INTRODUCTION:Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson's disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia. OBJECTIVES:To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured with a wearable device. METHODS:In this cross-sectional study, ICB and other neuropsychiatric symptoms were assessed by means of structured clinical interview and specific screening instruments. Presence and severity of motor fluctuations and dyskinesia were rated with patient's and clinician's based rating instruments. Motor fluctuations and dyskinesia were also measured at home for 5-days using a validated wearable devise, the Parkinson's KinetiGraph™(PKG). RESULTS:We included 89 subjects with PD (29 females, 62 ± 7 years, disease duration 10.3 ± 4.5), of whom 36 (40%) had ICB. Patients with and without ICB did not differ by presence and severity of dyskinesia measured by clinical scales and PKG. There was no association between the presence of ICB and dyskinesia in the whole sample. CONCLUSION:Our data suggest that ICB and dyskinesia are common but unrelated disorders in advanced PD.

ObjectivesImpulsive compulsive behaviour disorders (ICB) and dyskinesia are common and disabling complications occurring during the course of Parkinson’s disease (PD). Their pathophysiology is not clear yet, however an association has been suggested. In the present study we aimed to evaluate the relationship between the presence of dyskinesia objectively detected using a wearable device and the presence of active and past ICB in PD patients.MethodsPatients’ demographic and clinical characteristics were gathered, PD medications were converted in total levodopa equivalent daily dose (LEDD) and LEDD dopamine-agonists. Patients were assessed with: Unified PD Rating Scale (UPDRS) parts I-IV and Rusk Dyskinesia Rating Scale (RDRS). To objectively measure dyskinesia we used a wearable devise, the Parkinson’s KinetiGraph™ system (PKG®), an accelerometry-based system for automated assessment of dyskinesia and bradykinesia. Past and active ICB were diagnosed with a semi-structured interview.Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS) was employed to rate ICB severity. Psychiatric symptoms were evaluated including depression, anxiety, apathy and impulsivity.ResultsFifty-five PD patients were evaluated (36 males, mean age 60.7±6.7; mean disease duration 10.5±4.9). Twenty-five patients (45%) had dyskinesia as per PKG ‘Percent Time in Dyskinesia’ score. Nineteen patients had ICB (34%). There was no difference in active/past ICB between patients with and without dyskinesia (p=0.8 and 0.6). Patients with dyskinesia had higher LEDD dopamine-agonists (p=0.005), UPDRS-IV (p=0.02), RDRS (p=0.002). There was no difference between groups in psychiatric symptoms. We categorized patients in 3 groups (none, mild/moderate and severe dyskinesia) and we found no difference among groups in any demographic, clinical, psychiatric and behavioural variable except for LEDD dopamine-agonists (p=0.004), UPDRS-IV (p=0.06), RDRS (p=0.004).Binary regression analysis did not show any association between the presence of dyskinesia and ICB, depression, anxiety, apathy and impulsivity.ConclusionOur data suggest that ICB and dyskinesia are common but unrelated disorders in PD.

Background Depression is the most common, though often under-recognised, neuropsychiatric disturbance in movement disorders (MD). Objective This study aimed to establish whether a briefer screening measure such as a visual analogue screening measure (Emotions Thermometer) or Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) could be a potentially suitable screening tool for depression in MD patients. Method Patients attending a regional MD outpatient clinic completed the Emotional Thermometer 7-item tool (ET7), the Hospital Anxiety and Depression Scale (HADS) and the Neurological Disorders Depression Inventory for Epilepsy (NDDIE). We used the Major Depression Inventory which provided the diagnosis of depression based on ICD-10 and DSM-IV as our diagnostic gold standard to compare the performance of ET7 and its individual sub-scales, its briefer version ET4, HADS, and NDDIE. Sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic curves were calculated to compare the performance of the screening tools. Results In total, 188 patients were included in the analysis. The most accurate tools as determined by Receiver Operating Characteristics curve were HADS-D for ICD-10 depressive episode and DepT for DSM-IV major depression. ET4 performed well as a 'rule-out' screening tool for both DSM-IV and ICD-10 depression. ET4 performance was comparable to HADS without the need for clinician scoring. The briefer ET4 performed almost as well as ET7. Conclusion Emotions Thermometer and NDDI-E are quick and reliable screening tools for depression in the MD population and are comparable to HADS. We suggest routine use of visual analogue ET4 as it is briefer, requires less time to complete and does not require scoring from the clinicians. It has the potential to be widely implemented across busy neurology clinics to assist in depression screening.

