ABSTRACT Background Impulse control behaviors (ICBs) are problematic, reward‐based behaviors, affecting 15% to 35% of patients with Parkinson's disease. Evidence exists of increased carer burden as a result of these behaviors; however, little is known about the variables mediating this effect and their management. Objective To identify factors predictive of carer burden in a cohort of patients with Parkinson's disease with ICBs to enable the development of targeted therapeutic interventions for carers. Methods Data were collected from 45 patients with clinically significant ICBs and their carers, including levodopa equivalent daily dosage, motor and neuropsychiatric symptoms, cognitive function, and ICB severity. Carer burden was quantified by Zarit Burden Interview (ZBI). Univariate analyses were performed using the Spearman rank correlation. Linear regression was used to create a multivariate model for predicting ZBI. Results Univariate analysis identified significant correlations between ZBI and patient total Neuropsychiatric Inventory (NPI) ( r s = 0.50), 4 NPI subscores (agitation/aggression, r s = 0.41; depression/dysphoria, r s = 0.47; apathy/indifference, r s = 0.49; and irritability/lability, r s = 0.38; all P < 0.02), and the carer 28‐item General Health Questionnaire (GHQ‐28) ( r s = 0.52, P < 0.0005). Multivariate linear regression retained total NPI and GHQ‐28 scores and were collectively predictive of 36.6% of the variance in the ZBI. Conclusions Our study suggests that depressive symptoms and aspects of executive dysfunction (apathy and disinhibition) in the patient are potential drivers of carer burden in patients with ICBs. Such findings suggest the presence of executive difficulties and/or mood disturbance should point the clinician to inquire about burden in the caring role and encourage the carer to seek help for any of their own general health problems, which may compound carer burden.

Background: In clinical trials that recruited patients with early Parkinson’s disease (PD), 4–15% of the participants with a clinical diagnosis of PD had normal dopamine transporter single photon emission computed tomography (DAT SPECT) scans, also called “scans without evidence of dopaminergic deficit” (SWEDD). Objective: To investigate in patients with a clinical diagnosis of PD, if specific clinical features are useful to distinguish patients with nigrostriatal degeneration from those that have no nigrostriatal degeneration. Methods: We performed a diagnostic test accuracy study. Patients that participated in the Levodopa in Early Parkinson’s disease trial, a clinical trial in patients with early PD, were asked to participate if they had not undergone DAT SPECT imaging earlier. The index tests were specific clinical features that were videotaped. A panel of six neurologists in training (NT), six general neurologists (GN), and six movement disorders experts (MDE) received a batch of ten videos consisting of all SWEDD subjects and a random sample of patients with abnormal DAT SPECT scans. The raters analyzed the videos for presence of specific signs and if they suspected the patient to have SWEDD. The reference test was visually assessed DAT SPECT imaging. Results: Of a total of 87 participants, three subjects were SWEDDs (3.4%). The overall intraclass correlation coefficient (ICC) of the Parkinsonian signs was poor to moderate with ICCs ranging from 0.14 to 0.67. NT correctly identified 50.0% of the SWEDD subjects, GN 33.3%, and MDE 66.7%. Conclusion: Our study suggests that the selected videotaped clinical features cannot reliably distinguish patients with a clinical diagnosis of PD and an abnormal DAT SPECT from patients with clinical PD and a SWEDD.

Objective To assess the uptake of hormone replacement therapy in women living with HIV (WLHIV) in particular acceptability, response to treatment and compliance. Study design Retrospective review of menopausal women attending a HIV medical gynaecology clinic in a tertiary referral London Hospital between 1 January 2011 and 31 December 2016. Main outcome measures Patient demographics, presenting symptoms, uptake of hormone replacement therapy, type of hormone replacement therapy used and bone density assessment findings at presentation. Results Seventy-three HIV patients were evaluated. Of them 64 (87%) were of black ethnicity and 9 (13%) were of white ethnicity. The commonest presenting complaints were vasomotor symptoms (40/73, (55%)) followed by low mood/irritability (20/73, (27%)). When offered hormone replacement therapy, this was accepted by 28/53 (52%) in WLHIV. The commonest regimen prescribed was transdermal oestradiol/micronised progesterone. A total of 22/24 (91%) women of black ethnicity reported good symptom control if they had started hormone replacement therapy, with 4/24 (17%) subsequently discontinuing it; 3/4 (75%) of white women reported good symptom control with hormone replacement therapy, with no one discontinuing it. The commonest reason for discontinuation was irregular bleeding. Of WLHIV who had a bone density assessment, 15/25 (60%) had osteopenia while 2/25 (8%) had osteoporosis. Conclusion Our data show that only around 50% WLHIV accepted hormone replacement therapy when offered and a high proportion of these women discontinued it. Further research is needed to explore the reason leading to low uptake and high rates of stopping hormone replacement therapy. In addition, there is a need to increase awareness of the benefits of hormone replacement therapy in WLHIV both in the context of preventing osteoporosis and menopausal symptom management.

