Parkinsons disaese

The stages Roberto Rico

History  

•  1817    James  Parkinson  

•  1867    Jean-­‐Mar6n  Charcot  •  Bradykinesia  •  Dysautonomia  

•  Pain  

•  1990    Disease  modifying  efforts  

     

Symptoms  of  Parkinson’s  Disease1-­‐5  

Motor symptoms Nonmotor symptoms • Tremor at rest

• Bradykinesia

• Rigidity

• Postural instability

• Other (eg, dysarthria, shuffling gate, dystonia)

• Neuropsychiatric (eg, dementia, cognitive decline, depression, anxiety, psychosis, apathy)

• Sensory (eg, hyposmia, pain, paresthesias)

• Sleep disturbances (eg, RBD, RLS, sleep apnea, sleep attacks, daytime somnolence, insomnia)

• Autonomic dysfunction

• Other (eg, fatigue, weight loss)

RBD  =  rapid  eye  movement  behavior  disorder;  RLS  =  restless  legs  syndrome.  1.  Berg.  Neurodegener  Dis.  2008;5:133-­‐136.  2.  Jankovic.  J  Neurol  Neurosurg  Psychiatry.  2008;79:368-­‐376.  3.  Thanvi  et  al.  Postgrad  Med  J.  2003;79:561-­‐565.  4.  Weintraub  et  al.  Am  J  Manag  Care.  2008;14:S40-­‐S48.  5.  Zesiewicz  et  al.  Expert  Rev  Neurother.  2006;6:1811-­‐1822.  

Clinical  Diagnosis  

•  Tremor  •  Rigidity  •  Bradykinesia  

•  Suppor6ng  features  –  Assymetric  symptoms  

–  Other  parkinsonism  

Early  diagnos6cs  

•  Focus on non-motor symptoms

•  Biomarker development

•  Genetic contribution (Genome wide association)

•  Disaese modifying treatments

Neuro  imaging  in  PD  

PD  Pathology  

•  Alpha-­‐synuclein  

•  Widely  described  in  other  6ssues  

•  Outside  the  nervous  system  •  Autonomic  nerves  heart,gut,prstate  

•  Skin  6ssue  

Pathology  in  M.Parkinson  

Parkinson  Associated  Risk  Syndrome  

•  PARS  

•  Prephysiological  •  Preclinical  •  Premotor  

•  prediagnos6c  

Early  Nonmotor  Signs  of  PD  

•  Probable  early  signs  – Cons6pa6on  – Olfactory  deficit  – REM  sleep  behavior  disorder  – Depression  

•  Possible  early  signs  – Apathy  – Fa6gue  – Anxiety  

PD,  Parkinson’s  disease;  REM,  rapid  eye  movement.  Chaudhuri  et  al.  Lancet  Neurol.  2006;5(3):235-­‐245.  

Cardinal  signs  

•  Res6ng  tremor  

•  Bradykinesia  

•  Rigidity  

•  Postural  instability  

Nonmotor  Features  of  PD  

Psychiatric disorders1

•  Depression in up to 40% of patients •  Anxiety in ~30% of patients •  Psychosis •  Behavioural disorders

Cognitive disorders1,2 •  Mild cognitive impairment •  Dementia in 15% to 40% of patients

Sleep abnormalities1,3 •  >70% of patients •  REM sleep behavior disorder

Autonomic dysfunction1-3

•  Constipation •  Orthostatic hypotension •  Urinary & Sexual Dysfunction

Sensory3 •  Olfactory dysfunction

Miscellaneous1,2 •  Fatigue and weight loss •  Pain

PD,  Parkinson’s  disease;  REM,  rapid  eye  movement.  1.  Thanvi  et  al.  Postgrad  Med  J.  2003;79(936):561-­‐565.  2.  Fahn  and  Sulzer.  NeuroRx.  2004;1(1):139-­‐154.  3.  Jankovic.  J  Neurol  Neurosurg  Psychiatry.  2008;79(4):368-­‐376.  

Non-­‐motor  

•  Depression  •  Anxiety  •  Psychosis  •  Demen6a  

•  Sleep  disfunc6on  •  Behavioral  disorders  

Non-­‐motor  

•  Autonomic  dysfunc6on  •  Cardiovascular  dysfunc6on  •  Gastro  intes6nal  symptoms  

•  Urinary  and  sexual  dysfunc6on  •  Hyperhydrosis  •  Hyposmia  

•  Pain  •  Visual  disturbances  

Future  perspec6ve  for  non  motor  signs  

•  Underrecognizedand  undertreated  

•  Important  source  of  disability  

•  Early  diagnosis  and  disaese  modifying  treatments  

•  Not  only  dopaminergic  

conclusions •  Non-­‐motor  symptoms  are  ofen  an  integral  part  of  the  disaese  

•  Non  motor  symptoms  worsen  quality  of  life  for  PD  pa6ents  

•  Early  diagnosis  is  aimed  at  disaese  modifying  treatments