Teleneurology and telephone consultations have long been used in neurology.1 2 There is a lack of research data on using remote consultations for new neurology outpatients and only low-level evidence for their use in general practice. Remote consultations provide a mechanism for neurology care during the COVID-19 pandemic. Switching from face-to-face new appointments to remote (telephone or video) consultations allows continued provision of neurological services to patients while reducing hospital footfall; this could limit the spread of COVID-19 and avoid exposing vulnerable patients who attend the clinic to unnecessary risk.\n\nWe have built this document using advice from the UK General Medical Council (GMC) on remote consultations.3 However, the GMC’s advice is not wholly applicable in the setting of COVID-19; their safety concerns are mostly mitigated by the fact that we are the patient’s regular healthcare provider, with access to their notes and referral letters. The GMC also makes specific provision for departure from established procedures to care for patients in the highly challenging but time-bound circumstances of the peak of an epidemic.3 \n\nGiven that the clinical history provides the greatest part of the information that leads to a diagnosis,4 remote consultation should be able to help many patients. In general practice, remote consultations were not associated with any statistically significant change in visits to the Emergency Department or any differences in rates of admissions or of patient satisfaction.5 However, remote consultations have been linked to more repeated visits: an average of two additional contacts for every 10 patients.6 Although a quarter of all patient consultations now occur on the telephone in general practice, there is no evidence base upon which to inform clinician training in this skill.7 This paper aims to help neurologists to conduct remote consultations, particularly in relation to the current …

The authors wish to make the following erratum to this paper [...].

Background Little research has been conducted regarding the relationship between sleep disorders and different pain types in Parkinson's disease (PD). Objective To explore the influence of the various pain subtypes experienced by PD patients on sleep. Methods Three hundred consecutive PD patients were assessed with the PD Sleep Scale-Version 2 (PDSS-2), King's PD Pain Scale (KPPS), King's PD Pain Questionnaire (KPPQ), Visual Analog Scales for Pain (VAS-Pain), and Hospital Anxiety and Depression Scale. Results According to the PDSS-2, 99.3% of our sample suffered from at least one sleep issue. Those who reported experiencing any modality of pain suffered significantly more from sleep disorders than those who did not (all, P < 0.003). The PDSS-2 showed moderate-to-high correlations with the KPPS (r(S) = 0.57), KPPQ (0.57), and VAS-Pain (0.35). When PDSS-2 items 10 to 12 (pain-related) were excluded, the correlation values decreased to 0.50, 0.51, and 0.28, respectively, while these items showed moderate-to-high correlations with KPPS (0.56), KPPQ (0.54), and VAS-Pain (0.42). Among the variables analyzed, multiple linear regression models suggested that KPPS and KPPQ were the most relevant predictors of sleep disorders (as per the PDSS-2), although following exclusion of PDSS-2 pain items, depression was the relevant predictor. Depression and anxiety were the most relevant predictors in the analysis involving the VAS-Pain. Regression analysis, considering only the KPPS domains, showed that nocturnal and musculoskeletal pains were the best predictors of overall nocturnal sleep disorder. Conclusions Pain showed a moderate association with nocturnal sleep dysfunction in PD. Some pain subtypes had a greater effect on sleep than others.

The response to levodopa (LR) is important for managing Parkinson's Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson's Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies.

