Alessandra Fanciulli

EFNS/MDS‐ES recommendations for the diagnosis of Parkinson's disease

A Task Force was convened by the EFNS/MDS‐ES Scientist Panel on Parkinsons disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD.

New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study

Objectives Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA), a fatal progressive neurodegenerative disorder associated with autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the clinical spectrum of OH in a large European cohort of patients with MSA and (2) to investigate whether a prolonged postural challenge increases the sensitivity to detect OH in MSA. Methods Assessment of OH during a 10u2005min orthostatic test in 349 patients with MSA from seven centres of the European MSA-Study Group (age: 63.6±8.8u2005years; disease duration: 4.2±2.6u2005years). Assessment of a possible relationship between OH and MSA subtype (P with predominant parkinsonism or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS) scores and drug intake. Results 187 patients (54%) had moderate (>20u2005mmu2005Hg (systolic blood pressure (SBP)) and/or >10u2005mmu2005Hg (diastolic blood pressure (DBP)) or severe OH (>30u2005mmu2005Hg (SBP) and/or >15u2005mmu2005Hg (DBP)) within 3u2005min and 250 patients (72%) within 10u2005min. OH magnitude was significantly associated with disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and supine hypertension. OH severity was not associated with MSA subtype. Drug intake did not differ according to OH magnitude except for antihypertensive drugs being less frequently, and antihypotensive drugs more frequently, prescribed in severe OH. Conclusions This is the largest study of OH in patients with MSA. Our data suggest that the sensitivity to pick up OH increases substantially by a prolonged 10u2005min orthostatic challenge. These results will help to improve OH management and the design of future clinical trials.

Autonomic function testing in Friedreich’s ataxia

BackgroundFriedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking.MethodsGenetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed.Results20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 agedu2009>u200950).ConclusionsFRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function.

Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS): Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH)

PurposePatients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright position owing to impaired autonomic regulation. A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure.MethodsAs a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed. Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017. Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here. The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension.ResultsIn patients with neurogenic orthostatic hypotension, nSH is defined as systolic BPu2009≥u2009140xa0mmHg and/or diastolic BPu2009≥u200990xa0mmHg, measured after at least 5xa0min of rest in the supine position. Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytimexa0BP values. Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management.ConclusionsThe establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.

Very late-onset pure autonomic failure

to result in a deficiency of mature PDGF-BB. Although the clinical episodes exhibited by our patients resembled MR-1-associated PNKD, they showed several atypical features: MR-1-associated PNKD attacks are frequently triggered by alcohol, coffee, tea, fatigue, or stress, whereas our patients reported no clear precipitants; MR-1associated PNKD attacks usually last from several minutes to hours, whereas the attacks observed in our patients lasted for a much shorter period ( 1 minute). Etiologically, PNKD could be primary or secondary to an identifiable cause, such as multiple sclerosis, stroke, trauma, and metabolic disorders. Notably, coexistence of PNKD and brain calcification in a 23-year-old man has been reported in the literature, in which similar clinical episodes were described. Because the PNKD phenotype cosegregated with brain calcification in this family, and no mutation was found in the MR-1 gene, we speculate that the PNKD symptoms exhibited by our patients might be secondary to brain calcification. While the manuscript was under revision, another study has reported the c.232C>T PDGFB mutation in a sporadic PFBC patient with memory impairment and headache. It is notable that the clinical feature of our patients is different from that shown in the sporadic case. This might be related with their genetic background differences.

Practical Instructions for the 2018 ESC Guidelines for the diagnosis and management of syncope

The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oxfordjournals.org).

Autonomic function testing in spinocerebellar ataxia type 2

PurposeTo assess whether autonomic failure belongs to the clinical spectrum of spinocerebellar ataxia type 2 (SCA2), an autosomal dominant genetic disorder showing progressive cerebellar and brainstem dysfunction.MethodsWe evaluated cardiovascular autonomic function in 8 patients with SCA2 and 16 age- and gender-matched healthy controls. Other autonomic domains were examined through standardized questionnaires and by testing the skin sympathetic reflex.ResultsPatients with SCA2 showed normal responses to cardiovascular autonomic function tests, with the exception of lower baroreflex sensitivity upon standing compared to controls. In questionnaires, 7 out of 8 patients reported bladder disturbances, while 3 out of 6 tested patients had no skin sympathetic reflex.ConclusionsWe did not observe clinically overt cardiovascular autonomic failure in patients with SCA2. Other autonomic domains (i.e., bladder and sudomotor function) may be affected in the disease.

Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms

Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced hypotension are common features of cardiovascular autonomic failure. Despite the serious impact on patient’s quality of life, evidence-based guidelines for non-pharmacological and pharmacological management are lacking at present. Here, we provide a systematic review of the literature on therapeutic options for neurogenic orthostatic hypotension and related symptoms with evidence-based recommendations according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Patient’s education and non-pharmacological measures remain essential, with strong recommendation for use of abdominal binders. Based on quality of evidence and safety issues, midodrine and droxidopa reach a strong recommendation level for pharmacological treatment of neurogenic orthostatic hypotension. In selected cases, a range of alternative agents can be considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation strength is weak and quality of evidence is low (atomoxetine, octreotide) or very low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin). In case of severe postprandial hypotension, acarbose and octreotide are recommended (strong recommendation, moderate level of evidence). Alternatively, voglibose or caffeine, for which a weak recommendation is available, may be useful.

Bladder and Sexual Dysfunction

Urinary function consists of a “storage” phase, in which tonic activation of urethral sphincter muscle occurs and bladder detrusor muscle is inhibited, and a “voiding” phase, in which detrusor activation and sphincter relaxation favor passing of urine. Both are under voluntary and involuntary neural control. Disorders of neural control of urinary function are also known as “neurogenic bladder” or “neurogenic lower urinary tract dysfunction.” Four main clinical pathological patterns can be distinguished at examination, with different therapeutic implications [27]: n n1. n nBladder detrusor overactivity: bladder storage capacity is reduced, but no or only low urine post-void volume occurs. n n n n n2. n nDetrusor sphincter dyssynergia: bladder storage capacity is reduced. Lack of coordination between bladder detrusor activation and urethral sphincter relaxation additionally induces post-void residual urine. n n n n n3. n nHypoactive bladder: bladder capacity is increased. Insufficient detrusor activation leads to high post-void residual urine. n n n n n4. n nHypoactive sphincter: bladder storage capacity is reduced, with no post-void residual urine.

Autonomic History Taking and Key Symptoms: Where Is the Autonomic Disease?

The autonomic nervous system controls the cardiovascular, gastrointestinal, urogenital, respiratory, thermoregulatory, and pupillary function and regulates sleep. Such a wide distribution is reflected by the protean manifestations of autonomic disorders, which range from generalized failure to isolated organ dysfunction, thus mimicking, among others, primary disorders of the innervated organs.