Block 1 Flashcards
Case-control study
Compares a group with a disease to a group without, looking at past exposure to a possible causal agent for the condition
Observational and prospective. Two (or more) are selected according to their exposure to a particular agent (e.g. medicine, toxin) and followed up to see how many develop a disease or other outcome.
The usual outcome measure is RR
Examples include Framingham Heart Study
Cohort Study
Observational and retrospective. Patients with a particular condition (cases) are identified and matched with controls. Data is then collected on past exposure to a possible causal agent for the condition.
The usual outcome measure is the odds ratio.
Inexpensive, produce quick results
Useful for studying rare conditions
Prone to confounding
Case-control study
Provide a ‘snapshot’, sometimes called prevalence studies
Provide weak evidence of cause and effect
Cross-sectional survey
A 25-year-old woman presents with recurrent attacks of ‘dizziness’. These attacks typically last around 30-60 minutes and occur every few days or so. During an attack ‘the room seems to be spinning’ and the patient often feels sick. These episodes are often accompanied by a ‘roaring’ sensation in the left ear. Otoscopy is normal but Weber’s test localises to the right ear. What is the most likely diagnosis?
Acoustic neuroma
Vestibular neuritis
Benign paroxysmal positional vertigo
Multiple sclerosis
Meniere’s disease
There is a suggestion of SNHL in the left ear as Weber’s localises to the right.
Along with transient vertigo and aural fullness Meniere’s is the most likely diagnosis
recurrent episodes of vertigo, tinnitus and hearing loss (sensorineural). Vertigo is usually the prominent symptom
a sensation of aural fullness or pressure is now recognised as being common
other features include nystagmus and a positive Romberg test
episodes last minutes to hours
typically symptoms are unilateral but bilateral symptoms may develop after a number of years
Menier’es disease
Natural Hx of Meniere’s
Symptoms resolve in the majority after 5-10 years.
Majority of patients will be left with a degree of hearing loss.
Mx of acute attacks of Meniere’s?
Buccal or IM prochlorperazine
Prevention of attacks in Meniere;s?
Betahistine
Vestibular rehabilitation exercises
Which part of the jugular venous waveform is associated with the opening of the tricuspid valve?
x descent
v wave
a wave
c wave
y descent
JVP: y descent = opening of tricuspid valve
a-wave of JVP
Atrial contraction
Large if raised atrial pressure e.g. TS or PS
Absent if in AF
Cannon a-waves
Caused by atrial contractions against a closed tricuspid valve
May be sene in complete heart block, VT/ectopics, nodal rhythmn, single chamber ventricular pacing
c-wave
Closure of the tricuspid valve
Not normally visible
V wave
Due to passive filling of blood into the atrium against a closed tricuspid valve
Giant v waves in TR
x-descent
Fall in atrial pressure during ventricular systole
y-descent
Opening of tricuspid valve
Each one of the following is associated with ataxic telangiectasia, except:
Telangiectasia
Cerebellar ataxia
Autosomal dominant inheritance
Recurrent chest infections
Increased risk of malignancy
AD inheritance
It is an autosomal recessive disorder
Pathology of ataxic telangiectasis
AR disorder caused by a defect in the ATM gene which encodes for a DNA repair enzym.e
It is one of the inherited combined immunodeficiency disorders, typically presenting in early childhood with abnormal movements.
Features of ataxic telangiectasis?
Cerebellar ataxia
Telangiectasis
IgA deficiency-> recurrent chest infections
10% risk of malignancy- lymphoma, leukaemia and non-lymphoid tumours
Onset 1-5years
Features of Friedrich’s ataxia?
Trinucleotide repeat disorder (but no anticipation)
Kyphoscoliosis
Optic atrophy
HOCM
DM
Onset 10-15 years
Which one of the following causes of primary immunodeficiency is a T-cell disorder?
Chediak-Higashi syndrome
Chronic granulomatous disease
Common variable immunodeficiency
DiGeorge syndrome
Wiskott-Aldrich syndrome
DiGeorge syndrome is a primary immunodeficiency disorder caused by T-cell deficiency and dysfunction. It is an example of a microdeletion syndrome. Patients are consequently at increased risk of viral and fungal infections.
Parthology of Di George
Primary immunodeficiency disorder caused by T-cell deficiency and dysfunction due to microdeletion of 22q11.2.
