Cerebral venous sinus thrombosis (CVST) is associated with headache (>90% of cases), seizures, focal weakness (40%) and papilledema (40%), all seen in this patient.
Risk factors for CVST include genetic or acquired prothrombotic disorders, pregnancy, the oral contraceptive pill, vasculitis, malignancy, dehydration and infection. However, there are multiple other associated factors.
Diagnosis is normally confirmed with magnetic resonance venography (MRV). Treatment is with anticoagulation, initially with heparin and subsequently with warfarin.

The following are conditions commonly associated with pyoderma gangrenosum:
Inflammatory bowel disease:
– Ulcerative colitis
– Crohn’s disease
Arthritides:
– Rheumatoid arthritis
– Seronegative arthritis
Haematological disease:
– Myelocytic leukaemia[8]
– Hairy cell leukaemia
– Myelofibrosis
– Myeloid metaplasia
– Monoclonal gammopathy
Autoinflammatory disease:
– Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome)
– Granulomatosis with polyangiitis

Bombesin is a tumour marker elevated in small cell lung carcinomas, as well as in gastric carcinomas and retinoblastomas.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

This patient is a case of chronic myeloid leukaemia (CML) and should be started on imatinib as the first-line drug of choice.

Soluble guanylyl cyclase (GC-1) is the primary receptor of nitric oxide (NO) in smooth muscle cells and maintains vascular function by inducing vasorelaxation in nearby blood vessels. GC-1 converts guanosine 5′-triphosphate (GTP) into cyclic guanosine 3′,5′-monophosphate (cGMP), which acts as a second messenger to improve blood flow.

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. In some patients however, there is a combination of clinical patterns. In progressive bulbar palsy there is palsy of the tongue and muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei. This carries the worst prognosis.

Liver flap is pathognomonic for liver failure. Paracetamol (also known as acetaminophen) overdose usually presents with symptoms including liver failure, resulting in confusion, jaundice, and coagulopathy a few days after overdose. The first 24 hours, people usually have minimal symptoms. Diagnosis is based on blood levels of acetaminophen at specific times after it was taken (see reference). If she took it a few days ago, levels may indeed be undetectable. The hepatitis B serology suggests prior vaccination. Wilson’s disease is not the most likely diagnosis given her presentation. The AST:ALT ratio would be expected to be reversed in alcohol induced liver failure.

The key to this question is anti-smooth muscle antibodies. This is a finding of autoimmune hepatitis, which can be seen in type I diabetics. This also fits with her clinical picture. If you know these two facts, you should get every question correct regarding autoimmune hepatitis. Liver function testing is the best answer, then and should be elevated to indicate inflammation of the liver. Hepatic US, CK, thyroid function testing, short synacthen test are not helpful in the diagnosis of autoimmune hepatitis.

The upper motor neurone signs in this patient point towards a diagnosis of spinal cord compression above the level of L1 and rules out cauda equina syndrome.

Spinal cord compression is an oncological emergency and affects up to 5% of cancer patients. Extradural compression accounts for the majority of cases, usually due to vertebral body metastases. One of the most common causes of spinal cord compression is osteoarthritis. It is also more commonly seen in patients with lung, breast, or prostate cancer.

Clinical features include:
1. Back pain: the earliest and most common symptom, may worsen on lying down or coughing
2. Lower limb weakness
3. Sensory changes: sensory loss and numbness
4. Neurological signs: depending on the level of the lesion.
Lesions above L1 usually result in upper motor neurone signs in the legs. Lesions below L1 usually cause lower motor neurone signs in the legs and perianal numbness. Tendon reflexes are increased below the level of the lesion and absent at the level of the lesion.

Management options are:
1. High-dose oral dexamethasone
2. Urgent MRI for consideration of radiotherapy or surgery

Lactic acidosis is occasionally responsible for metabolic acidosis in diabetics. It may occur in the presence of normal blood levels of the ketone bodies, and such cases are often described as having “non-ketotic diabetic acidosis.
It is most commonly associated with tissue hypoperfusion and states of acute circulatory failure.
Appropriate measures include treatment of shock, restoration of circulating fluid volume, improved cardiac function, identification of sepsis source, early antimicrobial intervention, and resection of any potential ischemic regions. Reassessment of lactate levels for clearance assists ongoing medical management.

