease (PD) often exhibit difficulties recognizing emotions, almost all studies to date have focused on basic emotions (happiness, sadness, anger, surprise, fear, and disgust), with little consideration of how more cognitively complex self-conscious emotions such as contempt, embarrassment, and pride might also be affected. Further, the few studies that have considered self-conscious emotions have relied on high intensity, static stimuli. The aim of the present study was to therefore provide the first examination of how self-conscious emotion recognition is affected by PD using a dynamic, dual-intensity measure that more closely captures how emotion recognition judgements are made in daily life. METHOD: People with PD (n = 42) and neurotypical controls (n = 42) completed a validated measure of self-conscious facial emotion recognition. For comparative purposes, in addition to a broader clinical test battery, both groups also completed a traditional static emotion recognition measure and a measure of self-conscious emotional experience. RESULTS: Relative to controls, the PD group did not differ in their capacity to recognize basic emotions but were impaired in their recognition of self-conscious emotions. These difficulties were associated with elevated negative affect and poorer subjective well-being. CONCLUSIONS: Difficulties recognizing self-conscious emotions may be more problematic for people with PD than difficulties recognizing basic ones, with implications for interventions focused on helping people with this disorder develop and maintain strong social networks. PRACTITIONER POINTS: This is the first direct investigation into how the recognition of self-conscious emotion is affected in Parkinson's disease using dynamic, dual-intensity stimuli, thus providing an important extension to prior literature that has focused solely on basic emotion recognition and/or relied on static, high-intensity stimuli. Results revealed preserved basic facial emotional recognition coexisting with impairment in all three self-conscious emotions assessed, therefore suggesting that the latter stimuli type may function as a more sensitive indicator of Parkinson's disease-related social cognitive impairment. Problems with self-conscious emotion recognition in people with Parkinson's disease were associated with poorer broader subjective well-being and increased negative affect. This aligns with the broader literature linking interpersonal difficulties with poorer clinical outcomes in this cohort.

Tremor Drugs in the Crosshairs.

Background: Alopecia areata is a rare but debilitating adverse effect of drugs used in the treatment of tremors. Recurrent hair loss after different types of tremor medications has never been described before. Case Report: We herein report the case of a 56-year-old tremor patient who we diagnosed with tremor-dominant Parkinson's disease. Unfortunately, she developed acute alopecia areata following the introduction of firstly levodopa/benserazide, secondly propranolol, and thirdly topiramate. Discussion: Our case report highlights alopecia areata as a possible side effect to a variety of drugs commonly used for tremor management. Fortunately, in most reported cases, as well as in our case, the hair loss is reversible.

Driving restrictions following deep brain stimulation surgery.

BACKGROUND: There are currently no Australian guidelines to assist clinicians performing deep brain stimulation (DBS) procedures in setting postoperative driving restrictions. PURPOSE: We aimed to provide recommendations for post-DBS driving restrictions to guide practice in Australia. METHODS: A review of current Australian and international driving guidelines, literature regarding the adverse effects of DBS and literature regarding the long-term effect of neurostimulation on driving was conducted using Elton B Stephens Company discovery service-linked databases. Australian neurologists and neurosurgeons who perform DBS were surveyed to gain insight into existing practice. RESULTS: No guidance on driving restrictions following DBS surgery was found, either in existing driving guidelines or in the literature. There was a wide difference seen in the rates of reported adverse effects from DBS surgery. The most serious adverse events (haemorrhage, seizure and neurological dysfunction) were uncommon. Longer term, there does not appear to be any adverse effect of DBS on driving ability. Survey of Australian practitioners revealed a universal acceptance of the need for and use of driving restrictions after DBS but significant heterogeneity in how return to driving is managed. CONCLUSION: We propose a 6-week driving restriction for private licences and 6-month driving restriction for commercial licences in uncomplicated DBS. We also highlight some of the potential pitfalls and pearls to assist clinicians to modify these recommendations where needed. Ultimately, we hope this will stimulate further examination of this issue in research and by regulatory bodies to provide more robust direction for practitioners performing DBS implantation.

Psychogenic nonepileptic seizures treated as epileptic seizures in the emergency department.

OBJECTIVES: We aimed to estimate the rate of psychogenic nonepileptic seizures (PNES) among patients presenting to an emergency department with presumed seizures. We also wanted to identify factors that can assist health care professionals in determining whether these events are likely to be epileptic or nonepileptic. METHODS: We performed two retrospective audits on patients who were treated for seizures in the department of emergency medicine at the Princess Alexandra Hospital, Brisbane, Australia. Exploratory analyses and logistic regressions were conducted to investigate the characteristics of the presentations and the relationships between our variables of interest. RESULTS: In the group of all presentations with presumed seizures over a 3-month period (n = 157), a total of 151 presentations (96.2%) presentations were given a primary diagnosis of epileptic seizures. Of these 151 presentations, only 84 (55.6%) presented with epileptic seizures and 40 (26.5%) actually presented with PNES. In the group of patients who presented with prolonged and/or multiple events (n = 213) over a 1-year period, 196 (92.0%) were treated as epileptic seizures. Of these 196 presentations, only 85 (43.4%) presented with epileptic seizures and 97 (49.5%) actually presented with PNES. Several factors were identified to help risk stratify between epileptic seizures and PNES: Duration of events and of the postictal phase, number of events, presence of a structural brain pathology, mental health history, lactate levels and presence of tongue bite, incontinence, and/or vomiting. SIGNIFICANCE: A large proportion of people who present to emergency departments with events resembling epileptic seizures actually have PNES rather than epilepsy-particularly those patients who present with prolonged and/or multiple events. The rate of misdiagnosis was high. Efforts need to be made to recognize patients with psychogenic nonepileptic seizures earlier and diagnose them correctly to avoid unnecessary iatrogenic harm and to provide adequate treatment.

