MRCP revision battle 25.1: Neuroleptic Malignant Syndrome

Having been blessed by a set of on-calls with some nice interesting cases I'm full of enthusiasm for today's battles, so lets get on with it!


MRCP revision battle 25.1: Neuroleptic malignant syndrome
MRCP revision battle 25.2: Behcets disease
MRCP revision battle 25.3: Subarachnoid haemorrhage
MRCP revision battle 25.4: Normal pressure hydrocephalus
MRCP revision battle 25.5: Gas gangrene
MRCP revision battle 25.6: Methaemoglobinaemia
MRCP revision battle 25.7: The weeverfish




MRCP revision battle 25.1: Neuroleptic malignant syndrome


A nice straightfoward battle to begin with...


Neuroleptic malignant syndrome is a life-threatening condition associated with use of antipsychotic drugs.


Symptoms and signs include:

• hyperthermia
• rigidity/muscle cramps
• extrapyramidal signs
• autonomic dysfunction (labile BP, sweating, urinary incontinence
• confusion

Investigations show:

• raised CK
• raised WCC

Treatment is:

• cooling
• dantrolene (a muscle relaxant; note dantrolene is also used in malignant hyperthermia, which will be one of tomorrows battles)

Now on to a slightly less straightforward battle, Behcets disease...

MRCP revision battle 25.2: Behcets disease

Behcet's disease is a systemic vasculitis of unknown cause.


The classic triad of Behcet's disease is:

• oral ulcers
• genital ulcers
• anterior uveitus

which I remember as GOA, like the place in India.



Other possible features include:

• thrombophlebitis
• DVT
• erythema nodosum
• pathergy reaction (=needle prick leads to pustule formation)
• arthritis
• aseptic meningitis
• ataxia
• diarrhoea

Males are more commonly affected than females.
It is commonest in Turkey and Japan.
30% of patients have a positive family history.


HLA B5 is associated with anterior uveitis and HLA B12 is associated with recurrent ulceration.


Severe disease requires steroids/ciclosporin/azathioprine.


Next up - SAH...

MRCP revision battle 25.3: Subarachnoid haemorrhage

Subarachnoid haemorrhage is bleeding into the space between the subarachnoid membrane and the pia mater.

It accounts for 5-10% of all strokes.


Causes:

• ruptured berry aneurysm (80%)
• malformations (15%)
• post trauma

Common sites of berry aneurysms are:

• junction of the posterior communicating artery with the internal carotid
• junction of the anterior communicating artery with the anterior cerebral artery
• the bifurcation of the middle cerebral artery

If (like me) your anatomy of the circle of willis is a little rusty the wiki commons image below might help refresh your memory:

15% of berry aneurysms are multiple.




Subarachnoid haemorrhages are associated with:

• polycystic kidneys
• coarctation of the aorta
• Ehlers-Danlos syndrome
• PAN

Classical presentation is a thunderclap occipital headache "as if kicked in head" with vomiting and neck stiffness.
Around 6% of patients will have had a sentinel headache before.



Investigation is:

• CT - >90% of bleeds detected
• LP - done >12hrs after onset looking for xanthochromia

Management:

• neurosurgical referral
• prompt angiography if surgery likely
• nimodipine

On to another neuro topic - normal pressure hydrocephalus

MRCP revision battle 25.4: Normal pressure hydrocephalus

Normal pressure hydrocephalus is a triad of:

1. dementia
2. gait abnormality
3. urinary incontinence

(remember as DUG!)


It is caused by a defect in the absorption of CSF.
Causes include: meningitis, head injury, subarachnoid haemorrhage.


Note that there is NO headache and NO papilloedema.


Investigations:

• CT head (predictably) - enlarged ventricles
• large volume lumbar puncture - ? high opening pressure, ? improvement of symptoms
• lumbar infusion test

Treatment is a shunt.



Next up... gas gangrene!

MRCP revision battle 25.5: Gas gangrene

Gas gangrene is a life threatening bacterial infection.

It is characterised by muscle necrosis, gas production and sepsis.

A typical appearance is shown below:

                                       From Wiki Commons, taken by Engelbert Schröpfer, Stephan Rauthe and Thomas Meyer.






Most cases are caused by trauma innoculation with bacteria, for example a farmer standing on a pitchfork.
Very rarely it may occur spontaneously, for example in the context of neutropenia.


