Transcript Parkinson`s and Epilepsy

Parkinson’s and
Epilepsy
Sheelagh Harwell
[email protected]
Please email me if any questions!
Parkinson’s Disease
A chronic degenerative loss of dopamine-containing cells in the
CNS causing a dopamine deficiency.
Parkinsonism
TRAP

Tremor
• Unilateral
• 4-6 Hz
• Pill- rolling
• Worse at rest

Rigidity
• Lead pipe
• Cog-wheeling

Akinesia/Bradykinesia
• Serpentine Stare (Hypomimia)
• Reduced arm swing
• Reduced frequency and amplitude of
• repetitive movements
• Worse with co-stimulation

Loss of Postural reflexes
• Pull test
• Difficulty turning around
• Early falls
Non-motor Symptoms
Autonomic
• Constipation
• Urinary urgency
• Excessive salivation
and sweating
• Postural hypotension
Sensory
• Anosmia
Neuropsychiatric
• Dementia
• Depression
• Anxiety
MEQ
Tremor
Bradykinesia
A 64 year old man attends his GP complaining
of tiredness and “shakiness”. He finds it difficult
to get started walking, feels unsteady on his feet
and generally slower at activities. His wife states
that the shakiness in his hands has gradually
worsened and he gets frustrated trying to fasten
buttons. She has also noticed that his writing
has become very small and barely legible. The
GP suspects this man may have idiopathic
Parkinson’s disease.
Micrographia
Postural instability
a)
Clinical features of Parkinson’s disease
comprise a classical triad. What are they?
Suggest a feature of each that you would
expect to see on examination.
•
•
•
b)
What sensory signs would you expect to see
in Parkinson’s disease?
•
c)
TREMOR
RIGIDITY
BRADYKINESIA
ANOSMIA
Explain how the pathological process
occurring in the brain results in the clinical
features.
Idiopathic Parkinson’s
Disease
 Progressive degeneration of
dopaminergic neurons of
nigrostriatal pathway
(Subtantia Nigra → caudate
nucleus and putamen).
 The loss of dopamine’s
modulatory influence on the
neuronal activity results in
increased inhibitory drive of
the excessively active
GABAergic medial
pallidum/nigra reticulata
neurons. Thus, the end
result of striatal dopamine
loss is inhibition of
cortically initiated
movement (hypokinesia).
 Symptoms arise when 6080% of neurons are lost.
Management
1) Levodopa
 Dopamine cannot cross the blood-brain
barrier as it is too polar.
 L-Dopa is a stereoisomer of Dopa, the
natural amino acid precursor to Dopamine.
 Can cross the BBB via LNAAT (large neutral
amino acid transporter).
 Converted to dopamine by DOPA
Decarboxylase enzyme.
Management
2) DOPA Decarboxylase
Inhibitor
 Stops peripheral metabolism of L-Dopa.
Inhibitor cannot cross the BBB.
 Examples include: Carbidopa and Benserazide.
 Increases bioavailability of L-Dopa from 3% to
33-66%.
 Reduce side effects:
• Postural hypotension
• Nausea
• Hallucinations
3) COMT Inhibitors
 Eg entcapone. Prevents peripheral
breakdown of levodopa to 3-O-methyldopa.
4) MAO‐B inhibitor
 Eg selegiline. Prevents breakdown of
dopamine within synapse.
5) Anti-cholinergic
 Eg atropine. Suppress cholinergic activity eg
tremor, sialorrhoea. Not first line.
Slide by Joe
Sharkey
 Suggest 2 drugs which may be used in
combination with L-Dopa to enhance its activity
and reduce the dosage of L-Dopa needed. 2
Carbidopa, Benserazide, Entcapone
 How do drugs used in combination with L-Dopa
enhance its activity? 1
DOPA Decarboxylase Inhibitor stops
the peripheral metabolism of L-Dopa
and increases L-Dopa bioavailability.
 Give 2 major adverse effects of chronic LDopa administration. 2
 End of dose dyskinesia