Objectives: MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP.Methods: Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n = 21), Parkinson disease (n = 10), MSA (n = 10), and controls (n = 21).Results: The mean midbrain measurement of 8.1 mm was reduced in PSP (p < 0.001) with reduction in the midbrain to pons ratio (PSP smaller than MSA; p < 0.001). In controls, the mean midbrain ratio was approximately two-thirds of the pontine base, in PSP it was <52%, and in MSA the ratio was greater than two-thirds. A midbrain measurement of <9.35 mm and ratio of 0.52 had 100% specificity for PSP. In the clinically defined group, 19 of 21 PSP cases (90.5%) had a midbrain measurement of <9.35 mm.Conclusions: We have developed a simple and reliable measurement in pathologically confirmed disease based on the topography of atrophy in PSP with high sensitivity and specificity that may be a useful tool in the clinic.

The reasons for the differences in emphasis on striatonigral or olivopontocerebellar involvement in multiple system atrophy (MSA) remain to be determined. Semi-quantitative pathological analyses carried out in the United Kingdom and Japan demonstrated that olivopontocerebellar-predominant pathology was more frequent in Japanese MSA than British MSA. This observation provides evidence for a difference in phenotype distribution between British and Japanese patients with definite MSA. Studies of the natural history and epidemiology of MSA carried out in various populations have revealed that the relative prevalences of clinical subtypes of MSA probably differ among populations; the majority of MSA patients diagnosed in Europe have predominant parkinsonism (MSA-P), while the majority of MSA patients diagnosed in Asia have predominant cerebellar ataxia (MSA-C). Although potential drawbacks to the published frequencies of clinical subtypes and pathological subtypes should be considered because of selection biases, the difference demonstrated in pathological subtype is also consistent with the differences in clinical subtype of MSA demonstrated between Europe and Asia. Modest alterations in susceptibility factors may contribute to the difference in MSA phenotype distribution between populations. Synergistic interactions between genetic risk variants and environmental toxins responsible for parkinsonism or cerebellar dysfunction should therefore be explored. Further investigations are needed to determine the environmental, genetic, and epigenetic factors that account for the differences in clinicopathological phenotype of MSA among different populations.

Conventional magnetic resonance imaging (cMRI) is often used to aid the diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), but its ability to predict the histopathological diagnosis has not been systematically studied. cMRI from 48 neuropathologically confirmed cases, including PSP (n = 22), MSA (n = 13), Parkinson's disease (PD) (n = 7), and corticobasal degeneration (n = 6), and controls (n = 9) were assessed blinded to clinical details and systematically rated for reported abnormalities. Clinical diagnosis and macroscopic postmortem findings were retrospectively assessed. Radiological assessment of MRI was correct in 16 of 22 (72.7%) PSP cases and 10 of 13 (76.9%) MSA cases with substantial interrater agreement (Cohen's kappa 0.708; P < .001); no PSP case was misclassified as MSA or vice versa. MRI was less sensitive but more specific than clinical diagnosis in PSP and both more sensitive and specific than clinical diagnosis in MSA. The "hummingbird" and "morning glory" signs were highly specific for PSP, and "the middle cerebellar peduncle sign" and "hot cross bun" for MSA, but sensitivity was lower (up to 68.4%) and characteristic findings may not be present even at autopsy. cMRI, clinical diagnosis, and macroscopic examination at postmortem have similar sensitivity and specificity in predicting a neuropathological diagnosis. We have validated specific radiological signs in pathologically confirmed PSP and MSA. However, the low sensitivity of these and macroscopic findings at autopsy suggest a need for imaging techniques sensitive to microstructural abnormalities without regional atrophy.

Background: MAPT mutations are associated with disorders within the frontotemporal lobar degeneration spectrum. The usual presenting syndrome is behavioural variant frontotemporal dementia, although some patients present with parkinsonism. In a number of these cases the dominant clinical features have been consistent with a progressive supranuclear palsy (PSP) syndrome. Objective: To describe a family with an autosomal dominant PSP syndrome with a novel L284R mutation in the MAPT gene. Methods: A retrospective case review and genetic analysis of the MAPT gene. A literature review of PSP syndromes associated with mutations in the MAPT gene. Results: Multiple members of family DRC292 across different generations had a PSP syndrome with 1 member of the family being found to have a novel L284R mutation in the MAPT gene. Behavioural features were also prominent in most cases. A PSP syndrome is only a rare finding associated with MAPT mutations and many of these cases have atypical clinical features. Conclusion: Although rare, MAPT mutations should be considered when there is an autosomal dominant family history of a PSP syndrome, particularly of young onset and with prominent behavioural features.

