Movement Disorders

Oliver Bandmann, MD PhD

Professor of Movement Disorders Neurology/
Consultant Neurologist

Mov dis - why bother?

Mov dis are common
Prevalence PD: 3% > 65 yr.
Prevalence essential tremor: 5% > 65 yr.
Mov dis are fun because they are pure medicine
Diagnosis is mostly based on taking the history and physical
examination
If you know what you have to ask and look for, you wont
need any fancy tests!
Mov dis you can help!
Parkinsons disease
Essential tremor
Dystonia

Efficient drug treatment available

Age related prevalence of Parkinsons Disease

1400
1200
1000
800
600
400
200
0
0-29 30-39 40-49 50-59 60-69 70-79 >80

Number of cases per 100,000

Basal ganglia anatomy and disease

Hardware problem:
Parkinsons disease
Huntingtons disease

Software problem:
Essential tremor
Dystonia
Tourette

Structure of this talk

Parkinsons disease

Symptoms
Signs
Aetiology
Treatment

Differential diagnosis:
History red flags
Examination red flags

Mr Smith, 68 yr., Hx
First Symptom: Stiffness left leg
Wife adds: He walks more slowly, seems to drag his left leg

Subsequently gradual worsening:

Tremor left hand
Problems with doing up buttons
Writing smaller
Stiffness left leg
Reduced arm swing

Most symptoms in PD can be attributed to three

cardinal features:
Brady/Akinesia
Problems with doing up buttons, keyboard etc
Writing smaller
Walking deteriorated: Small stepped, dragging one foot etc

Tremor
At rest
May be unilateral
Rigidity
Pain
Problems with turning in bed

Mr Smith - findings on examination

Small stepped gait with:
stooped posture, reduced armswing, L > R
Increased tone = rigidity
Tone increased over entire radius of joint movement

Rest tremor
Often asymmetrical, also some postural tremor
Decreasing amplitude/accuracy of repetitive movements
Much better at the beginning, gradual worsening

Some questions from the patient

Where is the damage?
What is the cause of PD?

What is my prognosis?

PD - Pathology
Normal

PD

Normal

PD

Lewy body

The reduced dopamine supply to the striatum

can be made visible in living patients

PET Scan

Susceptibility
factors

Parkinson
Genes
Inherited factors

Oxidative
stress

Cell loss in
substantia nigra

Mitochondrial
dysfunction

Environmental factors
Risk factor

Toxin induced

Prognosis
Be honest but kind!
The disease is slowly progressive

It does not change its nature over night

You are the expert

 Is there any treatment?

No cure
No disease-modifying treatment
Plenty of symptomatic treatment options, aim:

Compensate for loss of dopamine

Therapy of Parkinsons disease

keeping the balance

L-Dopa
L-Dopa

Dopamine

Dopamine receptor

Dopamine agonists

Dopamine agonist

Dopamine

Dopamine receptor

COMT/MAO-B
inhibitors

Catechol-O-MethylTransferase
Monoaminooxidase

Dopamine
Dopamine receptor

Anticholinergics?

Many side-effects:
Cognition
Confusion
Systemic

Motor complications of late-stage PD

Wearing off
Medication doesnt work as long as before
On-Dyskinesias
Hyperkinetic, choreiform movements whenever drugs
work
Off-Dyskinesias
Fixed, painful dystonic posturing, typically of feet,
when drugs dont work
Freezing
Unpredictable loss of mobility

When should treatment for motor symptoms be

started?
Nobody knows
Major push from drug companies to get patients started on
treatment early
Factors to take into consideration:
Severity of motor impairment/QoL
Side effects
Myths
L-Dopa - phobia
Neuroprotection???
As always, look at each individual patient and try your best
to decide together with him!

Which drug?
L-Dopa vs DA Agonist vs MAO-B inhibitor
MAO-B inhibitor (Rasagiline Selegiline)
Not very powerful, but does help some patients
If any of the currently licensed PD drugs have neuroprotective effect, it s
this one!