Clinical features of Di Geoge syndrome
CATCH 22
Cardiac abnormalities
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcaemia/hypoparathyroidism
22 chromosome microdeletion
A 33-year-old Indian man presented with a 5-day history of fevers, vomiting and dizziness. He had recently come back from a trip to Kerala and had been treated with a two-week course of clarithromycin for a bout of prolonged severe sinusitis by his GP. This was due to the fact that he had been suffering from severe frontal headaches, difficulty sleeping and periorbital swelling. He has a background of tuberculosis (TB) and is currently on treatment with rifampicin and isoniazid.
On examination, there was some slurring dysarthria and mild coarse nystagmus to the left. His observation shows a temperate of 38.3ºC, pulse 93 beats per minute, blood pressure 120/80mmHg and oxygen saturation 93% on room air.
What is the most likely diagnosis?
TB meningitis
Cerebellar metastases
Cerebellar haemorrhage
Cerebellar abscess
Chronic sinusitis
Cerebellar abscesses are most commonly caused by otogenic diseases like mastoiditis and sinusitis infections
Brain abscesses are focal areas of intracerebral pus collection which occur due to a number of causes. In particular, cerebellar abscesses most commonly occur due to infections such as mastoiditis and sinusitis infections.
Cerebellar haemorrhage is a more acute vascular event which would have a quicker onset and likely present with stronger neurological signs with sudden onset headache, dizziness, vomiting, vertigo, truncal ataxia and impairment of consciousness.
Chronic sinusitis is referred to when the cavities around nasal passages - known as sinuses - remain inflamed and swollen for at least 12 weeks, in spite of various treatment attempts.
TB meningitis would present with fever and chills, neck stiffness, photophobia associated with mental changes.
Cerebellar metastases would present with headaches (the most common symptom of brain metastases), nausea, vomiting, difficulty walking, seizures with speech disturbance.
A 49-year-old female is referred to the gastroenterology out-patient clinic with a 3 month history of epigastric pain and diarrhoea. Her GP initially prescribed lansoprazole 30mg od but this didn’t alleviate her symptoms. The only past medical history of note is hyperparathyroidism.
Endoscopy revealed multiple duodenal ulcerations. What is the likely diagnosis?
Multiple endocrine neoplasia type II a
Coeliac disease
Multiple endocrine neoplasia type I
Autoimmune polyendocrinopathy syndrome
Crohn’s disease
Zollinger-Ellison syndrome typically presents with multiple gastroduodenal ulcers causing abdominal pain and diarrhoea. High-dose proton pump inhibitors are needed to control the symptoms. Around a third of patients may have multiple endocrine neoplasia type I (MEN-I), explaining the hyperparathyroidism in this patient.
MEN-I
parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
pituitary (70%)
pancreas (50%, e.g. Insulinoma, gastrinoma)
also: adrenal and thyroid
Diagnosis of ZE syndrome
Fasting gastrin levels
Secretin stimulation test
What is the underlying problem in methaemoglobinaemia?
The oxidation of Fe2+ in haemoglobin to Fe3+
The reduction of Fe2+ in haemoglobin to Fe+
The oxidation of Fe3+ in haemoglobin to Fe2+
The reduction of Fe2+ in haemoglobin to Fe3+
The reduction of Fe3+ in haemoglobin to Fe2+
Methaemoglobinaemia = oxidation of Fe2+ in haemoglobin to Fe3+
Methaemoglobinaemia
Describes Hb which has been oxidised from Fe2+ to Fe3+.
This is normally regulated by NADH methaemoglobin reductase which transfers electrons from NADH to methaemoglobin.
In methemoglobinaemia there is tissue hypoxia as Fe3+ cannot bind oxygen, moving the oxidation dissociation curve to the left.
Causes of methaemoglobinaemia
Congenital:
Hb chain variants- HbM, HbH
NADH methaemoglobin reductase deficiency
Acquired:
Drugs- sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine
Aniline dyes
Chocolate cyanosis
Dyspnoea, anxiety, headache
Severe: acidosis, arrhythmias, seizures, coma.
Normal pO2 but decreased O2 saturation
?Methaemoglobinaemia
Mx of methaemoglobinaemia
NADH-methaemoglobinaemia reductase deficiency- ascorbic acid
IV methylthionium chloride (methylene blue) if acquired.
An 18-year-old male is admitted to hospital for haemoptysis. He mentioned that his urine has recently become brown in colour. On examination, his blood pressure is noted to be 170/110. A kidney biopsy is stained positive for autoantibodies confirming a diagnosis of Goodpasture’s syndrome. Which type of collagen does this patient produce autoantibodies against?
Collagen type 1
Collagen type 2
Collagen type 3
Collagen type 4
Collagen type 5
Collagen IV is defective in Goodpasture’s syndrome.