Entrapment of the median nerve by pronator teres causes a median nerve neuropathy, which is worse during pronation of the forearm. Examination should involve excluding carpal tunnel syndrome and pronation of the affected forearm against resistance, which brings on the pain. Unlike carpal tunnel syndrome, the median nerve proximal to the wrist may be tender to palpation.

Hepatorenal syndrome is renal vasoconstriction that cannot overcome the effects of splanchnic vasodilation. Vasoactive mediators cause this splanchnic vasodilation, reducing SVR, which is sensed by the juxtaglomerular apparatus, activating the RAAS system, leading to renal vasoconstriction. However, the overall splanchnic vasodilation effect is greater than this renal vasoconstriction effect.

The most appropriate treatment in this patient would be to stop warfarin therapy and keep the patient under observation.

The drugs that lead to enhanced potency of warfarin include: disulfiram, trimethoprim-sulphamethoxazole, metronidazole, phenylbutazone, aspirin, heparin, and clofibrate.
Liver disease, thrombocytopenia, hyperthyroidism also increase the oral anticoagulant potency.
If the patient has minor bleeding and the international normalized ratio (INR) is >6.0, warfarin should be stopped; the INR should be rechecked daily and in addition to the stoppage of warfarin, vitamin K 2.5 mg oral or 0.5 mg intravenously should also be administered.
In a patient with INR of 2.0 or 3.0, it takes two or three times longer for that individual’s blood to clot than someone who is not taking any anticoagulants. Most patients on warfarin have an INR goal of 2 to 3.

If there is major bleeding then prothrombin complex concentrates 50 u/kg or fresh-frozen plasma 15 ml/kg may be considered.

A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. There are six antimuscarinic drugs currently marketed for the treatment of urge incontinence: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin.

Cataract is a condition characterized by clouding of the lens of the eye. This condition most frequently occurs due to age-related degenerative processes in the lens, but can also be associated with ocular trauma, metabolic disorders, side-effects of drugs, or congenital infections. The clouding causes distortion of light, as it passes through the lens, resulting in visual impairment and glare. Initially, a cataract presents discretely and may even go unnoticed, but the visual impairment worsens as the cataract grows larger.

Diagnosis is typically established on the basis of a thorough history and direct visualization of the cataract (by means of slit-lamp microscopy). Surgery is indicated with significant visual impairment and involves lens extraction and implantation of an artificial lens. Untreated cataracts eventually lead to complete blindness.

The patient is most likely to have Addison’s disease as he has a history of autoimmune disease, hyperkalaemia and hypotension.
It is important to keep an Addisonian crisis on the differential in cases of shock, especially since adrenal crisis can be the patient’s first presentation of adrenal insufficiency.
Patients with Addison’s disease are prone to developing hypoglycaemia due to loss of the glucogenic effect of glucocorticoids. Given the sudden deterioration, a glucose level must be checked.

Carbon monoxide (CO) is a colourless, odourless gas produced by incomplete combustion of carbonaceous material. Clinical presentation in patients with CO poisoning ranges from headache and dizziness to coma and death. Hyperbaric oxygen therapy can significantly reduce the morbidity of CO poisoning, but a portion of survivors still suffer significant long-term neurologic and affective sequelae.

Complaints:
Malaise, flulike symptoms, fatigue
Dyspnoea on exertion
Chest pain, palpitations
Lethargy
Confusion
Depression
Impulsiveness
Distractibility
Hallucination, confabulation
Agitation
Nausea, vomiting, diarrhoea
Abdominal pain
Headache, drowsiness
Dizziness, weakness, confusion
Visual disturbance, syncope, seizure
Faecal and urinary incontinence
Memory and gait disturbances
Bizarre neurologic symptoms, coma

Vital signs may include the following:
Tachycardia
Hypertension or hypotension
Hyperthermia
Marked tachypnoea (rare; severe intoxication often associated with mild or no tachypnoea)
Although so-called cherry-red skin has traditionally been considered a sign of CO poisoning, it is in fact rare.

The clinical diagnosis of acute carbon monoxide (CO) poisoning should be confirmed by demonstrating an elevated level of carboxyhaemoglobin (HbCO). Either arterial or venous blood can be used for testing. Analysis of HbCO requires direct spectrophotometric measurement in specific blood gas analysers. Elevated CO levels of at least 3–4% in non-smokers and at least 10% in smokers are significant.

