MRCP revision battle 31.1: Wernicke's Encephalopathy

Day 2 of 3 for lots of neuro...


MRCP revision battle 31.1: Wernicke's Encephalopathy
MRCP revision battle 31.2: Korsakoff's Syndrome
MRCP revision battle 31.3: Multiple Sclerosis
MRCP revision battle 31.4: Menieres Disease
MRCP revision battle 31.5: CJD
MRCP revision battle 31.6: Herpes Zoster Opthalmicus
MRCP revision battle 31.7: Ramsey Hunt Syndrome




MRCP revision battle 31.1: Wernicke's Encephalopathy


Wernicke's encephalopathy is caused by thiamine (=vitamin B1) deficiency.


The classic triad associated with Wernicke's encephalopathy is:

• opthalmoplegia
• ataxia
• confusion

There may also be hypothermia and hypotension.


Thiamine deficiency may result from:

• alcoholism
• carcinoma of stomach
• anorexia
• vomiting

CT brain may show petichial haemorrhages and a low red cell transketolase blood test could prove thiamine deficiency (rarely performed)


Treatment is parenteral thiamine (pabrinex)

If untreated, 20% of patients will die and 85% will develop Korsakoffs.


Which leads us nicely into revision battle 31.2: Korsakoffs syndrome....

MRCP revision battle 31.2: Korsakoff's Syndrome

Korsakoff's Syndrome is a condition in which there is an inability to build new memories but preservation of other cognitive functions.


It is a chronic disorder, usually following Wernicke's encephalopathy.


The patient has an inability to consolidate new info, retrograde amnesia, patchy preservation of long term memory, a lack of insight and confabulates (=fabricates information to make up for memory loss)


Treatment is with thiamine but under 20% of patients respond.


On to 31.3... MS...

MRCP revision battle 31.3: Multiple Sclerosis

Multiple sclerosis is a cell-mediated autoimmune disorder characterised by plaques of demyelination at sites throughout the CNS but not in the peripheral nerves.


4 main types:

1. relapsing-remitting
• accounts for 80% of cases
2. secondary progressive
• up to 50% of relapsing-remitting patients eventually develop this
3. primary progressive
• 10-15% of cases
• older age of onset
4. progressive-relapsing

Initial presentation tends to be a single symptom, such as:

• optic neuritis 
• pain on eye movement and rapid deterioration in central vision, loss of colour vision
• treatment is methylpred
• single episode gives 40-60% chance of subsquent MS
• numbness or tingling in limbs
• leg weakness
• ataxia

Diagnosis is by (NB none is specific):

• lesions disseminated in time and location
• T2 weighted MRI showing demyelinating plaques
• delayed visual evoked response potentials
• oligoclonal bands in CSF but not serum

Good prognostic factors are:

• relapsing-remitting course
• female
• young onset
• sensory symptoms

Risk of MS is increased 20-40% in siblings and there is 25% concordance in monozygotic twins.



Treatment is:

• IV methylprednisolone
• shortens relapses
• no effect on incidence of attacks
• beta interferon
• decreases relapses by 30%
• given if
• relapsing-remitting course and 2 relapses in 2 yrs and can walk 100m unaided
• secondary progressive and 2 relapses in 2 yrs and 100m aided
• side effect: flu-like
• baclofen
• decreases spascity

Now for the less heavy-going Menieres disease...

MRCP revision battle 31.4: Meniere's Disease

Meniere's Disease is a disorder of the inner ear causing vertigo and hearing loss.


Features include:

• vertigo
• tinnitus
• sesorineural hearing loss
• aural fullness

There may be nystagmus and a positive romberg's test


It is usually unilateral and is believed to be associated with endolymphatic hydrops (=increased fluid in ear)


Rarely it may be associated with drop attacks - no LOC or vertigo, but suddenly falling to one side.


Management:

• prochlorperazine
• inform DVLA and stop driving until controlled.

