Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

Automated spike and seizure detection: Are we ready for implementation?

OBJECTIVE: Automated detection of spikes and seizures has been a subject of research for several decades now. There have been important advances, yet automated detection in EMU (Epilepsy Monitoring Unit) settings has not been accepted as standard practice. We intend to implement this software at our EMU and so carried out a qualitative study to identify factors that hinder ('barriers') and facilitate ('enablers') implementation. METHOD: Twenty-two semi-structured interviews were conducted with 14 technicians and neurologists involved in recording and reporting EEGs and eight neurologists who receive EEG reports in the outpatient department. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ). RESULTS: We identified 14 barriers and 14 enablers for future implementation. Most barriers were reported by technicians. The most prominent barrier was lack of trust in the software, especially regarding seizure detection and false positive results. Additionally, technicians feared losing their EEG review skills or their jobs. Most commonly reported enablers included potential efficiency in the EEG workflow, the opportunity for quantification of EEG findings and the willingness to try the software. CONCLUSIONS: This study provides insight into the perspectives of users and offers recommendations for implementing automated spike and seizure detection in EMUs.

Automated seizure detection in an EMU setting: Are software packages ready for implementation?

PURPOSE: We assessed whether automated detection software, combined with live observation, enabled reliable seizure detection using three commercial software packages: Persyst, Encevis and BESA. METHODS: Two hundred and eighty-six prolonged EEG records of individuals aged 16-86 years, collected between August 2019 and January 2020, were retrospectively processed using all three packages. The reference standard included all seizures mentioned in the clinical report supplemented with true detections made by the software and not previously detected by clinical physiologists. Sensitivity was measured for offline review by clinical physiologists and software seizure detection, both in combination with live monitoring in an EMU setting, for all three software packages at record and seizure level. RESULTS: The database contained 249 seizures in 64 records. The sensitivity of seizure detection was 98% for Encevis and Persyst, and 95% for BESA, when a positive results was defined as detection at least one of the seizures occurring within an individual record. When positivity was defined as recognition of all seizures, sensitivity was 93% for Persyst, 88% for Encevis and 84% for BESA. Clinical physiologists' review had a sensitivity of 100% at record level and 98% at seizure level. The median false positive rate per record was 1.7 for Persyst, 2.4 for BESA and 5.5 for Encevis per 24 h. CONCLUSION: Automated seizure detection software does not perform as well as technicians do. However, it can be used in an EMU setting when the user is aware of its weaknesses. This assessment gives future users helpful insight into these strengths and weaknesses. The Persyst software performs best.

Automated spike detection: Which software package?

PURPOSE: We assessed three commercial automated spike detection software packages (Persyst, Encevis and BESA) to see which had the best performance. METHODS: Thirty prolonged EEG records from people aged at least 16 years were collected and 30-minute representative epochs were selected. Interictal epileptiform discharges (IEDs) were marked by three human experts and by all three software packages. For each 30-minutes selection and for each 10-second epoch we measured whether or not IEDs had occurred. We defined the gold standard as the combined detections of the experts. Kappa scores, sensitivity and specificity were estimated for each software package. RESULTS: Sensitivity for Persyst in the default setting was 95% for 30-minute selections and 82% for 10-second epochs. Sensitivity for Encevis was 86% (30-minute selections) and 61% (10-second epochs). The specificity for both packages was 88% for 30-minute selections and 96%-99% for the 10-second epochs. Interrater agreement between Persyst and Encevis and the experts was similar than between experts (0.67-0.83 versus 0.63-0.67). Sensitivity for BESA was 40% and specificity 100%. Interrater agreement (0.25) was low. CONCLUSIONS: IED detection by the Persyst automated software is better than the Encevis and BESA packages, and similar to human review, when reviewing 30-minute selections and 10-second epochs. This findings may help prospective users choose a software package.

Factors facilitating and hindering the implementation of the European Society of Cardiology Syncope Guidelines at the Emergency Department: A nationwide qualitative study.

