DIAGNOSIS _ TREATMENT OF PARKINSON'S DISEASE

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DIAGNOSIS _ TREATMENT OF PARKINSON'S DISEASE Powered By Docstoc
					DIAGNOSIS & TREATMENT
OF PARKINSON’S DISEASE

          May 7, 2008
        Sadhana Prasad

   Symposium on Changes and
   Challenges in Geriatric Care
             Disclosures
• Work with various pharmaceutical
  companies intermittently
• Honorarium will be donated
              OBJECTIVES


1. Illustrate medications and
 conditions that may mimic PD
2. Describe the early symptoms of Parkinson’s
  Disease (PD)
3. Discuss initiating and stopping medications
        Parkinson’s Disease
Characterized by: (Slow,Stiff,Shaky)
• Bradykinesia *
• Rigidity *
• Rest tremor--3-6Hz pill-rolling (absent 1/3)
• Postural instability
      Parkinson’s Disease (PD)
• First description 1817
  Parkinson, James An Essay on the Shaking Palsy, Sherwood, Neely, and Jones,
 London

• Progressive neurodegenerative disease
• Affects ages 40 onwards, mean age at
  diagnosis 70.5
• Complex disorder with motor, non-motor,
  neuropsychiatric features
       Disease vs Syndrome
• Disease = a morbid process having
  characteristic symptoms; pathology,
  etiology, and prognosis may be known

• Syndrome = a set of symptoms occurring
  together; different etiologies but similar
  presentation
     Parkinson’s Syndromes
Metabolic causes--
• Hypothyroidism
• Hypoparathyroidism
• Alcohol withdrawl (pseudoparkinsonism)
• Chronic liver failure
• Wilson’s disease
              P. Syndromes
Medications**/chemicals—
• neuroleptics (typicals more than the atypicals),
• SSRI (selective serotonin reuptake inhibitors),
• metoclopromide/maxeran,
• Reserpine,
• MPTP,
• in Methcathinone (ephedrone) users – high
  plasma Manganese levels (NEJM Mar 6, 2008)
• CO, cyanide, organic solvents, carbon disulfide
           P. Syndromes
Structural Causes—
• Strokes
• Tumors
• Chronic subdurals
• NPH (Normal Pressure Hydrocephalus)
             P.Syndromes
Lewy Body spectrum of Diseases
   (DLB=Dementia with LB)---
---early onset visual (or other) hallucinations
---fluctuating cognitive abilities
---sleep disorders
---neuroleptic sensitivity, even to atypicals
             P. Syndromes
PSP (progressive supranuclear palsy)—or
   Steeles Richardson Olszewski Syndrome
---gaze abnormalities
---postural instability, early unexplained falls
---bulbar features—dysphonia, dysarthria,
   dysphagia
---rapidly progressive---median 6 yrs.
            P. Syndromes
CBD (cortico basal degeneration)---
---Asymmetric parkinsonism
---postural instability
---ideomotor apraxia
---aphasia
---alien limb phenomenon
---impaired cortical sensations
            P. Syndromes
Multi System Atrophy-- (alpha-synuclein +
  glial cytoplasmic inclusions, autonomic
  dysfunction, pyramidal signs)
• Shy Drager Syndrome,
• Olivopontocerebellar atrophy,
• Striatonigral degeneration
           P. Syndromes
Other Neurodegenerative Disorders—
• Alzheimer’s Disease, later stages**
• Huntington’s Disease (rigid form)
• Frontotemporal Dementia with
  Parkinsonism, Chromosome-17 linked
  (FTDP-17)
• Spinocerebellar ataxias
            P. Syndromes
Infections---
• encephalitis
• HIV/AIDS
• Neurosyphilis
• Toxoplasmosis
• CJD (Creuzfeld Jakob)--prion disease
• Progressive multifocal
  leukoencephalopathy
              P. Syndrome
Essential Tremor---
---action tremor (not rest tremor)
---more rapid (greater than 3-6 Hz)
---usually hands, but can also affect legs,
   head/chin, voice, trunk
---can present with falls if legs and trunk
   involved
   P. Disease



??DIAGNOSIS??
           P. Dis -- Diagnosis


•   A clinical diagnosis
•   Cardinal features: Bradykinesia, rigidity
•   Trial of sinemet (Levodopa/carbidopa)
•   Confirmatory test: neuropathologic
    (autopsy)
       P. Disease-Diagnosis