 Next up: that formally very topical topic CJD...

MRCP revision battle 31.5: CJD

Creutzfeldt-Jakob Disease (=CJD) is a prion disease which causes a rapidly progressive dementia with myoclonus.



The majority of cases are sporadic.  There is also an inherited form and an acquired form (=varient CJD, from meat infected with BSE)


CSF examination is usually normal but EEG shows characteristic biphasic high-amplitude sharp waves.


Death is usually within 6 months.


On a lighter note lets look at herpes zoster opthalmicus...

MRCP revision battle 31.6: Herpes Zoster Opthalmicus

Herpes zoster opthalmicus is the reactivation of varicella zoster in the area supplied by the opthalmic division of the trigeminal nerve.


It occurs in roughly 10% of cases of shingles.


There may be Hutchinson's sign = rash on the tip of nose, which indicates nasocillary involvement and is a strong risk factor for ocular involvement.


Treatment is oral antivirals for 7 to 10 days and urgent opthalmic review if there is ocular involvement.



On to the final revision battle of the day...

MRCP revision battle 31.7: Ramsey Hunt Syndrome

Ramsey Hunt Syndrome is the reactivation of varicella zoster in the geniculate ganglion of the facial nerve.  


It is characterised by:

• herpes zoster oticus (=herpetic eruption in external auditory meatus)
• facial nerve palsy
• +/- deafness, tinnitus and vertigo

Treatment is with oral antivirals

MRCP revision battle 30.1: Retinitis Pigmentosa

Today is the start of a 3 day neuro/opthalmology blitz, so hold on to your hats....


MRCP revision battle 30.1: Retinitis Pigmentosa
MRCP revision battle 30.2: Oculogyric Crisis
MRCP revision battle 30.3: Myotonic Dystrophy
MRCP revision battle 30.4: Trinucleotide repeat disorders
MRCP revision battle 30.5: Huntington's Chorea
MRCP revision battle 30.6: Friedreich's ataxia
MRCP revision battle 30.7: Alzheimer's Disease




MRCP revision battle 30.1: Retinitis Pigmentosa

Retinitis pigmentosa is a type of progressive retinal dystrophy which eventually leads to blindness.

It has a very characteristic fundoscopic appearence with black mottling of the retina and a pale optic disc, as illustrated below in an image by Christian Hammel (from wiki commons):

It can be inherited in an autosomal dominant, autosomal recessive or X linked recessive fashion.



Night blindness is often the first sign.
Later comes funnel/tunnel vision.


It is associated with many conditions, including:

• Kearns Sayre (remember battle 15.1?)
• Ushers syndrome = retinitis pigmentosa with sensorineural deafness
• congenital toxoplasmosis

There is no cure for retinitis pigmentosa but progression of the disease can be slowed by vitamin A.



On to the second battle of the day...

MRCP revision battle 30.2: Oculogyric Crisis

The key features of an oculogyric crisis are restlessness and upward deviation of the eyes (although this only occurs in severe cases).


Oculogyric crises may be precipitated by a range of drugs including:

• neuroleptics
• metoclopramide/domperidone
• nifedipine
• TCA
• carbamazepine

Several clinical conditions can also cause oculogyric crises, for example:

• parkinsons disease
• post encephalitis
• bilateral thalmic infarction
• MS

Treatment is with procyclidine, an anticholinergic.


On to the next battle...

MRCP revision battle 30.3: Myotonic Dystrophy

Myotonic dystrophy is an autosomal dominant condition in which there is muscle weakness and myotonia.  It is a trinucleotide repeat disorder.

Onset tends to be in the 30s.


There are 2 types:


Dystrophia myotonica (=DM) 1

• 98% of cases
• more severe
• distal muscle weakness
• chromosome 19

Dystrophia myotonica 2:

• 2% of cases
• less severe
• proximal muscle weakness
• chromosome 3

Features associated with myotonic dystrophy include:

• long faces
• frontal baldness
• myotonia and weakness
• testicular/ovarian atrophy
• bilateral ptosis
• cateract
• cardiomyopathy
• diabetes
• miotic pupils 
• mildly decreased IQ

It is incurable but phenytoin can improve the myotonia.