DA Agonist (Ropinirole, pramipexole, Rotigotine Patches)

Reduced risk of dyskinesias in the short-medium term
First line drug treatment of younger PD patients (< 60 yr)
Significant soft side-effects: Tiredness, gambling, hypersexuality etc

L-Dopa
Most powerful drug
The higher the dose, the greater the risk of SE

L-Dopa Make good use of all three different preparations!

Dispersible L-Dopa - Kick- start in the morning

Standard Release Day time medication

Slow release night time

Mr Smith, 6 months later

Definite improvement of motor features
But:

Feels anxious
Wakes up early, cant go back to sleep
Worries a lot
No longer enjoys his hobbies

PD - not just a movement disorder!

Depression very common (20 40%)

Other psychiatric problems:

Phobias, anxiety disorder, hallucinations
Dementia (20%)
Particularly old, severely affected pat
Autonomic problems
Constipation (> 2/3 of all pat > 60 yr)
Increased urinary frequency
Urinary incontinence not typical

Sleep disorders
Depression/psychosis/dementia

Constipation
Parkinsonism

Anosmia

Autonomic dysfunction

DA system is just the tip of the iceberg

Substantia nigra

Amygdala

Pons
Cortex
Olfactory bulb

Spinal cord

Peripheral autonomic system

Muscle?

Skin?

Blood?
Langston, 2006

Slowly progressive walking problems

is it really PD?
Incontinence

Dementia
None of these should be present in PD
Symmetry
Early falls

(at least at the beginning)

(Not so) Normal Pressure Hydrocephalus

Normal

Magnetic gait
Incontinence

Dementia

Surgical correction:
A bit of plumbing (shunt)
can result in improvement of:
Dementia
Incontinence
Walking problems
But: Only if somebody
makes the right diagnosis!

Mrs Duncan, 56 yr, Hx

Referral letter: ? PD

Onset 3 yrs ago with tremor right hand

Gradual worsening
Tremor typically present on action, not at rest
Better after a glass of Sherry!
Mother and sister also affected
No additional problems such as deterioration of walking,
fine finger movements etc

Mrs Duncan, examination:

Postural/action tremor
No/little rest tremor

No increased tone
No problems with fine finger movements

Diagnosis:
Essential tremor

Very common
No structural pathology
Cause? Software problem

ET - treatment
Take it seriously!
1/3 of pat have to re-train!

Beta-blockers
Up to 100 mg bd
Contraindicated in pat with asthma or diabetes

Primidone
Start off with low doses

Others
Gabapentin, Topiramate, clonazepam (?)

Next patient.

64 yr old
Slowly progressive walking problems
Deterioration of fine finger movements
Slurred speech

No findings on examination
Broad based gait
Not small, narrow steps

Intention tremor
Not rest (postural) tremor

Normal tone
Not rigidity

Clumsy
Not decreasing amplitude of FFM

Diagnosis?

Cerebellar Ataxia

Normal

Cerebellar atrophy

Huntingtons disease
cardinal features
Chorea
Dementia
Psychiatric problems

Positive family history

HD History/Symptoms
Chorea
Fidgety
cant sit still
Patient often not aware of abnormal movements

Dementia
Memory problems

Psychiatric problems
Personality change
Depression
Psychosis

HD findings on examination
Abnormal eye movements
Problems with initiating saccades
Broken pursuit

Chorea
Chorea = dance
Random, unpredictable
Pat often tries to make the movements look normal

Ataxia
Problems with heel to toe walking

Often additional touch of parkinsonism

Rigidity
Slowness of fine finger movements

Triplett disorders
a bit too much of something normal

HD conventional treatment
Chorea
Neuroleptic - Sulpiride

Depression
Selective serotonine reuptake inhibitors/Seroxate

Psychosis
Neuroleptics - Haloperidol

Aggression
Risperidone

Generalized Dystonia
Often positive family history
Typically onset in childhood
Software problem, no cell death

Dystonia is syndrome of sustained muscle

contraction, frequently causing twisting and repetitive
movements as well as abnormal posture

Questions?