neurodegenerative disorder

severe loss of pigmented dopaminergic neurons in substantia nigra of midbrain

neurons project to corpus striatum - leads to overall decrease in motor activity

not fatal in itself but: falls, #, chest infections 2ary swallowing disorder - increase mortality in PD

Braak theory

• pathology first starts in eneteric nervous systme and in medulla and olfactory bulb

• then to substantia nigra

• precede motor symptoms;

  • constipation and other autonomic symptoms

    • sweating

    • drooling @ night

    • erectile dysfunction

  • Hyposmia (decrease smell)

  • REM sleep disorder

  • severe depressive disorder

  • fatigue and/or mental infelxibility

  • lower back pain

epidemiology + genetics

• 1% > 65

  • 3/1000 patients

• median age onset = 60yo

• life expectacy \~ 15yrs

Features

Characteristic symptoms:

• stiffness

• resting tremor

• bradykinesia

  • handwriting

    • typically slopes upwards

• hypokinesia (reduction of movement)

• asymetric

• insidious

• non motor;

  • excessive sweating

  • deression

  • reduced sense of smell

  • cognitive impairment

    • alterante = lewy body dementia

  • hypotension (?)

    • early hypotension = MSA

  • not useful in diagnosing PD limited specificity

Examination

• rigidity

  • passive movements

  • ‘cogwheel phenomenon

• resting tremor

  • 4Hz (4 cycles / sec)

  • typically affecting upper limb

• impairment of dextrous upper limb movements and facial expression due to bradykinesia

  • affecting small muscle groups of face and hands

    • usually seen in the early phases of the condition

• gait disorder

  • later in course

  • lack of spontaneous arm swing

  • turning en bloc

    • whole body turns when changing direction

  • festinating gait

    • small steps

    • shiffling

  • falls

Diagnosis

• diagnosis = challenging

• recommend specialist opinion (neurology vs. geriatrician) before treatment is initiated

  • improve likelifood of a good outcome

• response to levodopa = key criterion for diagnosis of PD

• alternative dx

  • medicine-induced parkinsonism

  • essential tremor

  • multiple cerebral infarction

Management

no cure

symptom control

treatment = functional benefit for at least 10yrs

non-pharmalogical

multidisciplinary approach”

• PT

• OT

• Speach language

• nurse

• specialist

• GP

Exercise

• formal exercise rehabilitation likely to benefit patients

• PT specific interventions

  • start hesitancy

  • freezing of gait

  • festination

  • fals

• 1. Strategy training

  2. Managmeent of musculskeletal issues

     1. weakness

     2. loss of ROM

  3. General promotion of physical activity with specific interventions for falls prevention

no evidence that one measure better than any others; quality of comparisons were poor

Occupational therapy

• safely maintain activity and employment

• improve self esteem

• also to determine re driving motor vehicle

Driving:

cognitive disturbance, adverse effect of dopaminergic treatment (daytime sleepiness)

limb strenght, accuracy of rapid foot movements, joint proprioception should be assessed

should always cease if there is doubt about a person’s ability to control a vehicle in an emergency situation

 if trouble walking then trouble driving 

Speech therapy

• hypophonia (soft speech)

• voice training can improve voice quality and audibility

• SLT - focus on iincrease on volume of speech

• dysphagia

Dietician

• weight loss - some people

  • extra energy expenditure

    • tremor/rigidity

    • change swallowing

    • satiety

    • reduced appetite due to dopaminergic treatment

• may benefit from high calorie supp. but little evidence

Parkinson’s NZ website

www.parkinsons.org.nz

counselling for the patient

• can assis in the development of self-management techniques - depression and anxiety

• strain on families

Pharmacological treatment

• motor symptoms tycially respond well

  • response = diagnositc criteria

• motor symptoms controlled = on

• poor motor symptom control = offf

• little evidence that treatment in early phases results in improved long-term outcomes

• if doens’t respond consider other diagnosis

• motor fluctuations

  • dyskinesia 2ary levodopa treatment develop in all patients with PD

• ‘wearing off’ phenomenon

  • increase stiffness adn slowness after dose of med

  • very severe fluctuations between rigid-akinetic states adn severe episodes of dyskinetic (involuntary) movements