Lets move on to consider an overview of trinucleotide repeat disorders

MRCP revision battle 30.4: Trinucleotide repeat disorders

Trinucleotide repeat disorders are conditions in which 3 nucleotides in the DNA are expanded.

The most 'famous' are:

• Huntingtons chorea (CAG) - covered in next battle
• Fragile X (CGG)
• Myotonic dystrophy (CTG) - covered in previous battle
• Friedreichs ataxia (GAA) - covered in battle 30.6

Two concepts to be born in mind for trinucleotide repeat disorders are:

Anticipation = the disease presents earlier and is worse in successive generations

Somatic instability = expansion increases as patient gets older


So lets briefly cover the most famous, Huntingtons...

MRCP revision battle 30.5: Huntington's Chorea

Huntington's chorea is an autosomal dominant condition due to CAG repeats.

It is carried on chromosome 4.


Symptoms tend to start in the 40s with a progression from chorea to irritability to dementia and death.


There is no cure.  The chorea may be treated with a dopamine antagonist such as tetrabenazine.



Note that Hunington's has complete penetrance so a child of a sufferer has a 50% chance of being affected.  Due to anticipation if they are affected they are also likely to develop symptoms earlier.



Next up: Friedreich's ataxia...

MRCP revision battle 30.6: Friedreich's ataxia

Friedreichs ataxia is an autosomal recessive trinucleotide repeat disorder (GAA)


It causes degeneration of nerve tracts resulting in cerebellar ataxia, dysarthria, nystagmus and dysdiadocholokinesis.


Muscles are weak, reflexes are depressed but plantars are upgoing.


There is often scoliosis and high arches of the feet.

Cardiomyopathy is another complication.


There is no cure.


Lets now try and forget all these incurable diseases with a touch of Alzheimer's...

MRCP revision battle 30.7: Alzheimer's Disease

Alzheimer's disease is the leading cause of dementia.  This battle aims to pick out a few juicy facts for MRCP; http://alzheimers.org.uk/ can provide more in-depth information if you are interested.


The earliest symptom of AD is typically forgetfulness.



5% of cases are autosomal dominant, with chromosomes 1, 14, 19 and 21 implimented.

After age, apoE4 (chromosome 19) is the most significant risk factor for AD.


Beta amyloid plaques and hyperphosphorylated tau protein tangles are found within neurones post-mortem.
The density of the tangles can correlate with the severity of the dementia.




Hippocampal atrophy is prominant.





Cholinesterase inhibitors such as donepezil, rivastigmine and galantamine are licensed for patients with a MMSE of between 10 and 20.

Memantine (an antiglutamatergic) may be useful in severe AD.



As Bugs Bunny would say, thhhhatttttts alll folllkkkksss.... until tomorrow!

MRCP revision battle 29.1: Hypoglycaemia

After nearly a week away I'm back with a bumper set of battles, the first of which is hypoglycaemia, which has been a recurring theme in both my patients and myself this week!  Enjoy!


MRCP revision battle 29.1: Hypoglycaemia
MRCP revision battle 29.2: Thyroid eye disease
MRCP revision battle 29.3: Hyperlipidaemia
MRCP revision battle 29.4: Lipid-lowering treatment
MRCP revision battle 29.5: Restless legs syndrome
MRCP revision battle 29.6: Histocytosis X
MRCP revision battle 29.7: Bartter's Syndrome
MRCP revision battle 29.8: Gitelman Syndrome
MRCP revision battle 29.9: Liddle's Syndrome




MRCP revision battle 29.1: Hypoglycaemia


Hypoglycaemia is defined as plasma glucose <3mmol/l.