AIMS: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation. METHODS AND RESULTS: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice. CONCLUSION: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.

[Long-term follow-up of psychogenic pseudosyncope]. / Het beloop van psychogene pseudosyncope na meedelen van de diagnose.

BACKGROUND: Patients with psychogenic pseudosyncope (PPS) are frequently seen by neurologists and psychiatrists. As of yet, there has been no follow-up study of patients with PPS after communicating the diagnosis. AIM: To determine the outcome of patients with psychogenic pseudosyncope (PPS) after communicatingthe diagnosis. METHOD: A retrospective cohort study of patients with PPS referred to a tertiary referral center for syncope from 2007 to 2015. We reviewed patient records, studying attack frequency, factors possibly affecting attack frequency, health care use and quality of life using questionnaires. We explored influences on absence of attack and attack frequency in the six months before follow-up for age, sex, level of education, duration until a diagnosis was made, probability of diagnosis, additional syncope and acceptance of diagnosis. RESULTS: 47 out 57 PPS cases could be traced, of these 35 (74%) participated. Twelve (34%) were attack free for at least six months. The median time from diagnosis to follow-up was 50 months (range 6-103 months). Communication and explanation of the diagnosis resulted in immediate reduction of attack frequency (p=0.007) from the month before diagnosis (median one attack, range 0-156) to the month afterwards (median one attack, range 0-16). In the six months before follow-up the number of admissions decreased from 19/35 to 0/35 (p = 0.002). Furthermore, the demand for somatic health care shifted to psychiatric care (p < 0.0001). Quality of life at follow-up (Short Form Health Survey 36; SF-36) showed lower scores for seven of the eight domains compared to matched Dutch control values. The quality of life was not significantly influenced by absence of attack. CONCLUSION: After communicating the diagnosis of PPS, attack frequency decreased and health care use shifted toward mental care. Low quality of life underlines the fact that PPS is a serious condition. Improvement of quality of life probably requires both a longer treatment and longer follow-up.

[Driving status of syncope patients is not part of standard advice]. / Rijgeschiktheid bij syncope niet standaard besproken.

OBJECTIVE: Some medical problems, such as syncope, have direct consequences for fitness to drive. Our objective was to discover if patients had been informed about their driving status after a syncopal episode by their physician, and if this advice was in line with current legislation. DESIGN: Cross-sectional study. METHOD: By means of a structured questionnaire, 150 patients referred to the syncope clinic at the Academic Medical Centre, Amsterdam, were asked about the advice they had received concerning their driving status during previous consultations with their general practitioner or specialists. A syncope expert then assessed the driving status of all patients in the light of the existing and new ruling. RESULTS: In 121 of the 150 patients (81%), a certain or highly-likely cause for their loss of consciousness was determined: 68 patients had reflex syncope, 25 patients orthostatic hypotension, 20 patients psychogenic pseudosyncope, three patients cardiac syncope, three patients had epilepsy and two patients another diagnosis. Seven patients had experienced an episode while driving. Only 26/150 patients (17%) reported that the consequences of their episodes for their driving status had been discussed with them at earlier consultations. If driving was discussed, in only 31% had the current Dutch legislation on driving been followed. Over a third (38%) of the patients felt they should no longer drive. CONCLUSION: Fewer than one in five patients reported that driving status was discussed by a physician after a syncope episode. If advice had been given, it was often not in line with current legislation.

Prevalence and Prescribed Treatments of Orthostatic Hypotension in Institutionalized Patients with Parkinson's Disease.

