Lewy body dementia is an increasingly recognised cause of dementia, accounting for up to 20% of cases. The characteristic pathological feature is alpha-synuclein cytoplasmic inclusions (Lewy bodies) in the substantia nigra, paralimbic and neocortical areas. Neuroleptics should be avoided in Lewy body dementia as patients are extremely sensitive and may develop irreversible parkinsonism. Questions may give a history of a patient who has deteriorated following the introduction of an antipsychotic agent.

Steps required in performing the Wilcoxon signed rank test:

1 State the null hypothesis and, in particular, the hypothesized value for comparison
2 Rank all observations in increasing order of magnitude, ignoring their sign. Ignore any observations that are equal to the hypothesized value. If two observations have the same magnitude, regardless of sign, then they are given an average ranking
3 Allocate a sign (+ or -) to each observation according to whether it is greater or less than the hypothesized value (as in the sign test)
4 Calculate:
R+ = sum of all positive ranks
R- = sum of all negative ranks
R = smaller of R+ and R-
5 Calculate an appropriate P value What makes this test the most appropriate for this study is that the data is non-parametric, paired and comes from the same population.

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

The human cell has two type of DNA: Nuclear DNA and Mitochondrial DNA (MtDNA). A MtDNA copy is passed down entirely unchanged, through the maternal line. Males cannot pass their MtDNA to their offspring although they inherit a copy of it from their mother. Mitochondrial inheritance therefore has the following characteristics:
– Inheritance is only via the maternal line
– All children of affected males will not inherit the disease
– All children of affected females will inherit it

In a patient with chronic alcoholism, one can expect confabulations, which point towards a diagnosis of Korsakoff’s syndrome.

Korsakoff’s is characterized by confabulation and amnesia, typically occurring in alcoholics secondary to chronic vitamin B1 (thiamine) deficiency.

Other options:
Dysthymia refers to mild depression.
Hydrophobia is a feature of rabies
Lilliputians may be observed in delirium tremens.
Perseveration is repetitive speech patterns, commonly seen after traumatic brain injury.

According to the Caine criteria, the presence of any two among the four following criteria can be used to clinically diagnose Wernicke’s Encephalopathy:
Dietary deficiency
Oculomotor abnormalities
Cerebellar dysfunction
Either altered mental status or mild memory impairment
Korsakoff psychosis:
Altered mental status – disorientation, confabulations
Oculomotor findings – most often horizontal nystagmus, ophthalmoplegia, cranial nerve IV palsy, conjugate gaze
Ataxia – wide-based gait

Treatment:
The mainstay of treatment in an acute presentation is thiamine replacement.
Electrolyte abnormalities should be corrected and fluids replaced.
In particular, magnesium requires replacement, as thiamine-dependent enzymes cannot operate in a magnesium-deficient state.
After the acute phase of vitamin and electrolyte replacement, memory rehabilitation is beneficial in Korsakoff syndrome.

There is a strong suspicion of drug-induced acute tubulo-interstitial nephritis with the classic triad of symptoms of rash, joint pain and eosinophils in the blood, associated with non-specific symptoms of fever and fatigue. This can be confirmed with renal biopsy showing interstitial oedema with a heavy infiltrate of inflammatory cells and variable tubular necrosis.

Confusion and pink mucosae are typical features of CO poisoning.
The patient often presents, most commonly with headaches, and other symptoms like malaise, nausea, and dizziness.

Carbon monoxide (CO) poisoning, considered as the great imitator of other diseases as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.

Features of carbon monoxide toxicity
– Headache: 90% of cases
– Nausea and vomiting: 50%
– Vertigo: 50%
– Confusion: 30%
– Subjective weakness: 20%
– Severe toxicity: ‘pink’ skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death

Treatment:
Use of Hyperbaric oxygen therapy (HBOT) for treating mild to moderate CO poisoning is not routine.
The selection criteria for HBOT in cases of CO poisoning include:
• COHb levels > 20-25%
• COHb levels > 20% in pregnant patient
• Loss of consciousness
• Severe metabolic acidosis (pH <7.1)
• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)

The most likely organism is enterohemorrhagic verotoxin-producing E.coli. It usually causes haemolytic uremic syndrome.
Crohn’s disease rarely manifests in an acute manner.
Polio and giardiasis usually manifest with non-bloody diarrhoea.

