Thursday 7 October 2010

MRCP revision battle 26.1: Parkinson's disease

I'm back on the revision bandwagon and am ready for another 7 battles...

MRCP revision battle 26.1: Parkinson's disease
MRCP revision battle 26.2: Lewy Body Dementia
MRCP revision battle 26.3: Malignant hyperthermia
MRCP revision battle 26.4: Benign intracranial hypertension
MRCP revision battle 26.5: Coarctation of the aorta
MRCP revision battle 26.6: Heparin
MRCP revision battle 26.7: Essential tremor

MRCP revision battle 26.1: Parkinson's disease/Parkinsonism

Parkinsonism is a triad of:
  • resting tremor (3 to 5 Hz)
  • rigidity
  • bradykinesia
 There is also loss of postural reflexes.

It is Parkinson's disease if there is degeneration of the substantia nigra dopaminergic neurones with Lewy bodies.

There are a whole list of associated features that I'm sure you're familiar with, but if you fancy a brief recap read the list below...
  • expressionless, mask-like face
  • dribbling
  • festinant gait = short shuffling steps with flexed trunk)
  • micrographia

Management of Parkinsons is by a multidisciplinary team and the pharmacological management of it is notoriously tricky, with multiple drugs which often decrease in efficacy with use and may result in 'on-off' symptoms.

Even the NICE guidelines recognise the challenge in drug prescription, stating that "it is not possible to identify a universal first-line drug choice".  They single out the following as possible first line options:
  • levodopa
    • use lowest dose possible
    • give with carbidopa to prevent peripheral breakdown
    • is of no use in neuroleptic induced Parkinsons
  • dopamine agonists
    • bromocriptine*, cabergoline*, ropinole
    • if an argot-derived agonist is used (*) ESR, UEs and CXR should be done before starting and annually while on treatment
  • MAO-B inhibitors
    • selegiline
    • decreases dopamine breakdown

Second line treatment is combining the above options, or one of the above with:
  • COMT inhibitors
    • entacapone
    • inhibit dopamine breakdown

Other medications which may be useful for specific effects include:
  • amantidine
  • apomorphine
  • antimuscarinics
    • procyclidine
    • more useful for drug-induced Parkinsons

A couple of other key points from the NICE guidelines on Parkinsons are:
  • 'drug holidays' should not be undertaken due to risk of neuroleptic malignant syndrome on restarting
  • clinicians should be aware of dopamine dysregulation syndrome, which is an uncommon disorder in which misuse of dopaminergic medication is associated with behaviours such as hypersexuality, pathological gambling and sterotypic motor acts

For the really keen:

For everyone else, lets move on to Lewy body dementia.

MRCP revision battle 26.2: Lewy Body Dementia

Lewy Body Dementia accounts for around 20% of cases of dementia.

The key feature is Lewy Bodies (=intracytoplasmic neuronal inclusion bodies) in substantia nigra, paralimbic and neocortical areas.

Since this would obviously only be confirmed post-mortem diagnosis is made clinically:
  • Parkinsonian features
  • fluctuating cognitive loss
  • visual hallucinations

Neuroleptics must be avoided as their use would risk inducing irreversible Parkinsonism.

Treatments which may help include donepezil and rivastigmine.

Next up - malignant hyperthermia

MRCP revision battle 26.3: Malignant hyperthermia

Malignant hyperthermia is a rare, life-threatening condition in which there is a huge increase in the body's skeletal muscle oxidative metabolism, resulting in:
  • hypercapnia
  • increased oxygen consumption
  • hyperthermia (T>38C)

Secondary problems which may develop from malignant hyperthermia include:
  • renal failure
  • arrhythmias
  • DIC

Malignat hyperthermia may be caused by:
  • any inhaled anaesthetic agent
  • Succinylcholine  

It is often inherited in an autosomal dominant fashion.

Treatment is with dantrolene.

Onwards to benign intracranial hypertension...

MRCP revision battle 26.4: Benign intracranial hypertension

Benign intracranial hypertension classically affects overweight young females.

It presents like there should be a mass in the brain, but none can be found.

Features include:
  • headache
  • blurred vision
  • dizziness
  • horizontal diplopia
  • papilloedema

Benign intracranial hypertension is associated with:
  • COC
  • steroids
  • tetracyclines
  • vitamin A
  • nitrofurantoin
  • isontertinoin
  • danazol

Management is:
  • weight loss
  • acetazolamide
  • loop diuretics
  • prednisolone
  • therapeutic lumbar puncture
  • shunt

Note that up to 10% of patients have permanent significant vision loss - so its name of 'benign' is a little misleading!  Optic nerve sheath fenestration can help prevent this.

Onwards for a spot of coarctation of the aorta...

MRCP revision battle 26.5: Coarctation of the aorta

Coarctation of the aorta (=narrowing of the aorta) classically occurs just distal to the left subclavian artery.

It may present at birth with heart failure, or be discovered later in life, eg during investigation for hypertension.

Most adults with coarctation of the aorta are asymptomatic.  Occasionally they may complain of:
  • headache
  • recurrent epistaxis
  • claudication of the calf muscles

Clinical examination may reveal:
  • radio-femoral delay
  • midsystolic murmur

Complications of coarctation include:
  • hypertension
  • LVF
  • endocarditis

Conditions associated with coarctation include:
  • bicuspid aortic valve (10-20%)
  • PDA
  • VSD
  • Berry aneurysms
  • Turners syndrome
  • renal abnormalities

CXR may show rib notching due to formation of collaterals

Management is stenting/surgery.

Now for the penultimate battle of the day, heparin...

MRCP revision battle 26.6: Heparin

Heparin comes in 2 'flavours':
  1. low molecular weight heparin (AKA dalteparin/fragmin, enoxaparin/clexane, tinzaparin) 
  2. unfractionated (AKA 'heparin')

So what are the differences?
  • molecular weight
    • LMW heparin, as the name suggests, has a lower molecular weight - 5000 compared to unfractionated heparin's 13000
  •  half life
    • LMW heparin has a longer half life than unfractionated heparin
  •  mechanism of action
    • LMW heparin inhibits factor Xa but has little effect on antithrombin
    • unfractionated heparin binds antithrombin
  • affect on aPTT
    • LMW heparin has little effect on aPTT
    • unfractionated heparin prolongs aPTT
  • side effects
    • both can cause osteoporosis and thrombocytopenia but the risks are greatest with unfractionated heparin
  • reversibility
    • unfractionated heparin can be fully reversed by protamine
    • LMW heparin cannot be fully reversed by protamine

A side effect of protamine to be aware of is hypotension.

HIT (=heparin induced thrombocytopenia) is a potentially serious side effect of heparin use which will be covered tomorrow.

With that to look forward to lets shake on to the last battle of the day, essential tremor...

MRCP revision battle 26.7: Essential tremor

Essential tremor can be sporadic or inherited; if inherited its inheritance pattern is believed to be autosomal dominant with incomplete penetrance.

35% of patients with essential tremor will have no family history.

It tends to be worse when the arms are outstretched.

Essential tremor improves with alcohol (not advised as a treatment option!)

Treatment tends to be:
  • propranolol
  • primidone if propranolol contra-indicated (eg in asthma)

Congratulations on surviving another day's battles!