BACKGROUND: Orthostatic hypotension (OH) in Parkinson's disease (PD) is a common non-motor sign that can be hard to recognize and treat. OH prevalence and treatment in institutionalized PD-patients remains unknown. OBJECTIVE: The aim of this study was to explore the prevalence and prescribed treatments of OH in institutionalized patients with PD. METHOD: A cross-sectional study of nursing homes in the south-east of the Netherlands identified 64 residents with PD (inclusion criteria: MMSE >18). Assessments included blood pressure measurement, both supine and in the upright position (after 1 minute and after 3 minutes of standing), and 2 questions on cardiovascular items including falls of the validated Non-Motor Symptom Scale (NMSS). OH was defined according to the consensus guidelines. OH was considered as 'probably symptomatic' if patients had a concomitant frequency score >1 on the selected NMSS items, and 'probably asymptomatic' for a frequency score of 0. If OH was not present, but patients had a frequency score >1, OH was considered as 'possibly symptomatic'. RESULTS: The prevalence of OH was 51.6%, almost equally divided into probably symptomatic and probably asymptomatic cases. Another 20.6% had possibly symptomatic OH. Importantly, only two patients with symptomatic OH had an OH diagnosis noted in their medical records. Five received domperidone, one received fludrocortison and none received midodrine. CONCLUSION: One half of institutionalized PD patients had OH, of whom half were probably symptomatic. OH was rarely noted in the medical records, suggesting underdiagnosis. Finally, OH was rarely treated, suggesting undertreatment.

Tilt table testing in neurology and clinical neurophysiology.

Reflex syncope is responsible for 1-6% of hospital admissions and the economic burden of syncope is huge. A considerable part of these high costs is still spent on tests that are not indicated. Till now few neurologists have taken an interest in syncope and tilt table testing (TTT). However, reflex syncope and epilepsy are often in each other's differential diagnosis and require a similar emphasis on history taking and deductive reasoning. A TTT can be helpful for diagnosis and treatment. The pathophysiological rationale behind the TTT is the fact that it uses gravity to provoke a downwards shift of blood that in turn triggers syncope. Various indications and methods of the TTT are discussed in this paper.

Effect of orthostatic hypotension on sustained attention in patients with autonomic failure.

INTRODUCTION: Orthostatic hypotension has been associated with impaired cognitive function, but cognitive function during orthostatic hypotension has hardly been studied. We studied the effect of orthostatic hypotension, induced by head-up tilt (HUT), on sustained attention in patients with autonomic failure. METHODS: We studied the sustained attention to response task (SART) in the supine position and during HUT in 10 patients with autonomic failure and 10 age-matched and sex-matched controls. To avoid syncope, the tilting angle was tailored to patients to reach a stable systolic blood pressure below 100 mm Hg. Controls were all tilted at an angle of 60°. Cerebral blood flow velocity, blood pressure and heart rate were measured continuously. RESULTS: In patients, systolic blood pressure was 61.4 mm Hg lower during HUT than in the supine position (p<0.001). Patients did not make more SART errors during HUT than in the supine position (-1.3 errors, p=0.3). Controls made 2.3 fewer errors during SART in the HUT position compared to the supine position (p=0.020). SART performance led to an increase in systolic blood pressure (+11.8 mm Hg, p=0.018) and diastolic blood pressure (+5.8 mm Hg, p=0.017) during SART in the HUT position, as well as to a trend towards increased cerebral blood flow velocity (+3.8 m/s, p=0.101). DISCUSSION: Orthostatic hypotension in patients with autonomic failure was not associated with impaired sustained attention. This might partly be explained by the observation that SART performance led to a blood pressure increase. Moreover, the upright position was associated with better performance in controls and, to a lesser extent, also in patients.

[Unexplained loss of consciousness: the diagnosis is never based on one symptom]. / Onverklaarde wegrakingen: de diagnose berust nooit op één symptoom.

Patients with transient loss of consciousness are often seen by a variety of specialists. Even if typical signs occur, it can be difficult to identify specific causes. We discuss two patients with complex presentations. The first patient was diagnosed with sleep syncope, a relatively unknown type of reflex syncope. The prodromal symptoms of discomfort and the subsequent loss of consciousness occurred while the patient was in bed or got up to go to the toilet due to abdominal symptoms. The onset in supine position was misleading, since this is a well-known alarm symptom of a possible cardiac cause. The second patient had vasovagal syncope followed by a psychogenic pseudosyncope. This resulted in frequent loss of consciousness of long duration with typical and atypical triggers and uncommon syncopal signs, including eye closure. These conflicting symptoms can be a pitfall and clinical expertise is required to identify the type of syncope.