Avascular necrosis (AVN) of the femoral head is a pathological process that results from disruption of the blood supply to the bone and occurs most commonly in the femoral epiphysis. Patients usually present with pain and limited joint motion. The mechanism involves impaired circulation to a specific area that ultimately becomes necrotic. AVN is most frequently associated with high doses of oral and intravenous corticosteroids and prolonged duration of therapy. Cancer patients receiving chemotherapy are usually also treated with corticosteroids.

The most possible diagnosis is a pituitary tumour. Pituitary tumours compress the optic chiasm inferiorly and can cause visual field defects (bitemporal hemianopia or quadrantanopia). Temporal arteritis usually develops in older people and acute glaucoma usually requires a family history. Amaurosis fugax is classed as a stroke and usually leads to reversible unilateral vision loss. A subconjunctival haemorrhage does not typically produce the symptoms described.

Early morning waking is a highly suggestive feature of depression in this patient.

NICE use the DSM-IV criteria to grade depression:
1. Depressed mood most of the day, nearly every day
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day
3. Significant weight loss or weight gain when not dieting or decrease or increase in appetite nearly every day
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation nearly every day
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt nearly every day
8. Diminished ability to think or concentrate, or indecisiveness nearly every day
9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

Subthreshold depressive symptoms: Fewer than 5 symptoms
Mild depression: Few, if any, symptoms over the 5 required to make the diagnosis, and symptoms result in only minor functional impairment
Moderate depression: Symptoms or functional impairment are between ‘mild’ and ‘severe’
Severe depression: Most symptoms and the symptoms markedly interfere with functioning. Can occur with or without psychotic symptoms.

Treatment of depression:
Psychotherapy (in the form of cognitive behavioural therapy or interpersonal therapy) alone or in combination with medications such as:
– Selective serotonin reuptake inhibitors (SSRIs)
– Serotonin/norepinephrine reuptake inhibitors (SNRIs)
– Atypical antidepressants
– Serotonin-Dopamine Activity Modulators (SDAMs)
– Tricyclic antidepressants (TCAs)

There is also empirical support for the ability of CBT to prevent relapse.

Electroconvulsive therapy is a useful treatment option for patients with severe depression refractory to medication or those with psychotic symptoms. The only absolute contraindications is raised intracranial pressure.

Side-effects:
Headache
Nausea
Short term memory impairment
Memory loss of events before ECT
Cardiac arrhythmia
Long-term side-effects: Impaired memory

The patient is asymptomatic but matches the diagnostic criteria for multiple myeloma (MM). Therefore, the underlying diagnosis of this condition is smouldering multiple myeloma (SMM). SMM is an early precursor to MM. Its treatment is typically to watch and wait.

MM is a neoplasm of the bone marrow plasma cells. Peak incidence is in patients aged 60–70 years.

Clinical features of MM include:
1. Ostealgia, osteoporosis, pathological fractures (typically vertebral), and osteolytic lesions
2. Lethargy
3. Infections
4. Hypercalcaemia
5. Renal failure
6. Other features: amyloidosis e.g. macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

Diagnosis of MM is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon. GLP-1 is released in response to meal intake.
The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the ileal brake mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake.
Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycaemia.

Women with Sjögren syndrome are likely to experience more complications during pregnancy than women without an autoimmune disease as the anti-Ro and anti-La antibodies cross the placenta and lead to various life threatening complications. Studies show a high incidence of poor fetal outcomes for these patients. Congenital heart block, neonatal lupus, congestive cardiac failure, hydrops fetalis can all be caused as a result of Sjogren syndrome.