In general in diabetics autonomic symptoms of hypoglycaemia (sweating, anxiety, tremor, palpitations) occur below 3.5mmol and neurological symptoms (confusion, drowsiness, seizures, coma) occur below 2.5mmol.

If a diabetic has frequent hypos they may become 'insensitive' and no longer experience symptoms before becoming unresponsive.  Symptoms may be 'restored' by carefully avoiding hypos for 3 months.


Causes of hypoglycaemia are easy to remember as it "IS PLAIN" to see...

• Insulin
• Sulphonyureas/other drugs
• Pituitary insufficiency
• Liver failure
• Addisons disease or alcohol
• Insulinoma
• Neoplasms eg retroperitoneal fibrosarcomas than secrete IGF

Take bloods for glucose, insulin, c-peptide and plasma ketones.
Normal/high insulin, no ketones: insulinoma, drugs
Insulin low, no ketones: non-pancreatic neoplasm
Insulin low, ketones high: alcohol, addissons, pituitary insufficiency.





Post-pradial hypoglycaemia can occur post-gastrectomy





Whipples Triad is a set of criteria which if fulfilled suggest a patient's symptoms are due to hypoglycaemia:

• symptoms suggestive of hypoglycaemia
• BM < or equal to 2.5
• symptoms relieved by food.

Treatment

I'm sure this is all old-hat to you all... get the pt to eat if they can, 1mg IM glucagon if they can't and no IV access (remember glucagon effects only last for 20 mins and may not work at all in alcoholics) and if IV is an option the 50mls of 50% glucose or the more modern 200mls of 10% (less abrasive to the veins)


Now for some TED time...

MRCP revision battle 29.2: Thyroid eye disease

Thyroid eye disease, referred to by its friends as 'TED', can occur in people who are hyperthyroid, hypothyroid or euthyroid.


Thyrotoxicosis from any cause can cause lid lag and lid retraction.


However, only Graves disease causes:

• periorbital oedema
• conjunctivial injection
• proptosis/exophthalmos
• opthalmoplegia/diplopia
• papilloedema

(as an aside, I've always been mystified by the difference between proptosis and exophthalmos.  Unfortunately it appears I'm not the only one as some sources suggest the difference is related to the degree of protrusion whilst others say exophthalmos is used if the aetiology is endocrine and proptosis is used if the aetiology is not endocrine...)



25-50% of patients with Grave's disease have TED.


Risk of TED is increased in smokers.


The danger of TED is optic nerve compression.  Symptoms/signs of optic nerve compression include:

• blurred vision/decrease VA
• decreased colour vision
• a relative afferent papillary defect

Treatment for TED is topical lubricants, steroids if severe and possibly even surgery.



Now for a horrid battle with hyperlipidaemia...

MRCP revision battle 29.3: Hyperlipidaemia

This battle is quickly going to get complex and aims only to be an MRCP-focused overview rather than a comprehensive discussion.  It is divided into 5 stages:

1. The basics
2. Hypercholesterolaemia
3. HDL - the good cholesterol
4. Hypertriglyceridaemia
5. Mixed

1. The Basics

Hyperlipidaemia = raised lipids.  Lipids come in 4 main 'flavours':

1. chylomicrons = carry triglyceride
2. LDL = mainly cholesterol (50%, 10% TG) = the 'bad' flavour
3. HDL = mainly phospholipid = the 'good' flavour, carry cholesterol back to the liver
4. VLDL = mainly triglyceride (60%, 20% cholesterol)

Signs:

• corneal arcus = grey-white ring around cornea
• xanthelasma = yellow collection of cholesterol under skin
• xanthomata = 'lumps' of cholesterol
• eruptive xanthomata = small yellow-orange papules that appear all over body
• lipaemia retinalis = 'creamy' appearence of blood vessels on fundoscopy

So lets look first at cholesterol and hypercholesterolaemia.