A 13‐year old girl presented with slowly progressive rest tremor of the hands, bradykinesia, and rigidity. The symptoms improved with dopaminergic medications, but severe drug‐induced dyskinesias developed early. She subsequently developed cognitive slowing and difficulty initiating saccadic eye movements. She went on to have deep brain stimulation surgery. Experts discuss the syndromal diagnosis and predict the underlying pathology. The pathological diagnosis is given and clinical learning points are considered. © 2010 Movement Disorder Society

There is currently considerable interest in the clinical spectrum of progressive nonfluent aphasia (PNFA) and progressive supranuclear palsy (PSP) and the intersection of these two entities. Here, we undertook a detailed prospective clinical, neuropsychological, and neuroimaging analysis of 14 consecutive patients presenting with PNFA to identify cases meeting clinical criteria for PSP. These patients had further detailed assessment of extrapyramidal and oculomotor functions. All patients had high-resolution MR brain volumetry and a cortical thickness analysis was undertaken on the brain images. Four patients presenting with PNFA subsequently developed features of a PSP syndrome, including a typical oculomotor palsy. The neuropsychological profile in these cases was similar to other patients with PNFA, however, with more marked reduction in propositional speech, fewer speech errors, less marked impairment of literacy skills but more severe associated deficits of episodic memory and praxis. These PSP-PNFA cases had less prominent midbrain atrophy but more marked prefrontal atrophy than a comparison group of five patients with pathologically confirmed PSP without PNFA and more prominent midbrain atrophy but less marked perisylvian atrophy than other PNFA cases. In summary, although the PSP-PNFA syndrome overlaps with PNFA without PSP, certain neuropsychological and neuroanatomical differences may help predict the development of a PSP syndrome.

A 13-year old girl presented with slowly progressive rest tremor of the hands, bradykinesia, and rigidity. The symptoms improved with dopaminergic medications, but severe drug-induced dyskinesias developed early. She subsequently developed cognitive slowing and difficulty initiating saccadic eye movements. She went on to have deep brain stimulation surgery. Experts discuss the syndromal diagnosis and predict the underlying pathology. The pathological diagnosis is given and clinical learning points are considered. (C) 2010 Movement Disorder Society

The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity = 26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (> 3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal degeneration cases presented clinically with a progressive supranuclear palsy phenotype and 29% of cases with corticobasal syndrome had underlying progressive supranuclear palsy pathology. In contrast, in the Queen Square Brain Bank archival collection, corticobasal syndrome is a rare clinical presentation of progressive supranuclear palsy occurring in only 6 of the 179 pathologically diagnosed progressive supranuclear palsy cases (3%). Despite these diagnostic difficulties we conclude that corticobasal degeneration is a discrete clinicopathological entity but with a broader clinical spectrum than was originally proposed.

Background Although conventional MRI (cMRI) has been reported to show specific abnormalities in parkinsonism, the diagnosis of the underlying pathology can be challenging. We report the radiological diagnostic accuracy, and the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of cMRI abnormalities in a pathologically confirmed cohort of Parkinson9s disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration (CBD). Method cMRI of donors to a neurological brain bank was reviewed by two experienced neuroradiologists blinded to clinical details. Images were systematically reviewed for the presence of specific reported abnormalities. Results 48 pathologically confirmed cases (23 PSP, 6 PD, 13 MSA and 6 CBD) and nine controls were studied. The final clinical diagnosis was supported in 68% and the radiological diagnosis in 60%. Using cMRI 55% of PSP, 67% of PD, and 77% of MSA were correctly identified. In this study the Hummingbird sign has 68% sensitivity, 100% specificity and PPV for PSP and the Hot Cross Bun has 62% sensitivity, 100% specificity and PPV for MSA. Conclusion The confirmation that using cMRI key diagnostic features with very high specificity and PPV have low sensitivity endorses the development of newer MR techniques (e.g., high field diffusion tensor imaging) as useful biomarkers early in disease.

