title: Characterizing motor and non-motor aspects of early-morning off periods in Parkinson's disease: an international multicenter study.
abstract: BACKGROUND
  The characteristic off periods that develop over time in subjects with Parkinson's disease (PD) on chronic levodopa therapy are usually considered to be motor complications but more recently the important contribution of non-motor off and non-motor fluctuations has also been acknowledged. Early-morning off (EMO) periods in PD patients are known to be a cause of significant disability, in addition to having a negative impact on quality of life. Yet EMOs are poorly defined, particularly in relation to non-motor symptoms (NMS).
  
  
  METHODS
  This European, multicentre, observational study was undertaken to characterize the range and patterns of NMS that occur during EMO periods in a consecutive series of PD patients.
  
  
  RESULTS
  The results demonstrate that EMO periods are common and occur in 59.7% of subjects across all disease stages in line with other reports. However, importantly, in 88.0% of those, EMOs were found to be associated with NMS. The predominant NMS associated with EMO were urinary urgency, anxiety, dribbling of saliva, pain, low mood, limb paresthesia and dizziness. The patterns of dopaminergic treatment being taken by patients in this study suggested that a prolonged-release or continuous drug delivery strategy can alleviate some NMS associated with EMO.
  
  
  CONCLUSIONS
  In light of these findings it is suggested that greater awareness, recognition and appropriate treatment of EMO and NMS could improve the overall 24-h management of PD. An EMO-specific scale/questionnaire which captures both motor and NMS associated with EMO over the off time period is warranted.
authors.affiliation: King's College Hospital, London, UK. Electronic address: a.rizos@nhs.net.
authors.forename: A
authors.initials: A
authors.lastname: Rizos
authors.affiliation: Carlos III Institute of Health, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martinez-Martin
authors.affiliation: Klinikum Reinkenheide, Bremerhaven, Germany; University Hospital, Lund, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Odin
authors.affiliation: RCCS San Camillo Venice and University of Padua, Venice, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Antonini
authors.affiliation: Princess Royal University Hospital, Orpington, UK.
authors.forename: B
authors.initials: B
authors.lastname: Kessel
authors.affiliation: King's College Hospital, London, UK.
authors.forename: T Klemencic
authors.initials: TK
authors.lastname: Kozul
authors.affiliation: King's College Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Todorova
authors.affiliation: Primary Care and Public Health Sciences, King's College London, London, UK; NIHR cBRC, Guy's and St Thomas' NHS Trust and King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Douiri
authors.affiliation: King's College Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.affiliation: IRCCS San Raffaele, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Stocchi
authors.affiliation: Oslo University Hospital and University of Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Dietrichs
authors.affiliation: King's College Hospital, London, UK; University Hospital Lewisham, London, UK.
authors.forename: K Ray
authors.initials: KR
authors.lastname: Chaudhuri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D011788:Quality of Life; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D007980:Levodopa
keywords: Early-morning off periods; Non-motor; Parkinson's disease; Parkinsonism