2. Hypercholesterolamia

a. Familial

• LDL receptor dysfunction
• cholesterol 7.5-16
• raised LDL
• tendon xanthomata, corneal arcus and xanthelasma
• heterozygous prevalance 1/500 --> MI in 40s
• homozygous --> MI in 20s
• Polygenic hypercholesterolaemia
• cholesterol 6.5-9
• raised LDL
• xanthelasma and corneal arcus

 b. Acquired

• nephrotic syndrome
• renal transplant
• cholestasis
• hypothyroidism

3.  HDL

HDL is 'good' cholesterol

It is higher in:

• thin people
• exercise
• oestrogens
• alcohol
• low triglycerides

It is lower in:

• obesity
• sedentary states
• post-puberty males
• smoking

4. Hypertriglyceridaemia

a. Familial

• failure to metabolise chylomicrcons
• features include:
• eruptive xanthomata
• lipaemia retinalis
• retinal vein thrombosis
• pancreatitis
• hepatosplenomegaly

b. Secondary

• diabetes
• obestiy
• alcohol
• chronic renal failure
• liver disease
• drugs such as thiazides, beta blockers or oestrogens

5. Mixed hyperlipidaemia

• Look for palar xanthomas and tuberous xanthomas

After that wordy and depressing battle, lets move on to treatment of hyperlipidaemia...

MRCP revision battle 29.4: Lipid-lowering treatment

NICE recommends that all those with a 10 yr cardiovascular risk of >20% should be offered lipid-lowering therapy.

1st line: 40mg simvastatin
Measure LFTs when starting, at 3 months and at 12 months.


In primary prevention there is no 'target' cholesterol
In secondary prevention the target is less than 4mmol/l cholesterol and less than 2mmol/l LDL



If statins are not tolerated consider:

• fibrates
• ezetimibe
• nicotinic acid

Mechanisms of action


Statins are HMG CoA reductase inhibitors.  They therefore work by decreasing the production of cholesterol in the liver.  The decreased production of cholesterol in the liver also results in the liver absorbing and processing more LDL, hence further reducing cholesterol.


Grapefruit juice decreases the metabolism of statins.  Patients on statins are therefore advised to avoid grapefruit juice as it would increase the risk of the rare side effect of rhabdomyolysis



Ezetimibe works by preventing intestinal absorption of cholesterol.



Fibrates are PPAR alpha receptor agonists.  They therefore increase clearance of VLDL and remnant particles and decrease TG secreation.

Fibrates and statins tend not to be used together due to increased risk of rhabdomyolysis.



Nicotinic acid (=vitamin B3) blocks breakdown of fats in adipose tissue. 
It can cause facial flushing.

For the really keen:

NICE lipid modification guide

After those heavy-going battles lets tackle something light - restless legs syndrome...                             

MRCP revision battle 29.5: Restless legs syndrome

Restless legs syndrome, sometimes known as Ekbom's syndrome, is a condition in which a person has unpleasant sensations in their legs and a desire to move them.


Restless legs may be idiopathic or secondary to:

• pregnancy
• iron deficiency
• ureamia
• diabetes
• RA

1st line treatments are dopamine agonists such as pramipexole
2nd line treatments include benzodiazepines or gabapentin.



To keep the neurones jumping lets move on to a completely different topic again - histiocytosis X...

MRCP revision battle 29.6: Histiocytosis X

Histocytosis X, aka Langerhans-cell histiocytosis, is a group of disorders in which there is organ infiltration by granulomatous lesions containing clonally proliferated dendrintic (=Langerhams) cells.


The most commonly affected organs are lungs and bones.


Lung histiocytosis tends to affect young adults and is commonest in smokers.

The CXR shows multiple ring shadows with diffuse reticulo-nodular opacities affecting mainly the upper and mid zones.


Biopsy would show characteristic Birbeck granules.


Treatment is ?local excision, ?steroids.


Now onwards for a run of the last 3 short battles of the day, starting with Bartter's Syndrome...