• 1/3 will not respond to levodopa therapy
• 1/5 with P. Syndrome will respond to
  levodopa

---Follow- up with time needed to clarify
   diagnosis
      P. Disease---Diagnosis

Minimum therapeutic dose:
---300mg levodopa per day in divided doses
---can be lower in biologically old old
---vast majority will need 400-600mg
   levodopa daily to achieve significant
   benefit
      P. Disease- Diagnosis
Consider alternative diagnosis if:
• Early falls (postural instability)
• Poor response to levodopa
• Dysautonomia (urinary retention/atonic
  bladder, incontinence, orthostatic
  hypotension, impotence)
• No rest tremor (in 1/3)
       P. Disease-Diagnosis
Alternative Diagnosis cont’d…
• Cerebellar signs
• Positive Babinski
• Apraxia
• Gaze abnormailities
• Dementia concurrently with Parkinsonism
• Strokes
             P. Disease

INVESTIGATIONS:
• TSH
• Calcium, albumin
• CT head
              OBJECTIVES

1. Illustrate medications and conditions that may
  mimic PD

2. Describe the early
 symptoms of Parkinson’s
 Disease (PD)
3. Discuss initiating and stopping medications
               PD- CASE
• Mr AB, married, active farmer, stressed
  care-giver
• Drove his wife to the clinic, wife to see me
  re agitated dementia
• One son also attended
• Mr AB –stressed care-giver, on paxil
  (SSRI)
                 PD- case
Mr. AB--- stressed caregiver
• Slightly flexed posture
• Slightly bradykinetic
• Slightly diminished facial expression
• No difficulty turning, getting in/out of
  armless chair
              PD-case



―I don’t have Parkinson’s Disease!!‖
                PD- case
Mr. AB---
• 1 month later, referred re ? PD??
• CT head, TSH, Ca normal
• Slowing down x 1 yr, hypophonia, denied
  trouble turning in bed but took 5 tries in
  clinic, trouble getting out of soft chair,
  stopped taking baths x 3 years, mild rest
  tremor R hand, trouble doing up buttons
  and laces
                           IADL
              Instrumental Activities of Daily Living


•   S   shopping
•   H   housework
•   A   accounting
•   F   food preparation
•   T   transportation
                        ADL
                Activities of Daily Living

•   D   dressing
•   E   eating
•   A   ambulation
•   T   toiletting
•   H   hygiene
PD- case 1
        PD-case 1
clock
             PD –Case 1

Diagnosis:

Parkinson’s disease ---Hoehn & Yahr’s**
 stage 2
             Hoehn and Yahr scale

• 1. Unilateral involvement only, usually with minimal or
  no functional disability
• 2. Bilateral or midline involvement without impairment of
  balance
• 3. Bilateral disease; mild to moderate disability with
  impaired postural reflexes; physically independent
• 4. Severely disabling disease; still able to walk or stand
  unassisted
• 5. Confinement to bed or wheelchair unless aided
Hoehn, MM, Yahr, MD. Parkinsonism: onset, progression and mortality. Neurology 1967;
   17:427.
               PD- case 1
• MTO notified, ―not to cancel license‖
• Paxil *
• Sinemet regular 100/25 mg ½ tid, increase
  by ½ weekly till 1 tid
• Calcium and vitamin D3

• 2 months later, smiling, clock better,
  moving better, still flexed, no falls
        PD-case 1
clock
          PD—other issues
• Depression
• Dementia
• Driving
• Falls
• Neuropsychiatric features
• ―slowing down of thought processes‖ (the
  clock in Mr AB)
• Constipation
PD-Treatment



   ????
             OBJECTIVES

1. Illustrate medications and conditions that
  may mimic PD
2. Describe the early symptoms of
  Parkinson’s Disease (PD)

3. Discuss initiating and
 stopping medications
                       PD--Treatment
• Geared towards mobility—levodopa, dopamine
  agonists, MAO B inhibitors
• Rest tremor, cosmetic—anticholinergics (may
  worsen cognition)
• Postural imbalance—no pharmacological
  treatment; exercise, gait aids, prevent fractures
  (Ca, Vit D3, +/- bisphosphonates)
• Dyskinesias-- ?amantadine (no clear evidence)
  Almeida,QJ, Recent Patents on CNS Drug Discovery, 2008:3, 5--54
  PD--Which pharmaceutical?
In Elderly--
• Levodopa/ carbidopa (sinemet) – regular
  vs CR (controlled release)
                  or
Levodopa/ benserazide (prolopa) – regular
  vs HBS