The commonest causative organism is clostridium perfringens.


Management is:

• urgent surgical debridement
• IV Abx 
• hyperbaric oxygen if available

Next up - methaemoglobinaemia

MRCP revision battle 25.6: Methaemoglobinaemia

Methaemoglobin (MetHb) is formed when the iron in haemoglobin is oxidised from the ferrous state (Fe2+) to the ferric state (Fe3+) 


Methaemoglobinaemia means raised MetHb levels, and as MetHb has a far higher affinity for oxygen than normal haemoglobin this results in tissue hypoxia as the oxygen being carried in the blood is not given up to the tissues.



Clinical features depend on the % of MetHb:

• 15-20% - cyanosis
• 20-45% - impaired consciousness
• >55% - seizures, arrhythmias, coma
• >70% - lethal

Pulse oximetry will show low oxygen sats, as will the printout from blood gas analysis - but the PaO2 will be high.



Causes of methaemoglobinaemia:

• congenital
• pyruvate kinase deficiency
• G6PD deficiency
• abnormal haemoglobin - HbH or HbM
• diaphorase 1 deficiency
• acquired - accelerated rate of oxidised formation due to meds
• antibiotics - sulphonamides, trimethoprim, dapsone
• drugs used in anaesthetics - lidocaine, procaine
• others -primaquine

Management:

• 1% solution of methylene blue
• hyperbaric oxygen
• exchange transfusion
• dialysis
• asorbic acid in patients with G6PD deficiency

So to the final battle of the day - weeverfish!

MRCP revision battle 25.7: The weeverfish

Just very briefly...

The weeverfish (AKA trachinus vipera) is found in shallow waters around the coast of the UK.

It is small and sandy-coloured, with sharp dorsal spines.


If you are unfortunate enough to stand on it you will get intense pain.

Happily the toxin produced by the weeverfish is denatured above 40C - so dunk the foot in hot water and the pain should stop.


On that most random of MRCP revision notes, lets end for the day!

MRCP questions: War 24

 I now have a co-conspirator for MRCP revision on the go... lets call her Dr Biscuit and she is now writing all the wars!  How hard they are will probably reflect how bad her day has been... good luck!


As with previous 'wars' after 'battles' these are just a few quick questions to see if your brain cells have retained the information provided in battles 24:1 to 24:6.

The answers are available here


Question 1:
You are referred a patient who was diagnosed with Primary Biliary Cirrhosis 2 years ago. Name 3 signs you might find on clinical examination?

Question 2:
What blood test would you do to confirm the diagnosis of PBC?


Question 3:
A 22 year old female patient presents with DIC and hepatosplenomegaly.  Blood film shows cells which are strongly sudan black/peroxidase positive. What is the diagnosis and what is the gene translocation?



Question 4:
Name 3 drugs which can be used to treat AML?


Question 5:
Name 3 conditions associated with angioid retinal streaks?


Question 6:
List 3 drugs/groups of drugs which can cause SIADH?


Question 7:
Your patient is hyponatraemic with a sodium of 120.  On examination they appear clinically dehydrated. What investigation would you request next to help you elucidate the cause of the hyponatraemia?


Question 8:
Your patient is hyponatraemic with a sodium of 118.  Name four signs or symptoms they might display?


Question 9:
A patient is admitted with confusion. You are unable to obtain a history from her family but she takes no medications.  Her sodium is 119.  On examination she appears euvolaemic.  The admitting doctor has sent a urine sample which shows a urinary na of 34, and urine osmolality of 750. What is the likely diagnosis?


Question 10:
What are the 2 main effects of ADH?



The answers are available here

MRCP revision battle 24.1: Primary biliary cirrhosis

All this working and revising is leaving me with little internet-publishable material to put into my daily intros.  Looking for inspiration I ended up stumbling accross an utterly brilliant set of articles written back in the early 2000's by a (then) junior doctor called Michael Foxton in the Guardian.  Hopefully this link will take you to a list of his articles to soothe you after some revision.... but I warn you not to start looking before you've finished revising for the day because otherwise there is a real danger you will get no revision done!!