Non-motor symptoms of Parkinson's disease have a significant impact on quality of life. Despite this, many non-motor symptoms remain unreported by patients and consequently untreated. This study explored barriers to help-seeking using two theoretical frameworks, the Common Sense Model of illness perception and Theoretical Domains Framework. A total of 20 participants completed semi-structured interviews to explore symptom beliefs and help-seeking behaviour. Uncertainty about the relationship of non-motor symptoms to Parkinson's disease and lack of clarity around treatments were common. Embarrassment and communication difficulties were common for potentially sensitive symptoms such as sexual dysfunction. Symptom perceptions and beliefs about help-seeking acted as barriers to reporting non-motor symptoms.

Background Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The present study aimed to i) further assess the prevalence of NMS and associated distress, ii) establish current rates of NMS reporting across a range of sources, and iii) explore overall and any symptom specific barriers to help-seeking for NMS. Methods 358 PD patients completed a cross-sectional survey of NMS severity, reporting and barriers to help-seeking. A series of Generalised Estimating Equations were used to determine whether barriers were symptom specific. Results A mean of 10.5 NMS were reported by each patient. Rates of non-reporting of NMS ranged from 15 to 72% of those experiencing distressing symptoms. The most commonly reported barriers to help-seeking were acceptance of symptoms; lack of awareness that a symptom was associated with PD, and belief that no effective treatments were available. Symptom specific barriers were found for sexual dysfunction (embarrassment), unexplained pain and urinary problems (belief about lack of treatment availability). Conclusion A diverse range of barriers prevent PD patients reporting NMS to HCPs and these barriers differ between NMS. The study provides the foundations for developing interventions to increase reporting by targeting individual NMS. Increasing rates of help-seeking for NMS by patients to their Parkinson's healthcare providers will increase appropriate clinical care which may improve quality of life and well-being.

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS. Objective: To investigate the impact of active contact location on NMS in STN-DBS in PD. Methods: In this prospective, open-label, multicenter study including 50 PD patients undergoing bilateral STN-DBS, we collected NMSScale (NMSS), NMSQuestionnaire (NMSQ), Hospital Anxiety and Depression Scale (anxiety/depression, HADS-A/-D), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD-motor examination, motor complications, activities of daily living (ADL), and levodopa equivalent daily dose (LEDD) preoperatively and at 6 months follow-up. Changes were analyzed with Wilcoxon signed-rank/t-test and Bonferroni-correction for multiple comparisons. Although the STN was targeted visually, we employed an atlas-based approach to explore the relationship between active contact locations and DBS outcomes. Based on fused MRI/CT-images, we identified Cartesian coordinates of active contacts with patient-specific Mai-atlas standardization. We computed linear mixed-effects models with x-/y-/z-coordinates as independent, hemispheres as within-subject, and test change scores as dependent variables. Results: NMSS, NMSQ, PDQ-8, motor examination, complications, and LEDD significantly improved at follow-up. Linear mixed-effect models showed that NMS and QoL improvement significantly depended on more medial (HADS-D, NMSS), anterior (HADS-D, NMSQ, PDQ-8), and ventral (HADS-A/-D, NMSS, PDQ-8) neurostimulation. ADL improved more in posterior, LEDD in lateral neurostimulation locations. No relationship was observed for motor examination and complications scores. Conclusions: Our study provides evidence that more anterior, medial, and ventral STN-DBS is significantly related to more beneficial non-motor outcomes.