In Wilson’s disease, serum caeruloplasmin is decreased. Skin pigmentation is not increased, but may become jaundiced. 24 hour urine copper excretion is increased. Hepatic copper concentration is increased. Serum copper level is also increased. Key point: high copper. Remember Kayser-Fleisher rings for the eyes in Wilson’s disease.

Pre-eclampsia is excluded from negative proteinuria. White coat hypertension is excluded with ambulatory blood pressure monitoring. Pregnancy induced hypertension develops after 20 weeks of gestation. So the most likely answer is pre-existing hypertension. She should be investigated for a secondary cause for hypertension.

This is a typical picture of acute chest syndrome (ACS). According to the British Committee for Standards in Haematology (BCSH), ACS is defined as ‘an acute illness characterised by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on chest X-ray’. ACS occurs in sequestration crisis, which is one of the four main types of crises occurring in sickle cell disease.

The fundamentals of initial management are as follows:
1. Oxygen therapy to maintain saturation >95%
2. Intravenous fluids to ensure euvolemia
3. Adequate pain relief
4. Incentive spirometry in all patients presenting with rib or chest pain
5. Antibiotics with cover for atypical organisms
6. Bronchodilators if asthma co-exists with acute chest syndrome, or if there is an evidence of acute bronchospasm on auscultation
7. Early consultation with the critical care team and haematology department

A senior haematologist then makes a decision as to whether a simple or exchange transfusion is necessary in order to achieve a target Hb of 10.0–11.0g/dL in either instance.

Sickle Cell Crises:
Sickle cell anaemia is characterised by periods of good health with intervening crises:
1. Sequestration crisis: acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates)

2. Thrombotic (painful or vaso-occlusive) crisis: precipitated by infection, dehydration, and deoxygenation

3. Aplastic crisis: sudden fall in haemoglobin without marked reticulocytosis, usually occurring secondary to parvovirus infection

4. Haemolytic crisis: fall in haemoglobin secondary to haemolysis, rare type of sickle cell crises

The major endocrine functions of adrenal gland are to produce catecholamines and steroids. Catecholamine, synthesized by the adrenal medulla, is responsible for blood pressure and blood flow regulation whereas steroids produced by the cortex control energy and water homeostasis and immune responses. Glucocorticoids, a major group of adrenal steroids, have a stimulatory effect on catecholamine synthesis in the medulla.

The combination of frequent infections, eczema, and thrombocytopaenia are characteristic of Wiskott-Aldrich syndrome, which is due to an abnormality in the WASP gene. It is an X-linked recessive disorder that causes primary immunodeficiency owing to a combined B- and T-cell dysfunction.

The other listed options are:
1. PKD1: polycystic kidney disease
2. CFTR: cystic fibrosis
3. HFE1: haemochromatosis
4. RET: multiple endocrine neoplasia, Hirschsprung’s disease

Transposition of the great arteries results in a significant hypoxemic status that is observed clinically by central cyanosis. The bluish discoloration of the skin and mucous membranes is therefore the basic pattern of clinical presentation in transposition. Its onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulations. Limited intercirculatory mixing, usually present if the ventricular septum is intact or the atrial septal defect is restrictive, is related to progressive and profound central cyanosis evident within the first hours of life. Tachypnoea, tachycardia, diaphoresis, poor weight gain, a gallop rhythm, and eventually hepatomegaly can be then detected later on during infancy. Heart murmurs associated with left outflow tract obstruction, due to a persistent arterial duct or a septal defect may be heard, but they are not a constant finding.

Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. It is secreted mainly by macrophages and monocytes and acts as a costimulator of T cell and B cell proliferation.

This patient’s symptoms of anaemia, leukopenia, and elevated non-albumin protein concentration with fatigue and weight loss, point to myeloma. Thus plasma protein electrophoresis or Serum Protein Electrophoresis (SPE) is indicated when there is suspicion of myeloma.

The patient (known case of acromegaly) seems to have developed cholelithiasis (presenting with right upper quadrant pain) probably due to octreotide.

It is a long-acting analogue of somatostatin which is released from D cells of the pancreas and inhibits the release of growth hormone, glucagon, and insulin.