So today's battles are:

MRCP revision battle 24.1: Primary biliary cirrhosis
MRCP revision battle 24.2: Acute Myeloid Leukaemia
MRCP revision battle 24.3: Acute Promyelocytic Leukaemia
MRCP revision battle 24.4: Angioid retinal streaks
MRCP revision battle 24.5: SIADH
MRCP revision battle 24.6: Hyponatraemia
MRCP revision battle 24.7: Neutropenia and neutrophillia




MRCP revision battle 24.1: Primary biliary cirrhosis



I've never bonded well with this topic so this battle is a personal Waterloo for me...


Primary biliary cirrhosis is thought to be an autoimmune condition in which the interlobular bile ducts are damanged by chronic granulomatous inflammation. 


The result of this is:

• progressive cholestasis
• cirrhosis
• portal hypertension

Females are more affected than males (9:1) and it tends to present in middle age.

It is associated with many other autoimmune conditions, including sjogrens, RA, systemic sclerosis, thyroid disease...


Primary biliary cirrhosis is often found incidentally by a raised alk phos on LFTs.Initially other LFTs may be normal but as the disease progresses bilirubin rises and PT may increase.


Associated signs (in late disease) include:

• jaundice
• xanthelasma
• hepatosplenomegaly
• clubbing

Complications include:

• osteoporosis
• portal hypertension
• variceal haemorrhage

Diagnosis includes antibodies:

• AMA M2 is highly specific and is positive in 98% of cases
• SMA is positive in 30%
• raised IgM

Treatment is:

• cholestyramine for itching
• osteoporosis prophylaxis
• transplant

Once jaundice develops, without transplant the survival is < 2yrs.


On to AML...

MRCP revision battle 24.2: AML

Acute myeloid leukaemia is cancer of the myeloid line of blood cells.
Myeloid cells are essentially all blood cells that are not leukocytes.


It is the commonest leukaemia in adults.


Presentation may be by:

• complications of marrow failure
• anaemia
• infection
• bleeding
• evidence of marrow infiltration
• hepato/splenomegaly
• gum hypertrophy

CNS involvement is rare in AML (contrasted with ALL, where it is common)


Diagnosis is by bone marrow biopsy.
Immunophenotyping/cytogenetic analysis is important to guide treatment and indicate prognosis.


The key feature on microsopy is the auer rod - note the small rod in the cytoplasm of the central cell:

 

Classification was traditionally done by the FAB (French-American-British) classification, which ran from M0 to M7.  The important random facts I remember from this is that M2 is associated with t(8;21) and M3 (aka acute promyelocytic leukaemia, the topic of the next battle) is associated with t(15;17).  Both of these translocations are associated with a good prognosis.

Now the WHO classification is more commonly used.  It is rather complex and includes catagories such as 'AML with characteristic abnormalities' and 'AML therapy-related'  If you are interested the further reading link at the bottom will tell you more.

Treatment is supportive care and intensive chemotherapy, usually with cytosine arabinoside and daunorubicin, or bone marrow transplant.

Survival with no treatment is around 2 months; with chemo there is around 20% 3 yr survival.

For the really keen:

Further information on WHO classification of AML

Now lets briefly look at acute promyelocytic leukaemia...

MRCP revision battle 24.3: Acute Promyelocytic Leukaemia

Acute Promyelocytic Leukaemia is the M3 subtype of AML.

It is associated with the t(15;17) translocation and the RARA gene.


On microscopy you look for faggots (=collections of auer rods):

 

The cells are strongly sudan black/peroxidase positive.

Acute promyelocytic leukaemia tends to present in young adults (average approx 25 yrs) and the presentation is often DIC.

Despite this sounding bad, acute promyelocytic leukaemia actually has a good prognosis.

Remission can be induce with all-trans retinoic acid.

Thats enough heavy-going haematology for one day... lets move on to angioid retinal streaks...

MRCP revision battle 24.4: Angioid retinal streaks

Angioid retinal streaks are caused by breaks in Bruch's membrane. 


They look like dark red lines under the retina - almost like blood vessels.  I'd recommend using google to search for a selection of images to look at.


They are associated with SLAPPERS:

• Sickle cell disease
• Lead poisoning
• Acromegaly
• Pagets disease
• Pseudoxanthoma elasticum
• Ehlers-Danlos
• Raised calicum/phosphate
• Short people

 Onwards to SIADH...