Cognitive deficits and psychiatric morbidities are commonly detected in dystonia. Psychiatric disturbances are of particular clinical concern as they not only contribute to poor quality of life and disease associated burden, but also exacerbate motor and cognitive symptoms. Bilateral deep brain stimulation of the globus pallidus internus improves motor symptoms in treatment-resistant dystonia, but its implications for non-motor manifestations are poorly understood. Improved prediction of cognitive and neuropsychiatric outcomes is important in deep brain stimulation (DBS) research and we aim to assess the latter through established assessment tools. We document the cognitive and neuropsychiatric profiles in 11 primary and 10 secondary dystonia patients attending our DBS clinic. We performed routine multidisciplinary assessments including a comprehensive battery of neuropsychometric tests and detailed neuropsychiatric evaluations. Post-operative assessment outcomes are reported for three patients in case series. The main cognitive deficit was on the Brixton test of spatial anticipation in primary dystonia. Background medical history included psychiatric illness in 38.1% of the patients with 76% of patients having mood abnormalities confirming elevated psychiatric morbidity in this population. Depressive illness was more prominent in primary, whereas clinically relevant histories in secondary dystonia were varied. Of the 21 patients three were able to perform on selected tests due to extensive limitations of their dystonia. No obvious alteration in intellectual functioning following DBS surgery relative to performance at the time of initial assessment was observed. The frequency of individual impairments suggests that difficulties associated with dystonia are likely to be of clinical relevance to cognitive functions in the majority of patients. In particular, current findings suggest that executive difficulties related to inductive processes and spatial learning may be a common in primary dystonias. Psychiatric disturbances demand recognition as a central aspect of dystonia as they contribute to overall disease burden, poor quality of life and exacerbated motor disabilities. The available evidence provides overwhelming suggestion that vulnerability to depression is inherent to the dystonia phenotype.