Ehlers-Danlos syndrome is primarily caused by a genetic defect in collagen type III. Collagen Type V is also affected in a less common variant of Ehlers-Danlos syndrome. Collagen type I is defective in osteogenesis imperfecta.
Collagen 1 deficiency
Osteogenesis imperfecta
Associations of collagen IV defect
Alport
Goodpasture’s
Collagen V abnormality
Classical Ehlers-Danlos
Structure of Collagen Type 1
3 polypeptides in an alpha helix.
Numerous H bonds
Collagen 1 most common subtype (90%)
VItamin C involved in establishing cross links
Synthesised by fibroblasts
A middle aged man presents with pyrexia and cough. Chest X ray demonstrates a left lower lobe pneumonia. He is seen in the emergency department with a blood pressure of 83/60mmHg and a heart rate of 112/min. He is prescribed broad spectrum antibiotics and intravenous fluid.
Which of the following best describes the mechanism of the bodies response to a decrease in blood pressure?
Decreased heart rate and vasoconstriction
Decreased epithelial sodium channels in distal convoluted tubule
Increased bradykinin
Insertion of AQP-2 channels in collecting ducts
Insertion of AQP-2 channels in thick ascending loop of Henle
In response to low blood pressure, there are a variety of physiological responses. Including the renin-angiotensin aldosterone system (RAAS). Bradykinin is a potent vasodilator which is broken down by angiotensin-converting enzyme (ACE).
RAAS activation leads to increased aldosterone which leads to increased epithelial sodium channels (ENAC) to increase sodium reabsorption.
Another response to low blood pressure is increased anti-diuretic hormone with increases insertion of AQP-2 channels in the collecting duct to increase water reabsorptio
Which one of the following is least likely to cause a raised protein level in the cerebrospinal fluid?
Tuberculous meningitis
Guillain-Barre syndrome
Fungal meningitis
Froin’s syndrome
Systemic lupus erythematous
SLE
The following conditions are associated with raised protein levels
Guillain-Barre syndrome
tuberculous, fungal and bacterial meningitis
Froin’s syndrome*
viral encephalitis
*describes an increase in CSF protein below a spinal canal blockage (e.g. tumour, disc, infection
A 37-year-old female patient is brought into the emergency department with a 5-day history of altered personality, visual and auditory hallucinations. On palpation of the abdomen, a mass is felt in the left iliac fossa. Ultrasound abdomen suggests a left ovarian tumour. Her basic observations are as follows:
Oxygen saturation99% on air
Heart rate98 beats/minute
Respiratory rate28 breaths/minute
Temperature37.9 °C
What is the most likely diagnosis?
Meningitis
Anti-NMDA receptor encephalitis
Rabies
Japanese encephalitis
Mania
Anti-NMDA receptor encephalitis is a paraneoplastic syndrome which presents with prominent psychiatric features. In this case, it is likely caused by an ovarian tumour.
Meningitis does not usually present with prominent psychiatric features
Rabies can present with psychiatric symptoms, but it usually presents with hypersalivation of hydrophobia which is not the feature here.
Japanese encephalitis is less likely with no clear travel history given and does not usually present with such prominent psychiatric symptoms.
The patient presents with symptoms of psychosis but no suggestion of mood disturbance hence mania is unlikely. Given the finding of an ovarian tumour and abnormality in her vital signs, an organic illness needs to be ruled out before psychiatric illness can be diagnosed.
Which one of the following is least recognised as a cause of autonomic neuropathy
Guillain-Barre syndrome
New variant CJD
Diabetes
Parkinson’s
HIV
New vCJD
Clinical features of autonomic neuropathy?
Impotence, inability to sweat, postural hypotension (drop of 30/15)
Loss of decrease n heart rate following deep breathing.
Dilatation of pupils following adrenaline instillation
Causes of autonomic neuropathy
DM
GBS
MSA
PD
Infections: HIV, Chaga’s, Shy-Drager
Antihypertensive, TCAs
Craniopharyngioma
Which of the following drugs is least likely to cause peripheral neuropathy?
Amiodarone
Vincristine
Trimethoprim
Isoniazid
Nitrofurantoin
Trimethoprim is not listed in the BNF as causing peripheral neuropathy
List drugs causing a peripheral neuropathy
Drugs causing a peripheral neuropathy
amiodarone
isoniazid
vincristine
nitrofurantoin
metronidazole
A 49-year-old man presents to the Emergency Department complaining of visual disturbance. Examination reveals a right incongruous homonymous hemianopia. Where is the lesion most likely to be?