Uses
– Acute treatment of variceal haemorrhage
– Acromegaly
– Carcinoid syndrome
– Prevent complications following pancreatic surgery
– VIPomas
– Refractory diarrhoea

Adverse effects
Gallstones (secondary to biliary stasis)

Other options:
– Bromocriptine – a dopamine agonist with side effects arising from its stimulation of the brain vomiting centre.
– Desmopressin – predominantly used in patients with diabetes insipidus by increasing the presence of aquaporin channels in the distal collecting duct to increase water reabsorption from the kidneys. The main side effects include headache and facial flushing due to hypertension.
– Metformin – mainly reduces hepatic gluconeogenesis in patients with type 2 diabetes, common side effects include diarrhoea, vomiting, and lactic acidosis
– Levothyroxine – synthetic thyroxine used in patients with hypothyroidism, common side effects result from incorrect dosing and mimic the symptoms of hyperthyroidism.

It has been determined that HPV infection is the most powerful epidemic factor. This virus is needed, but not sufficient for the development of cervical cancer.
The WHO’s International Agency for Research on Cancer (IARC) classified HPV infection as carcinogenic to humans (HPV types 16 and 18), probably carcinogenic (HPV types 31 and 33) and possibly carcinogenic (other HPV types except 6 and 11).
Tobacco smoking, the use of contraceptives, and the number of births are factors that showed no statistically significant deviations in the studied population compared to other countries in the region, as well as European countries. They have an equal statistical significance in all age groups.

This case presents with sensorimotor neuropathy secondary to his DM. The progression of the neuropathy, known dying-back neuropathy, is a distal axonopathy or axonal degeneration as where the sensorimotor loss begins distally and travels proximally.

The cause of Vitiligo is typically unknown. It is believed to be due to genetic susceptibility that is triggered by an environmental factor such that an autoimmune disease occurs. This results in the destruction of skin pigment cells. Risk factors include a family history of the condition or other autoimmune diseases, such as hyperthyroidism, alopecia areata, and pernicious anaemia. Vitiligo is classified into two main types: segmental and non-segmental. Most cases are non-segmental meaning they affect both sides and typically get worse with time. The prevalence of vitiligo is 0.5-1% of populations worldwide. Typical sites include backs of hands, wrists, knees, neck and around body orifices. The Koebner phenomenon refers to skin lesions appearing on lines of trauma. This occurs in vitiligo secondary to scratching.

Behçet disease is a rare vasculitic disorder that is characterized by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. The systemic manifestations can be variable. Ocular disease has the greatest morbidity, followed by vascular disease generally from active vasculitis. Cutaneous manifestations can occur in up 75% of patients with Behcet disease and can range from acneiform lesions, to nodules and erythema nodosum. GI manifestations can be severe. Differentiating Behçet disease from active inflammatory bowel disease can be clinically difficult. Herpes would have ideally responded to acyclovir. Sarcoidosis does not have genital and oral ulcerations.

J waves in an ECG is associated with hypothermia, hypercalcemia, the Brugada syndrome, and idiopathic ventricular fibrillation. The other responses are all associated with atrial myxoma

The question describes an alcohol abusing man with chronic epigastric discomfort, radiating into his back, worse with meals, and foul-smelling stools, weight loss, as well as chronic nausea. This is likely, thus chronic pancreatitis due to alcohol abuse. Hepatomegaly and peripheral neuropathy secondary to anaemia support the diagnosis of long term alcohol abuse. Bacterial overgrowth may present with diarrhoea and is a less likely diagnosis than pancreatitis. Celiac disease is a less likely diagnosis than pancreatitis, and you would also expect mention of diarrhoea. VIPoma would also likely present with diarrhoea. Cecal carcinoma would more than likely present with blood in the stool.

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumours: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumours, adrenocortical carcinoma (ACC), and leukaemia. LFS is diagnosed in individuals meeting established clinical criteria or in those who have a germline pathogenic variant in TP53 regardless of family cancer history.