We report two patients with anti-myelin-associated glycoprotein (MAG) neuropathy who experienced significant acute and persistent worsening of tremor after rituximab treatment. Anti-MAG neuropathy is an antibody-mediated chronic sensorimotor demyelinating neuropathy associated with an IgM-paraprotein. The typical clinical picture is sensory ataxia and distal numbness. Tremor is common [ [1] Bain P.G. Britton T.C. Jenkins I.H. Thompson P.D. Rothwell J.C. Thomas P.K. Brooks D.J. Marsden C.D. Tremor associated with benign IgM paraproteinaemic neuropathy. Brain. 1996; 119: 789-799 Crossref PubMed Scopus (128) Google Scholar ], and sometimes very disabling [ 2 McMaster J. Gibson G. Castro-Prado F. Vitali A. Honey C.R. Neurosurgical treatment of tremor in anti-myelin-associated glycoprotein neuropathy. Neurology. 2009; 73 (1707–8.18) Crossref PubMed Scopus (17) Google Scholar , 3 Bayreuther C. Delmont E. Borg M. Fontaine D. Deep brain stimulation of the ventral intermediate thalamic nucleus for severe tremor in anti-MAG neuropathy. Mov. Disord. 2009; 24: 2157-2158 Crossref PubMed Scopus (21) Google Scholar , 4 Latino P. Pellicano C. Pontieri F.E. Giovannelli M. Treatment with botulinum toxin for anti-MAG neuropathy-related arm tremor. Neurol. Sci. 2015; 36: 333-334 Crossref PubMed Scopus (6) Google Scholar ]. Treatment of the neuropathy and the tremor remains challenging. There was low quality evidence of benefit from rituximab in a meta-analysis of two randomised trials [ [5] Lunn M.P. Nobile-Orazio E. Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies. Cochrane Database Syst. Rev. 2016; 10CD002827 PubMed Google Scholar ]. Eighteen cases of deterioration in neuropathy after rituximab have been reported [ 6 Sala E. Rovert-Varvat F. Paul S. Camdessanché J.P. Antoine J.C. Acute neurological worsening after rituximab treatment in patients with anti-MAG neuropathy. J. Neurol. Sci. 2014; 345: 224-227 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar , 7 Vo M.L. Martin P. Latov N. Correlation of changes in gait parameters, with phenotype, outcome measures, and electrodiagnostic abnormalities in a patient with anti-MAG neuropathy after exacerbation and improvement. J. Clin. Neuromuscul. Dis. 2015; 17: 22-26 Crossref PubMed Scopus (7) Google Scholar , 8 Gironi M. Saresella M. Ceresa L. Calvo M. Ferrante P. Merli F. Nemni R. Clinical and immunological worsening in a patient affected with Waldenstrom macroglobulinemia and anti-mag neuropathy after treatment with rituximab. Haematologica. 2006; 91ECR17 PubMed Google Scholar , 9 Not A. Labeyrie C. Beaudonnet G. Chretien P. De Jorna R. Théaudin M. Cauquil C. Adams D. Experience of rituximab for anti MAG neuropathy: a monocentric study. J. Peripher. Nerv. Syst. 2015; 20 (abstract): 88-253 Crossref Google Scholar ], although only one of these had worsening of tremor [ [8] Gironi M. Saresella M. Ceresa L. Calvo M. Ferrante P. Merli F. Nemni R. Clinical and immunological worsening in a patient affected with Waldenstrom macroglobulinemia and anti-mag neuropathy after treatment with rituximab. Haematologica. 2006; 91ECR17 PubMed Google Scholar ]. In the two randomised trials of rituximab, a few patients worsened but it is not stated whether the speed of worsening was more rapid than before treatment [ 10 Dalakas M.C. Rakocevic G. Salajegheh M. Dambrosia J.M. Hahn A.F. Raju R. McElroy B. Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein antibody demyelinating neuropathy. Ann. Neurol. 2009; 65: 286-293 Crossref PubMed Scopus (236) Google Scholar , 11 Léger J.M. Viala K. Nicolas G. Créange A. Vallat J.M. Pouget J. Clavelou P. Vial C. Steck A. Musset L. Marin B. RIMAG Study Group (France and Switzerland) Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. Neurology. 2013; 80: 2217-2225 Crossref PubMed Scopus (137) Google Scholar ]. Case 1: A 72 year-old Caucasian man presented with distal weakness and wasting in all limbs, ataxia, and severe upper limb postural and intention tremor, which had all developed slowly over 25 years. He had no family history of tremor. He was diagnosed with anti-MAG neuropathy, but neither the neuropathy nor the tremor improved after intravenous immunoglobulin (IVIg) 2 g/kg or a course of predisolone. He then worsened rapidly in the two years prior to rituximab therapy. Bone marrow aspirate and trephine, and CT chest, abdomen and pelvis were normal, suggesting monoclonal gammopathy of uncertain significance (MGUS). Nerve conduction studies (NCS) showed evidence of severe demyelinating neuropathy with significantly prolonged distal latencies and secondary axonal degeneration. Before rituximab, he had an IgM-kappa paraprotein of 6.1 g/L, with total serum IgM 11.3 g/L, and anti-MAG antibody titre >70.000 BTU (Buehlmann Titer Units, normal below 1000 BTU). Neurological examination showed MRC (Medical Research Council) sum score of 53/70. He then received four infusions of rituximab 375 mg/m2 at one week intervals. A few days after the last infusion, his tremor significantly worsened and extended to affect the trunk. His weakness, balance and gait deteriorated. He became unable to hold a pen or write, and needed the aid of a person when walking. Five months after treatment, he had deteriorated further and MRC sum score was worse at 51/70. The paraprotein concentration did not change significantly (measured five times in the first year after rituximab). Brain MRI was normal. Sixteen months after rituximab he underwent plasma exchange (five exchanges on alternate days) which gave a transient fall in paraprotein level to 1.3 g/L and very slight improvement in walking but not tremor. NCS were not repeated. Tremor did not respond to primidone (750 mg/day) or propanolol (240 mg/day). Case 2: A 76 year-old Caucasian man presented with two years of numbness in the feet, unsteady gait, and a severe postural and intention tremor in both hands, right worse than left. He was diagnosed with an anti-MAG neuropathy, and received prednisolone for 18 months without improvement. He mainly ate with a spoon and his wife had to cut his food for him. Alcohol lessened his tremor. He had no family history of tremor. Examination showed severe postural and intention tremor in both hands, reduced light touch and pinprick sensation distal to the fingers and knees symmetrically, reduced joint position sensation at the toes bilaterally and positive Romberg's test. MRC sum score was 61/70. NCS showed evidence of severe demyelinating neuropathy with significantly prolonged distal latencies. Before rituximab he had an IgM-kappa paraprotein of 2 g/L, and anti-MAG antibody titre >7000 BTU. Bone marrow biopsy and CT chest, abdomen and pelvis were normal suggesting MGUS. He received rituximab 375 mg/m2 weekly for four weeks then monthly for two months. After the second infusion, his tremor started to worsen rapidly. After the sixth infusion, IgM-kappa paraprotein concentration was 2.34 g/L. Due to the deterioration of the tremor his wife had to feed him because he was no longer able to hold a spoon. Six months after Rituximab, his paraprotein was 0.9 g/L, and examination showed worsened tremor now also involving the jaw and the head, normal light touch sensation (improved), reduced pinprick sensation to the ankles bilaterally (improved) and significant improvement of walking and balance, no longer needing a walking stick. Rash-built Overall Disability Scale (R-ODS) was 17/48 while MRC sum score was 63/70 (improved). Brain MRI was normal, and NCS unchanged. One year after rituximab, his paraprotein concentration was 1.05 g/L, and his sensory symptoms, weakness, walking and balance had further improved while the tremor was subjectively slightly worsened. R-ODS was now 22/48 while MRC sum score was 66/70. IVIg was initiated but discontinued without benefit after only 20 g of a planned 160 g because of severe headache, worsening tremor, and shivers. Tremor did not respond to propranolol (240 mg/day), or primidone (250 mg/day).