Left optic tract
Left optic radiation
Right optic tract
Right optic radiation
Optic chiasm
Left optic tract
What is a congruous visual field defect?
Means compete or symmetrical visual filed loss.
An incongruous defect is incomplete or asymmetric
A man is recovering after having an operation to remove a meningioma in his left temporal lobe. What sort of visual field defect is he at risk of having following the procedure?
Visual field defects:
left homonymous hemianopia means visual field defect to the left, i.e. lesion of right optic tract
homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)
incongruous defects = optic tract lesion; congruous defects= optic radiation lesion or occipital cortex
Which one of the following statements regarding absence seizures is incorrect?
Typical age of onset of 3-10 years old
Sodium valproate and ethosuximide are first-line treatments
Seizures may be provoked by a child holding their breath
There is a good prognosis
Characteristic EEG changes are seen
Seizures are characteristically provoked by hyperventilation
Mx of absence seizures
VPA and ethosuximide are the first line
A 32-year-old woman is brought into the emergency department by ambulance with following an episode in of vertigo, diplopia and dysarthria, after which she became drowsy and responsive to pain only. Her symptoms came on over ten minutes and lasted for approximately one hour. Her initial symptoms have now fully resolved, but she feels nauseous. Neurological examination is unremarkable. She has a past medical history of migraine. She takes the progesterone-only contraceptive pill, but no other medications.
What is the most likely diagnosis?
Focal aware seizure
Focal impaired awareness seizure
Migraine with brainstem aura
Transient ischaemic attack
Multiple sclerosis
Migraine is common, with a prevalence of approximately 10% of the population. Therefore, even rare presentation of migraine may occur more commonly than common presentations of rarer conditions. This is migraine with brainstem aura (basilar-type migraine, or Bickerstaff’s Syndrome). The gradual onset over ten minutes, and step-wise progression of symptoms point more towards migraine than an ischaemic event. A reminder that it is possible for migraine aura to occur without the subsequent headache, as in this case. New-onset seizures would be less likely than an atypical presentation of known migraine. Multiple sclerosis would not present like this.
Clinical featuers of migraine
Primary headache
Characterised by a severe unilateral, throbbing headache
Associated with nausea, photophobia and phonophobia
Lasting up to 72h
Aura present in 1/3rd
Typical aura are visual, progressive and characterised by transient hemianopic disturbance or spreading scintillating scotoma
Which one of the following is least associated with Miller-Fisher syndrome?
Anti-GQ1b antibodies
Areflexia
Ataxia
Postural hypotension
Ophthalmoplegia
Postural hypotension due to autonomic involvement is not a feature of Miller Fisher syndrome, but may be seen in Guillain-Barre syndrome
Auto-antiboides in GBS
Anti-ganglioside (anti-GM1) seen in 25%
Auto-antibodies in MFS
Anti-GQ1b present in 90%
Clinical features of MFS
Associated with ophthalmoplegia, areflexia and ataxia with the eye muscles affefted first.
Presents as a descending paralysis
A 45-year-old man is investigated for spastic leg weakness which has come on over the previous 5 days.
He undergoes a whole spine MRI which shows:
Hyperintense T2 signal extending across the spinal cord, between the levels of T9 and T12.
Which of the following is most likely to cause this clinical and radiological presentation?
Conus medullaris syndrome
Human immunodeficiency virus
Cauda equina syndrome
Diabetes mellitus
Brown-Sequard syndrome
The radiographical features are descriptive of transverse myelitis -inflammation across most of the spinal cord.
One notable cause is viral infections (including HIV).
Conus medullaris and cauda equina syndrome are lesions of the lumbar region of the spinal cord.
Diabetes is not well documented to cause transverse myelitis.
Brown-Sequard syndrome is caused by a lesion of one half of the spinal cord only.
Causes of transverse myelitis
viral infections: varicella-zoster, herpes simplex, cytomegalovirus, Epstein-Barr, influenza, echovirus, human immunodeficiency virus
bacterial infections: syphilis, Lyme disease
post-infectious (immune mediated)
first symptom of multiple sclerosis (MS) or neuromyelitis optica (NMO)
Next question
A 34-year-old female presents due to a number of ‘funny-dos’. She describes a sensation that her surroundings are unreal, ‘like a dream’. Following this she has been told that she starts to smack her lips, although she has no recollection of doing this. What is the most likely diagnosis?
Myoclonic seizure
Focal aware seizure
Focal impaired awareness seizure
Focal to bilateral seizure
Absence seizure
Focal impaired awareness seizure