When to start

• reports troubling sympomts

• neurologist/geriatrician responsible for initiating treatment

• diagnostic trials not considered without discussion with a neurologist or geriatrician

• if delay -> phone

Levodopa + dopa-decarboxylase inhibitor

• usually firstline

• dopamine doesn’t cross b-b barrier - causes severe N&V when given at high doses (enought to cause motor effect)

• Levodopa does cross

  • rapidly metabolised to dopamine by decarboxylase - in peripehry as well as in brain

    • therefore must be administered with peripheral decarboxylase inhibitor

    • carbidopa or beserazide

Patients over 40:

• combination levodopa = first line

• swallowed whole - not halved or broken

• often need to increase doses of levodopa or add dopamine agonists

• dose sdjusted according to level of diability

• severity of patient’s dyskinesias often determine maximum dose and length of time that levodopa can be tolerated

• modified release doesn’t reduce motor fluctuations

Patients \<40

• dopamine agoinist

• b/c likelifood developing motor fluctuations within 5yrs = 100%

  • ropinirole or pramipexole

  • also frequently used in combination wiht levodopa

  • ‘smooth-out’ motor fluctuations

  • cause more sleepiness

  • impulse control disorders

    • binge eating

    • compulsive shopping

    • gambling

    • hypersexuality

• bromocriptime/pergolide (ergot-derived)

  • no longer prescribed due to possibility of cardicac valvular fibrosis, pulmonary fibrosis, retroperiotoneal fibrosis

  • need to be monitored for these complications

MAOi-B

• mild symptoms

• Selegiline

  • can delay need for levodopa

  • alone or combination

  • inhibits catabolism of dopamine

  • may also be combined with levodopa

Amantadine

• weak dopamine agonist

• can be used to treat dyskinesia

• not first-line

• modest effect

• last less htan 8 months

  • although recent trial suggests may last for several years

Catechol-O-methyltransferase inhibitor may be added later in treatment

• end-of-dose deterioration

• COMT inhibitors - entacapone, tolcapone

• prevent peripheral conversion

antimuscarninc medicines less effective compared to dpopaminergic treatments

Non-motor sympotms

Cardiovascular

• postural and post prandial hypotension

  • increase fluid/salt

  • frequent small meals

  • compression stocking

  • anti-hypertensive meidicnes used with caution

  • fludrocortisone 50mcg daily

Gastrointestinal

• Drooling

  • dopaminergic/antimuscarinic medicines

    • reduce drooling

    • usually cause adverse effects

    • 1% atropine eye drops administered sublingually

• dysphagia

  • partially responsive to dopaminergic

  • thickened fluids reduce risk of aspiration

  • SLT

• gastroparesis

  • eat small meals

  • domperidone 10-20mg tds/qds

    • dopamine antagonist that doesn’t cross B-B barrier

• constipation

  • increase fluid/fibre

  • laxatives

  • bisacodyl (stimulant)

  • glycerol supp

  • docusate

  • docusate + sennosides shouldn’t be takien for long periods

• pain

  • pain present during On or off

    • adjusting dopamimnergic treatment may provide benefit

  • can be caused by restricted movmeent

  • muscle spasm

  • nortrip/amitrip

  • carbamazepine 100mg od or bd - increase according to response

  • gabapentin - max 3.6g

• Cognitive

  • anxiety

    • “off” state anxiety may benefit from increase dopaminaergic treatment

  • depression

    • assess for pain or sleep disturbance

    • TCA/SSRI may be appropriate

    • support and counselling

  • Hallucinations

    • non-troubling don’t require treatment

    • Quetiapine may be used with extreme caution

  • Dementia

    • clozpaine

      • requires weekly FBC

• genitourinary

  • Urgency/frequnecy/bocturia/incovontinence

    • avoid diuretic

    • oxybutyinin in cautino

• Sleep

  • excessive daytime sleepiness

    • fatigue 1/3 of PD

    • less common taking levodopa compared to dopamine agonists

  • nocturnal doses of dopaminergic medicine may assis t with insomnia

  • levodopa and dopamine agonists may help pateinets wiht RLS

  • Methylphenidate 1-mg tds may be useful

  • benzodiazepine may be effective for patients with REM sleep disorder