• COMT- inhibitor– entacapone (comtan)
          PD- medications
Levodopa
• Well-established, for bradykinesia and
  rigidity
• SE: nausea, orthostatic hypotension
• Combined with peripheral decarboxylase
  inhibitor (carbidopa, benserazide) to
  prevent conversion to dopamine in the
  periphery before it crosses blood brain
  barrier
            PD- medications
Levodopa (l-dopa)
-- l-dopa / carbidopa = sinemet reg. or CR
-- l-dopa / benserazide = prolopa, medopar or
   medopar HBS
• Competes with amino acids from protein for GI
   absorption
• Regular-- before meals, quick in quick out, T1/2
   = 90 min
• CR--- With meals,Controlled Release, slow in
   slow out, need 30% more to achieve same effect
   as reg. dose, erratic absorption in elderly
           PD-medications
L-dopa cont’d
• SE- Nausea (Rx Domperidone)
    -Hallucinations (Rx lower dose, atypical
  n    neuroleptics)
    -somnolence, confusion, agitation
    -motor fluctuations- after sev yrs of Rx
           PD- medications
L-dopa cont’d

• Motor fluctuations (in 50%, after 5-10yrs)
-wearing-off– Rx COMT – inhibitor*, ?CR
-dyskinesias –(??Rx amantadine??)
-dystonias
-variety of complex fluctuations in motor
  function
          PD- medications
L-dopa cont’d
• Discontinuation—
- gradually –over weeks,
- to prevent malignant neuroleptic like
  syndrome or akinetic crisis
                     PD-medications
L-dopa cont’d
• Dopaminergic dysregulation syndrome (DDS)—
  tolerance to mood elevating effects
- Compulsive use of dopaminergic drugs
- Early onset males
- Cyclical mood disorder
- Impulse control disorder (hypersexuality,
  pathologic gambling)
Giovannoni, G, Hedonistic homeostatic dysregulation…J. Neurol Neurosurg Psychiatry
   2000; 68:243
           PD- medications
COMT – inhibitor
-Catechol-O-Methyl Transferase Inhibitor
-((eg Tolcapone (Tasmar)---off market due to
   fulminant hepatitis causing 3 deaths))
-eg Entacapone (Comtan)
-for wearing-off at end-of-dose of L-dopa
-dose 200mg-1600mg, divided, daily, with L-dopa
-SE-diarrhea in 5%, due to increased
   dopaminergic stimulation from L-dopa
   availability
            PD-medications
Dopamine Agonists: adjunct Rx to L-dopa.
-Ergotamines—bromocriptine, ((pergolide)),
  ((cabergoline))
   SE-same as L-dopa, uncommon Raynaud’s,
  erythromelalgia, retroperitoneal/pulmonary
  fibrosis
-Non-Ergot—pramipexole, ropinirole, ((transdermal
  rotigotine))
   SE—same as L-dopa, Sudden somnolence –
  caution with driving
                  PD-medications
MAO-B inhibitors--adjunct Rx to L-dopa
-eg selegiline (eldepryl), rasagiline
-somewhat helpful in young, early in disease
-neuroprotective properties in animal models
  only
Arch Neurology. 2002; 59:1937
             PD-medications
Anticholinergics—adjunct Rx to L-dopa, best
  avoided in elderly
-acetylcholine (ACh) and dopamine in balance in
  basal ganglia
-decrease Ach to balance decrease in L-dopa
-eg trihexyphenidyl (artane), benztropine
  (cogentin), orphenadrine, procyclidine
  (kemadrin)
-SE-confusion, hallucinations, dry mouth, blurred
  vision, constipation, nausea, u. retention,
  glaucoma
          PD-medications
Amantadine-adjunct to L-dopa, best
  avoided in elderly
-for dyskinesias
-Antiviral agent—mechanism unknown
-NMDA-receptor antagonist properties-
  interferes with excessive glutamate
-SE-livedo reticularis, ankle edema,
  hallucinations
           PD- Medications
When do you stop the medications?
--ALWAYS taper gradually over days to
  weeks to avoid NM-like syndrome
--unable to take meds (dysphagia)
--significant, intolerable SE impairing QOL
--end-stage--- ―infection comes as a friend‖
             OBJECTIVES

1. Illustrate medications and conditions that
  may mimic PD
2. Describe the early symptoms of
  Parkinson’s Disease (PD)
3. Discuss initiating and stopping
  medications