Polymerase chain reaction (PCR) is a method widely used in molecular biology to make several copies of a specific DNA segment. Using PCR, copies of DNA sequences are exponentially amplified to generate thousands to millions of more copies of that particular DNA segment.The main advantage of PCR is its sensitivity: only one strand of sample DNA is needed to detect a particular DNA sequence. It now has many uses including prenatal diagnosis, detection of mutated oncogenes and diagnosis of infections. PCR is also extensively used in forensics.

Pregnancies affected by T1DM are at increased risk for preterm delivery, preeclampsia, macrosomia, shoulder dystocia, intrauterine fetal demise, fetal growth restriction, cardiac and renal malformations, in addition to rare neural conditions such as sacral agenesis.
Successful management of pregnancy in a T1DM patient begins before conception. Research indicates that the implementation of preconception counselling, emphasizing strict glycaemic control before and throughout pregnancy, reduces the rate of perinatal mortality and malformations.
The 2008 bulletin from the National Institute for Health and Clinical Excellence recommends that preconception counselling be offered to all patients with diabetes. Physicians are advised to guide patients on achieving personalized glycaemic control goals, increasing the frequency of glucose monitoring, reducing their HbA1C levels, and recommend avoiding pregnancy if the said level is > 10%.
Other sources suggest deferring pregnancy until HbA1C levels are > 8%, as this margin is associated with better outcomes.

Throughout pregnancy the tubular reabsorption of glucose is less effective than in the non-pregnant state, this leads to glycosuria.

In restless leg syndrome (RLS), males and females are thought to be equally affected. RLS is a syndrome of spontaneous, continuous lower limb movements that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of the general population and a family history may be present.

The oedema is an effect of the a decreased cardiac output that increases renin release which leads to vasoconstriction and sodium and water retention.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of neuromuscular transmission in which release of acetylcholine (ACh) is impaired, causing a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation, and autonomic changes.

In 40% of patients with LEMS, cancer is present when the weakness begins or is found later. This is usually a small cell lung cancer (SCLC). However, LEMS has also been associated with non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder.

Gastrin is released from G cells in the antrum of the stomach after a meal. It stimulates parietal cells to release HCl. Gastrin is stimulated by a number of things: antrum distention, vagal stimulation, peptides (especially amino acids) in the stomach, hypercalcemia. Gastrin release is inhibited by acid, SST, GIP, VIP, secretin, glucagon, and calcitonin.

V/Q scanning carries a slightly increased risk of childhood cancer compared with CTPA – 1/280,000 versus less than 1/1,000,000 – but carries a lower risk of maternal breast cancer. The rest of the options are true.

The history is suggestive of hypertrophic obstructive cardiac myopathy. The degree of left ventricular hypertrophy is strongly associated with sudden cardiac death.

Normal distribution, also known as the Gaussian distribution, is a probability distribution that is symmetric about the mean. The normal distribution has the following properties:
– It is symmetric around the mode, the median and the mean of the distribution.
– It is unimodal
– The area under the curve and over the x-axis is unity (i.e. equal to one).
– Its density has two inflection points.
– Its density is log-concave.
The standard deviation (SD) is a measure of how much dispersion exists from the mean. SD = square root (variance)

Primary amyloidosis is characterised by abnormal protein build-up in the tissues and organ such as the heart, liver, spleen, kidneys, skin, ligaments, and nerves. However, the most common cause of death in patients with primary amyloidosis is heart failure.

Arterial ischemia ulcers present with many of the symptoms observed in this patient: ulcer on the lower extremities, pain, swelling, yellow sores, a punched-out appearance, the foot turning red when dangling from a bed. Smoking a lot is also known to be a causative factor here. This type of ulcer develops due to damage to the arteries caused by a lack of blood flow to the tissue – they are also deep wounds. Venous ischemic ulcers usually form in the knee or inner ankle area as opposed to the foot.

Heterochromia (difference in iris colour) is seen in congenital Horner’s syndrome, as well as anhidrosis. Other features of non-congenital Horner’s include miosis, ptosis and enophthalmos.