Exploring the Effect of Combined Transcranial and Intra-Oral Photobiomodulation Therapy Over a Four-Week Period on Physical and Cognitive Outcome Measures for People with Parkinson's Disease: A Randomized Double-Blind Placebo-Controlled Pilot Study.

BACKGROUND: Neuroprotection against Parkinson's disease degeneration by photobiomodulation has been reported in animal models but no true placebo-controlled human studies have been published. OBJECTIVE: To understand if photobiomodulation therapy can produce clinically significant differences in physical performance measures in people with Parkinson's disease; and what frequency of treatment is necessary to initiate clinical change. METHODS: In a participant and assessor-blinded, randomized, placebo-controlled pilot study, 22 participants received either sham and/or active laser photobiomodulation (904 nm, 60 mW/diode, 50 Hz) for 33 s to each of 21 points at the cranium and intra-orally, on one, two or three times/week for 4 weeks. Two treatment phases were separated by a 4-week wash-out (Phase 2). Upper and lower limb physical outcome measures were assessed before and after each treatment phase. The Montreal Cognitive Assessment was evaluated prior to treatment Phase 1, and at the end of treatment Phase 3. RESULTS: Montreal Cognitive Assessment remained stable between start and end of study. No measures demonstrated statistically significant changes. With regular treatment, the spiral (writing) test and the dynamic step test were most sensitive to change in a positive direction; and the 9-hole peg test demonstrated a minimum clinically important difference worthy of further investigation in a larger, adequately powered clinical trial. A placebo effect was noted. CONCLUSION: The results support the notion that combined transcranial and intra-oral photobiomodulation therapy needs to be applied at least 2 to 3 times per week for at least four weeks before some improvement in outcome measures becomes evident. Longer courses of treatment may be required.

Implicit motor imagery using laterality recognition in functional movement disorders.

Functional movement disorder (FMD) presents as disabling motor symptoms that cannot be explained by organic processes. Despite the lack of lesion or known central nervous system dysfunction, distortion in sensorimotor processing in movement generation and execution is often observed. A person's capacity to judge laterality of a body part requires processing of sensorimotor information. This prospective observational study compared reaction time (RT) and accuracy (ACC) of hand laterality recognition between 30 people diagnosed with FMD and 30 age-matched healthy control participants. The association of RT and ACC with severity of FMD as measured by the Simplified Functional Movement Disorders Rating Scale (SFMDRS) was also explored. RT was on average 0.6 s slower (95% CI 0.4 - 0.8 s, p < 0.001) in patients with FMD (mean 2.2 s, standard deviation (SD) 0.5) than controls (mean 1.7 s, SD 0.3). ACC was on average 8.9% lower (95% CI -15.7 - -2.2, p = 0.01) in patients with FMD (mean 79.6%, SD 16.6) than controls (mean 88.5%, SD 8.1). When adjusted for SFMDRS using robust regression, RT was 0.3 s slower (95% CI 0.01 - 0.5, p = 0.04) in cases than in controls, but ACC was no longer different between groups. There was a moderate negative correlation between RT and ACC in FMD patients (ρ -0.58, p < 0.001 but not in controls (ρ -0.26, p = 0.17). People with FMD had significantly slower RT and lower ACC compared to the control group. These results provide new insights into underlying sensorimotor processing deficits in those with FMD.

Differentiating psychogenic nonepileptic seizures from epileptic seizures: An observational study of patients undergoing video-electroencephalography (VEEG) in Australia.

Video-electroencephalography (VEEG) is an invaluable tool for the differentiation of psychogenic nonepileptic seizures (PNES) from epileptic seizures (ES). This paper (i) evaluates the demographics of patients undergoing VEEGs at the Princess Alexandra Hospital from July 1 2017 to July 1 2019 and identifies those subsequently diagnosed with PNES, (ii) determines the delay in PNES diagnosis and proportion of PNES patients on antiepileptic drugs (AEDs) prior to a VEEG, and (iii) determines the proportion of PNES patients who subsequently ceased their AEDs. Of the 94 patients in the study group, 51 were female and 43 were male. In total, 22 (23%) of VEEGs were consistent with epilepsy (ES), 25 (26%), with PNES, 5 (5%) mixed (PNES and ES), 5 (5%) with other types of events, and 37 were nondiagnostic. Two patients with non-diagnostic VEEGs were subsequently treated as PNES at the treating clinician's discretion. Regarding AEDs, 62 of the patients were on at least one agent at the time of VEEG recording. The mean durations of AED therapy and diagnostic delay for patients subsequently diagnosed with PNES were six years and seven years, respectively. Of these, the majority had their AEDs subsequently weaned/ceased. This study highlights the value of VEEG in diagnostic differentiation of epileptic from nonepileptic events, thereby preventing unnecessary AED therapy for patients with PNES. The results are consistent with previous studies in the literature evaluating VEEG clinical outcomes.