MRCP revision battle 24.5: SIADH

SIADH = syndrome of inappropriate antidiuretic hormone secretion is a condition whose name really says it all: it is ADH being produced and released when it shouldn't be.


Quick bit of physiological background:

• ADH is made in the magnocellular neurones in the supraoptic and paraventricular nuclei of the hypothalmus
• ADH is stored in the posterior pituitary
• it is released in response to raised plasma osmolality (osmoreceptors in hypothalamus) or decreased volume (baroreceptors in carotids, atria)
• its effect is to increase the insertion of aquaporin 2 channels in the collecting ducts of the kidney, hence increasing water reabsorption.
• it also increases peripheral vascular resistance

SIADH is diagnosed in the presence of:

• concentrated urine ( sodium >20mmol/l and osmolality >500mosmol/kg) AND
• hyponaturaemia (<125) or low plasma osmolality (<260mosmol/kg) AND
• the absence of hypovolaemia, oedema or diuretics.

Causes of SIADH include:

• malignancy: small cell lung cancer, pancreas, prostate, lymphoma
• lung pathology: TB, pneumonia, aspergillosis
• CNS pathology: injury, GBS, fits, subarachnoid/subdural haemorrhage, abscess, stroke
• metabolic: porphyria
• drugs: opiates, carbamazepine, SSRIs, TCA

So lets now finish todays battles by widening this topic out to hyponatraemia...

MRCP revision battle 24.6: Hyponatraemia

Hyponatraemia is low blood sodium.  The effect of this will depend on how low and for how long.

Possible signs and symptoms include:

• confusion
• seizures
• hypertension
• cardiac failrue
• anorexia
• nausea
• muscle weakness
• oedema

(=CASH MON)


My personal way of dealing with hyponatraemia is to begin by asking 2 cynical questions:

1. is it actually just dilutional? - ?hyperglycaemia 
2. is it actually just pseudo? - ?high protein ?high triglycerides

Once I've got negatives to my cynicism, I move on to ask:

1. are they dehydrated or not?

The divisions from this question onwards are summarised in the diagram below:

If the low sodium is chronic, you treat by:

• treating cause
• giving cautious N.saline if dehydrated
• fluid restricting if not dehydrated.

Occasionally demeclocycline might be needed; this is an antibiotic which has the side effect of inducing nephrogenic diabetes inspidus and hence helps treat SIADH.


Now on to neutrophils...

MRCP revision battle 24.7: Neutropenia and neutrophilia

Your humble neutrophil makes up 40-75% of your white blood cells.
It lives for a mere 5 days.
It migrates towards the 'bad guys' by following the signals of substances including IL-8.
It valiantly phagocytoses bacteria.

MRCP examiners enjoy asking questions about low and high levels of neutrophils...


Neutropenia = low neutrophil count

Causes:

• viral infection
• severe sepsis
• bone marrow failure
• neutrophil antibodies (eg SLE, haemolytic anaemia)
• drugs - chemotherapy, carbimazole

Neutrophilia = raised neutrophil count.

Causes:

• bacterial infection
• MI
• steroids
• pregnancy
• uraemia
• acidosis
• gout
• myeloproliferative disorders

That's all the hard work done for today; for some light relief click this link

MRCP revision battle 23.1: Henoch Schonlein purpura

No energy for an interesting introduction today... lets dive straight into the battles...



MRCP revision battle 23.1: Henoch Schonlein purpura
MRCP revision battle 23.2: Parinaud's syndrome
MRCP revision battle 23.3: Polymyositis and Dermatomyositis
MRCP revision battle 23.4: Trichomonas vaginalis
MRCP revision battle 23.5: Atrial septal defects
MRCP revision battle 23.6: Pyoderma gangrenosum



MRCP revision battle 23.1: Henoch Schonlein purpura


Henoch Schonlein Purpura (HSP) is a an IgA mediated small vessel vasculitis.

Classically it affects mainly children post infection.


Features include:

• symmetrical macular rash over buttocks and extensor surfaces of legs
• abdominal pain +/- blood diarrhoea
• arthralgia

Complications of HSP include:

• renal failure (look for microhaematuria)
• intussusception

Management is supportive.


Now for a very quick battle, Parinaud's Syndrome...