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease‐modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann‐Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson–dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

Progressive supranuclear palsy (PSP) and multiple system (MSA) atrophy are associated with progressive brain atrophy. Serial MRI can be applied in order to measure this change in brain volume and to calculate atrophy rates.We evaluated MRI derived whole brain and regional atrophy rates as potential markers of progression in PSP and the Parkinsonian variant of multiple system atrophy (MSA-P).17 patients with PSP, 9 with MSA-P and 18 healthy controls underwent two MRI brain scans. MRI scans were registered, and brain and regional atrophy rates (midbrain, pons, cerebellum, third and lateral ventricles) measured. Sample sizes required to detect the effect of a proposed disease-modifying treatment were estimated. The effect of scan interval on the variance of the atrophy rates and sample size was assessed.Based on the calculated yearly rates of atrophy, for a drug effect equivalent to a 30% reduction in atrophy, fewer PSP subjects are required in each treatment arm when using midbrain rather than whole brain atrophy rates (183 cf. 499). Fewer MSA-P subjects are required, using pontine/cerebellar, rather than whole brain atrophy rates (164/129 cf. 794). A reduction in the variance of measured atrophy rates was observed with a longer scan interval.Regional rather than whole brain atrophy rates calculated from volumetric serial MRI brain scans in PSP and MSA-P provide a more practical and powerful means of monitoring disease progression in clinical trials.

Progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple-system atrophy (MSA-P) may present with a similar phenotype. Magnetic resonance diffusion-weighted imaging (DWI) has been shown to be a sensitive discriminator of MSA-P from Parkinson's disease (PD). We studied 20 PSP, I I MSA-P, 12 PD patients and 7 healthy controls in order to investigate whether regional apparent diffusion coefficients (rADCs) help distinguish PSP and MSA-P; whether rADCs are correlated with clinical disease severity scores; and the relationship between brainstem and cerebellar volumes and rADCs in PSP and MSA-P. The Unified Parkinson's Disease Rating Scale, Hoehn and Yahr score, Mini Mental State Examination, and frontal assessment battery were recorded in all patients. Regional ADCs were measured in the middle cerebellar peduncle (MCP), caudal and rostral pons, midbrain, decussating fibers of the superior cerebellar peduncle, thalamus, putamen, globus pallidus, caudate nucleus, corpus callosum, frontal and parietal white matter, as well as the centrum semiovale. In MSA-P, rADCs in the MCP and rostral pons were significantly greater than in PSP (P < 0.001 and 0.009) and PD (P < 0.001 and = 0.002). Stepwise logistic regression revealed that the MCP rADC distinguishes MSA-P from PSP with a sensitivity of 91% and a specificity of 84%. Increased brainstem rADCs were associated with motor deficit in MSA-P and PSP. Increased rADCs in the pons and MCP were associated with smaller pontine and cerebellar volumes in MSA-P. rADCs distinguish MSA-P from PSP. These have a clinical correlate and are associated with reduced brainstem and cerebellar volumes. (C) 2006 Movement Disorder Society.

Holmes tremor has a characteristic rest, intention, and postural component. The syndrome arises as a consequence of a lesion in the upper brainstem and cerebral peduncles, which, it is postulated, interrupts the cerebello‐rubrothalamic pathway. Ataxia, ophthalmoplegia, and bradykinesia are associated features. We present a case of Holmes tremor secondary to a midbrain cavernoma. Modern neuroimaging techniques in this case confirm that a combination of damage to the cerebello‐rubrothalamic pathway and the nigrostriatal pathway is required for the full Holmes tremor syndrome to occur. © 2006 Movement Disorder Society