 On-off phenomenon
 Suggest 2 drugs which may be used as
alternatives to L-Dopa therapy. 2
 Dopamine agonist – Ropinerole,
bromocriptine.
 MAO-B inhibitor – Selegiline.
Differentials - Parkinsonism
Disease
Key Features
Essential Tremor
Tremor alone, episodic, 10x more common than PD.
Improves with alcohol
Family history
Drug induced
DA agonists- antipsychotics e.g. haloperidol
Antiemetics e.g. metaclopramide + prochlorperazide
Vascular Parkinsonism
 Stepwise progression
Other neuro deficits
CV risk factors
Multi Systems Atrophy
Autonomic features – postural hypotension, erectile dysfunction,
sphincter disturbances
Progressive Supranuclear Palsy
Loss of vertical gaze
Extreme axial rigidity
Fixed facial expression
Any cerebellar disease
Drugs – e.g. Lithium, Phenytoin
Intention tremor
Other cerebellar signs (DANISH)
Wilson’s Disease
Young age
LFTs deranged, LOW serum copper
Post-encephalitic Parkinsonism
Hx of encephalitis
 Parkinson’s disease can be classified
as an akinetic-rigid syndrome.
 List three other examples of akinetic
rigid syndromes?
• Parkinsons plus syndromes – multiple
systems atrophy, progressive
supranuclear palsy.
• Vascular parkinsonism.
• Post-encephalitis parkinsonism
Akinetic Rigid Syndromes
Disease
Key Features
Essential Tremor
Tremor alone, episodic
Improves with alcohol
Family history
Drug induced
DA agonists- antipsychotics e.g. haloperidol
Antiemetics e.g. metaclopramide + prochlorperazide
Vascular Parkinsonism
 Stepwise progression
Other neuro deficits
CV risk factors
Multi Systems Atrophy
Autonomic features – postural hypotension, erectile dysfunction, sphincter
disturbances
Hot cross bun sign on CT
Progressive Supranuclear Palsy
Loss of vertical gaze
Extreme axial rigidity
Fixed facial expression
Any cerebellar disease
Drugs – e.g. Lithium, Phenytoin
Intention tremor
Other cerebellar signs (DANISH)
Wilson’s Disease
Young age
LFTs deranged, LOW serum copper, high urinary copper
Post-encephalitic Parkinsonism
Hx of encephalitis (obvs…)
VODKA signs
Vascular events elsewhere (Vascular
parkinsonism)
Orthostatic hypotension and atonic bladder
(MSA)
Dementia and vertical gaze paralysis (PSP)
Kayser-Fleisher rings (Wilson’s disease)
Apraxic gait (cerebellar disorders)
 Name two classes of drug (with one
example of each) that can cause
parkisonism.
 Atypical antipsychotic eg haloperidol,
chlorpromazine.
 Anti-emetics eg metclopramide
Parkinsonism: select the
most likely diagnosis:
a) A 78 year old man with
known Parkinson’s
disease presents to his
GP as he feels that his
symptoms are
worsening. He
complains that one
minute his arms
completely lock off and
he can’t move them at
all, then the next they
are shaking like a leaf.
a) Idiopathic parkinson’s
disease
b) Drug-induced parkinsonism
c) Post-encephaliopathic
parkinsonism
d) Gilles de la Tourette
syndrome
e) ‘End of dose’ effect
f) ‘On-off effect’
g) Huntington’s chorea
h) Wilson’s disease
i) Progressive supranuclear
palsy
j) Multisystem atrophy
Parkinsonism: select the
most likely diagnosis:
b) A 52 year old woman
presents with a 6
month history of falls
associated with
dizziness. On
examination she has
marked postural
hypotension and is
ataxic.
a) Idiopathic parkinson’s
disease
b) Drug-induced parkinsonism
c) Post-encephaliopathic
parkinsonism
d) Gilles de la Tourette
syndrome
e) ‘End of dose’ effect
f) ‘On-off effect’
g) Huntington’s chorea
h) Wilson’s disease
i) Progressive supranuclear
palsy
j) Multisystem atrophy
Parkinsonism: select the
most likely diagnosis:
c) A previously fit and well
71 year old man
presents to the GP with
a productive cough.
However, while he is
there the GP notices
that he has a stooped
posture, takes small
shuffling steps when he
walks and has poor
‘swing through’ of the
right upper limb. He
also notes cogwheel
rigidity of the right
upper limb.
a)
b)
c)
d)
e)
f)
g)
h)
i)
j)
Idiopathic parkinson’s disease
Drug-induced parkinsonism
Post-encephaliopathic
parkinsonism
Gilles de la Tourette syndrome
‘End of dose’ effect
‘On-off effect’
Huntington’s chorea
Wilson’s disease
Progressive supranuclear
palsy
Multisystem atrophy
Parkinsonism: select the
most likely diagnosis:
d) A 48 year old man
presents to his GP with
what he describes as
increased frequency of
tics. He has
uncontrollable, brief, jerky
movements that flit from
one part of the body to
another.
a)
b)
c)
d)
e)
f)
g)
h)
i)
j)
Idiopathic parkinson’s disease
Drug-induced parkinsonism
Post-encephaliopathic
parkinsonism
Gilles de la Tourette
syndrome
‘End of dose’ effect
‘On-off effect’
Huntington’s chorea
Wilson’s disease
Progressive supranuclear
palsy
Multisystem atrophy
Parkinsonism: select the
most likely diagnosis:
e) A 19 year old man is
referred to neurology
outpatients with
‘features of parkinson’s
disease’. His liver
function tests are
deranged and he has
reduced copper and
caeruloplasmin levels.
a)
b)
c)
d)
e)
f)
g)
h)
i)
j)
Idiopathic parkinson’s disease
Drug-induced parkinsonism
Post-encephaliopathic
parkinsonism
Gilles de la Tourette
syndrome
‘End of dose’ effect
‘On-off effect’
Huntington’s chorea
Wilson’s disease
Progressive supranuclear
palsy
Multisystem atrophy
Epilepsy
 Recurrent transient paroxysmal attacks
of disturbed consciousness and
sensorimotor function, resulting from
abnormal electrophysiological
discharges of cerebral neurons.
 Anti-epileptic drugs (AEDs) are usually
recommended after 2nd seizure.
 Epilepsy remits in 70%.
AEDs
1. Valproate – generalised seizures. Broad
spectrum. Teratogen. Monitor LFTs.
2. Carbamazepine – partial seizures. Few
side effects. Interacts with p450 system.
3. Phenytoin – narrow therapeutic window.
Monitor. Many side effects.
4. Lamotrigine – works for almost all forms.
Interacts with valproate. Not teratogenic.
Severe skin reactions in 3% especially
children.
Epilepsy
A 16 year old schoolgirl with known
epilepsy is brought into hospital by
her mother. The girl is obviously
having a prolonged tonic-clonic
seizure. Her mother is very anxious,
as the seizure has lasted more than
30 minutes.
Medical
a) What is the diagnosis? emergency
Status epilepticus
b) The girl’s mother says her daughter
has been going through a ‘difficult
stage’ and is unsure if she has been
taking her anti-epileptic medication
regularly. Suggest 3 other causes for
this presentation?
 Alcohol
 Recreational drugs
 Infection
 Inadequate drug/dose
c) You obtain IV access immediately and send
off urgent bloods. Suggest 3 important tests
in this situation?
 Anticonvulsant levels
 Toxicology
 Calcium
 Glucose
 FBC
 LFTs
 U&E
d) What two immediate treatments do you
institute?
 60% Oxygen via a trauma
mask/oropharyngeal tube.
 IV lorazepam single dose 4mg. Repeat
once if necessary after 10 minutes.
e) The girl is still fitting so you start an IV
infusion. What is your drug of choice?
 IV phenytoin infusion (15ml/kg over 20
minutes).
 ECG monitoring (dysrhythmias).
If seizures continue for >30mins despite
tx, then GA (thiopentone iv bolus then
infusion) for >12 hours. Monitor EEG.
Thanks!