MRCP revision battle 23.2: Parinaud's syndrome

Parinaud's syndrome refers to the combination of:

• upward gaze palsy
• pseudo Argyll-Robertson pupils

Causes include:

• hydrocephalus
• pineal tumours
• stroke
• multiple sclerosis

Onwards to the longer 'buy-one-get-one-free' battle of dermatomyositis and polymyositis...

MRCP revision battle 23.3: Polymyositis and Dermatomyositis

Polymyositis is an idiopathic inflammatory disorder of skeletal muscle.  When it is associated with cutaneous lesions it is dermatomyositis.


Features:

• progressive proximal muscle weakness
• dysphagia
• interstitial lung disease
• oesophageal dysfunction
• weight loss 
• fever
• myocarditis
• arthralgia

To try and remember this list I think of the condition starting in the proximal muscles of the arm then creeping to the joint (causing arthralgia) and onwards to the oesophagus, causing dysphagia and oesphageal dysfunction.  I then imagine it seeping into the lungs (interstitial lung disease) and then onwards into the heart (myocarditis).



Skin signs include:

• heliotrope (liliac-purple) rash around eyelids/cheeks
• macular rash over back and shoulders (=shawl sign)
• Gottrons papules = scaly plaques on MCP/PIP joints
• Gottrons sign = erythema over knees/elbows
• periungal telangectasia
• nail fold infarcts
• photosensitivity

There is a higher prevalence of malignancy with dermatomyositis.


Investigations show:

• raised CK/AST/LDH
• abnormal EMG - shows fibrillation potentials
• anti-Jo antibodies associated with a systemic form of disease

Treatment is:

• prednisolone
• methotrexate
• screen for maligancy.

NB: juvenile dermatomyositis is different - it is more aggressive and includes a vasculitis and ectopic calcification.



Now onwards for our first expedition into the world of sexually transmitted diseases...

MRCP revision battle 23.4: Trichomonas vaginalis

Trichomonas vaginalis is an anaerobic protozoan that is transmitted sexually.

It needs an alkaline pH to thrive.


It can cause:

• thin, grey, fishy discharge
• itchiness
• dysparenia
• dysuria

As it inflames the endothelium it increases an individual's susceptibility to other sexually transmitted infections.


Treatment is with metronidazole.



Now on to atrial septal defects...

MRCP revision battle 23.5: Atrial septal defects

Atrial septal defects may present as:

• dyspnoea on exertion
• finding after AF diagnosed
• finding after CVA
• finding after heart failure

Clinical signs include:

• fixed splitting S2
• ejection systolic murmur
• left parasternal heave

A cardiac echo may show paradoxical ventricular septal motion due to right sided overload.



There are 3 main atrial septal defects to be aware of:


1: Ostium secundum defect

• Ostium secundum defects account for 70% of atrial septal defects
• caused by an enlarged foramen ovale
• ECG shows RBBB with right axis deviation and a long PR
• 10-20% of cases will be associated with mitral valve prolapse
• it tends to present in adulthood

2: Ostium primum defect

• ostium primum defects account for 15% of atrial septal defects
• ECG shows RBBB with left axis deviation and a long PR
• it tends to present earlier, in childhood
• it is associated with Downs, Klinefelters and Noonans
• some feel it should be classified as a atrioventricular septal defect as it is so low down in the atria, on the endocardial cushions
• often associated with TR/MR.

3: Sinus venous atrial septal defect

• up to 15% of cases

Treatment is closure.



A very small atrial septal defect is patent foramen ovale.  This is different from the others as as it is so small it does not allow equilisation of atrial pressures.  It occurs in 25% of the population and can allow paradoxical emboli (see below) and is associated with migraine.



Complications of ASDs include:

• Eisenmengers Syndrome
• left-to-right shunt causes increased blood flow through pulmonary vasculature and so pulmonary hypertension, which increases the pressure in the right side of the heart leading to reversal of the shun to right-to-left = eisenmnegers syndrome.
• paradoxical emboli 
• venous emboli ending up in arterial rather than venous system
• --> strokes, intestinal infarcts, splenic infarcts 
• ? migraines - controversial area of research - google if you are interested.

Finally for ASDs a brief eponymous syndrome that occasionally appears in MRCP answer options: Holt-Oram.  Holt Oram is an inherited condition characterised by abnormalities of the heart and upper limb.  It is inherited in an autosomal dominant manner with incomplete penetrance.

Now skip straight to last battle of the day