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

OBJECTIVES: Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps. METHODS: Nine brachial plexus patients with insufficient elbow flexion (i.e., partial denervation) received intramuscular escalating doses of autologous bone marrow-derived mononuclear cells, combined with tendon transfers. Effect parameters included biceps biopsies, motor unit analysis on needle electromyography and computerised muscle tomography, before and after cell therapy. RESULTS: No adverse effects in vital signs, bone marrow aspiration sites, injection sites, or surgical wound were seen. After cell therapy there was a 52% decrease in muscle fibrosis (p = 0.01), an 80% increase in myofibre diameter (p = 0.007), a 50% increase in satellite cells (p = 0.045) and an 83% increase in capillary-to-myofibre ratio (p < 0.001) was shown. CT analysis demonstrated a 48% decrease in mean muscle density (p = 0.009). Motor unit analysis showed a mean increase of 36% in motor unit amplitude (p = 0.045), 22% increase in duration (p = 0.005) and 29% increase in number of phases (p = 0.002). CONCLUSIONS: Mononuclear cell injection in partly denervated muscle of brachial plexus patients is safe. The results suggest enhanced muscle reinnervation and regeneration. Cite this article: Bone Joint Res 2014;3:38-47.

Carotid body tumors are not associated with an increased risk for sleep-disordered breathing.

PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.

At the heart of the arterial baroreflex: a physiological basis for a new classification of carotid sinus hypersensitivity.

The aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well-established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnose CSH are too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitory CSH (asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients with CSH should be thought of as being 'mixed', between cardioinhibition and vasodepression. The proposed stricter set of criteria for CSH should be evaluated in future studies.

Deficient sustained attention to response task and P300 characteristics in early Huntington's disease.

Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington's disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (p < 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (p < 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group.

Basal ganglia volume is strongly related to P3 event-related potential in premanifest Huntington's disease.

BACKGROUND: The P3 event-related potential (ERP) is presumably partly generated by the basal ganglia. Because degeneration of these brain structures starts many years before clinical disease onset in Huntington's disease (HD), studying the interplay between P3 characteristics and basal ganglia volumes in 'premanifest' carriers might lead to new insights into the disease process. METHODS: Fourteen premanifest\ HD mutation carriers and twelve non-mutation carriers underwent clinical, MRI and P3-ERP investigations. The P3 was measured during the Sustained Attention to Response Task. RESULTS: P3 amplitude and latency did not differ between groups. In carriers, longer P3 latency during Go-trials was strongly associated with smaller caudate, putamen and globus pallidus volumes (r values up to -0.827, P ≤ 0.001). CONCLUSION: The exceptionally strong relations of P3 latency with basal ganglia volumes in carriers suggest that the P3 may provide a marker for disease progression in HD.

Disturbed subjective sleep characteristics in adult patients with long-standing type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Decreased sleep duration and/or impaired sleep quality negatively influence glucoregulation. The aim of this study was to assess subjective sleep characteristics in patients with type 1 diabetes, to relate sleep characteristics to long-term glycaemic control and to assess possible risk factors for impaired sleep. METHODS: We studied 99 adult patients with type 1 diabetes (55 men, 44 women, duration of diabetes 26.9 ± 1.2 years) and 99 age-, sex- and BMI-matched non-diabetic controls. Subjective sleep characteristics were assessed by validated questionnaires, i.e. Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and the Berlin Questionnaire. Glucoregulation was assessed by HbA(1c) values. Clinical variables were obtained from medical charts. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS). Peripheral polyneuropathy was assessed by neurological examination and quantitative sensory testing. RESULTS: Of the patients with type 1 diabetes, 35% had subjective poor sleep quality compared with 20% of the control participants (p = 0.021). A higher proportion of the patients with type 1 diabetes were at increased risk for obstructive sleep apnoea (OSA) (17.2% vs 5.1%, p = 0.012). There was no significant association between individual sleep characteristics and HbA(1c) values. On logistic regression analysis, the HADS depression score, presence of peripheral polyneuropathy, habitual snoring and other sleep disturbances (e.g. hypoglycaemia) were independently associated with poor sleep quality. CONCLUSIONS/INTERPRETATION: Adult patients with long-standing type 1 diabetes mellitus have disturbed subjective sleep quality and a higher risk for OSA compared with control participants. Subjective sleep disturbances are part of the complex syndrome of long-standing type 1 diabetes.