Cognitive reserve theory seeks to explain the observed mismatch between the degree of brain pathology and clinical manifestations. Early‐life education, midlife social and occupational activities and later‐life cognitive and social interactions are associated with a more favourable cognitive trajectory in older people. Previous studies of Parkinson's disease (PD) have suggested a possible role for the effects of cognitive reserve, but further research into different proxies for cognitive reserve and longitudinal studies is required. This study examined the effects of cognitive lifestyle on cross‐sectional and longitudinal measures of cognition and dementia severity in people with PD.

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Background Depression and anxiety in Parkinson's disease are common and frequently co-morbid, with significant impact on health outcome. Nevertheless, management is complex and often suboptimal. The existence of clinical subtypes would support stratified approaches in both research and treatment.Method Five hundred and thirteen patients with Parkinson's disease were assessed annually for up to 4 years. Latent transition analysis (LTA) was used to identify classes that may conform to clinically meaningful subgroups, transitions between those classes over time, and baseline clinical and demographic features that predict common trajectories.Results In total, 64.1% of the sample remained in the study at year 4. LTA identified four classes, a Psychologically healthy' class (approximately 50%), and three classes associated with psychological distress: one with moderate anxiety alone (approximately 20%), and two with moderate levels of depression plus moderate or severe anxiety. Class membership tended to be stable across years, with only about 15% of individuals transitioning between the healthy class and one of the distress classes. Stable distress was predicted by higher baseline depression and psychiatric history and younger age of onset of Parkinson's disease. Those with younger age of onset were also more likely to become distressed over the course of the study.Conclusions Psychopathology was characterized by relatively stable anxiety or anxious-depression over the 4-year period. Anxiety, with or without depression, appears to be the prominent psychopathological phenotype in Parkinson's disease suggesting a pressing need to understanding its mechanisms and improve management.

ObjectivesHolding positive beliefs about illness and having an optimistic outlook have been associated with increased well-being across a range of health conditions. However, research has indicated that being very optimistic may not actually be beneficial, and holding a realistic attitude is more adaptive in some forms of chronic illness, for example, Parkinson's disease (PD). This study aimed to explore the nature of relationships between illness perceptions, optimism and well-being: specifically, whether a linear or non-linear relationship best described the data. Additionally, the proposed moderating effect of optimism on the relationship between illness perceptions and well-being was tested.DesignA total of 109 participants with idiopathic PD completed questionnaire measures of illness perception, optimism, mood and health-related quality of life (HRQoL).MethodsMultiple regression analyses were used to explore relationships between illness perceptions, optimism, mood and HRQoL. The potential curvilinear effects of illness perceptions and optimism were modelled using squared variables and linear and quadratic curve estimation.ResultsHolding positive illness perceptions predicted better well-being. Some evidence for a non-linear relationship between optimism and mood was found. Optimism had a significant moderating effect on the relationship between specific illness perceptions and outcome.ConclusionsOptimism appears to provide protection against some negative perceptions of illness and was associated with better mood and HRQoL. The findings indicate that specific illness perceptions may be beneficial targets for therapy. Therapeutic interventions should focus on enhancing positive perceptions of PD but potentially more importantly general optimistic attitude to maximize well-being.Statement of contributionWhat is already known on this subject? Positive illness perceptions and high optimism are associated with better well-being in a range of conditions, both chronic and acute. Preliminary studies suggest that in chronic degenerative diseases, marked positive optimism confers no additional benefit over medium levels of optimism for well-being and is associated with less use of adaptive coping.What does this study add?Optimism moderates the effects of specific negative illness perceptions on well-being in Parkinson's disease.No evidence was found that unrealistic positive illness perceptions are detrimental to well-being.Adaptive illness perceptions may be condition specific.