Patients previously treated for nonfunctioning pituitary macroadenomas have disturbed sleep characteristics, circadian movement rhythm, and subjective sleep quality.

CONTEXT AND OBJECTIVE: Fatigue and excessive sleepiness have been reported after treatment of nonfunctioning pituitary macroadenomas (NFMA). Because these complaints may be caused by disturbed nocturnal sleep, we evaluated objective sleep characteristics in patients treated for NFMA. DESIGN: We conducted a controlled cross-sectional study. SUBJECTS AND METHODS: We studied 17 patients (8 women; mean age, 54 yr) in remission of NFMA during long-term follow-up (8 yr; range, 1-18 yr) after surgery (n = 17) and additional radiotherapy (n = 5) without comorbidity except for hypopituitarism and 17 controls matched for age, gender, and body mass index. Sleep was assessed by nocturnal polysomnography, sleep and diurnal movement patterns by actigraphy, and quality of life and subjective sleep characteristics by questionnaires. RESULTS: Compared to controls, patients had reduced sleep efficiency, less rapid eye movement sleep, more N1 sleep, and more awakenings in the absence of excessive apnea or periodic limb movements. Actigraphy revealed a longer sleep duration and profound disturbances in diurnal movement patterns, with more awakenings at night and less activity during the day. Patients scored higher on fatigue and reported impaired quality of life. CONCLUSION: Patients previously treated for NFMA suffer from decreased subjective sleep quality, disturbed distribution of sleep stages, and disturbed circadian movement rhythm. These observations indicate that altered sleep characteristics may be a factor contributing to impaired quality of life and increased fatigue in patients treated for NFMA.

Autonomic symptoms in patients and pre-manifest mutation carriers of Huntington's disease.

BACKGROUND AND PURPOSE: Although autonomic function tests have revealed abnormalities of the autonomic nervous system in Huntington's disease (HD), autonomic symptoms and their association with other symptoms and signs of HD have not yet been assessed in large groups of patients or pre-manifest mutation carriers. Therefore, we aimed at delineating the characteristics and correlates of autonomic symptoms in HD. METHODS: Using the scales for outcomes in Parkinson's disease-autonomic symptoms (SCOPA-AUT) and Beck Depression Inventory questionnaires, autonomic symptoms and depressed mood were assessed in 63 patients with HD, 21 pre-manifest mutation carriers, and 85 controls. The Unified Huntington's Disease Rating Scale was used to assess other HD symptoms and signs. RESULTS: Relative to controls, patients with HD experienced significantly more gastrointestinal, urinary, cardiovascular and, in men, sexual problems. The most prevalent symptoms were swallowing difficulties, erection and ejaculation problems, dysphagia, sialorrhea, early abdominal fullness, straining for defecation, fecal and urinary incontinence, urgency, incomplete bladder emptying, and light-headedness whilst standing. Pre-manifest mutation carriers experienced significantly more swallowing difficulties and light-headedness on standing up compared with controls. In patients with HD, autonomic symptoms were associated with a greater degree of functional disability, more severe depression, and antidepressant drugs use. However, depression was the only independent predictor of autonomic dysfunction. CONCLUSIONS: Autonomic symptoms are highly prevalent in patients with HD and may even precede the onset of motor signs. Moreover, autonomic dysfunction is related to functional disability and depression in HD.