Hemiballismus is a movement disorder which manifests as unilateral involuntary flinging movements of the proximal upper limbs. The lesion is located in the ipsilateral subthalamic nucleus.

Alpha1-antitrypsin (AAT) deficiency, first described in 1963, is one of the most common inherited disorders amongst white Caucasians. Its primary manifestation is early-onset of pan acinar emphysema. In adults, alpha1-antitrypsin deficiency leads to chronic liver disease in the fifth decade. As a cause of emphysema, it is seen in non-smokers in the fifth decade of life and during the fourth decade of life in smokers.

Symptoms of alpha1-antitrypsin (AAT) deficiency emphysema are limited to the respiratory system. Dyspnoea is the symptom that eventually dominates alpha1-antitrypsin deficiency. Similar to other forms of emphysema, the dyspnoea of alpha1-antitrypsin deficiency is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities.
The serum levels of some of the common genotypes are:
•PiMM: 100% (normal)
•PiMS: 80% of normal serum level of A1AT
•PiSS: 60% of normal serum level of A1AT
•PiMZ: 60% of normal serum level of A1AT, mild deficiency
•PiSZ: 40% of normal serum level of A1AT, moderate deficiency
•PiZZ: 10–15% (severe alpha 1-antitrypsin deficiency)

Because the patient has chronic kidney disease, we need to consider the associated adverse effects of trying to maintain normal haemoglobin levels (14-18g/dl in this patient) and instead only instigate therapy when the level falls below 11 g/dl. Thus, in this case we should just monitor the haemoglobin levels and not initiate therapy just yet.

Inclusion body myositis (IBM) is a progressive muscle disorder characterized by muscle inflammation, weakness, and atrophy (wasting). It is a type of inflammatory myopathy. IBM develops in adulthood, usually after age 50. The symptoms and rate of progression vary from person to person. The most common symptoms include progressive weakness of the legs, arms, fingers, and wrists. Some people also have weakness of the facial muscles (especially muscles controlling eye closure), or difficulty swallowing (dysphagia). Muscle cramping and pain are uncommon, but have been reported in some people. The underlying cause of IBM is poorly understood and likely involves the interaction of genetic, immune-related, and environmental factors. Some people may have a genetic predisposition to developing IBM, but the condition itself typically is not inherited. Elevated creatine kinase (CK) levels in the blood (at most ,10 times normal) are typical in IBM. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, inclusions or plaques of abnormal proteins.

Prevention of osteoporosis associated with chronic glucocorticoid therapy is done by administrating bisphosphonates. Oral bisphosphonates are indicated for patients aged above 65 who have been on steroid therapy for over 3 months, so as to reduce the risk of steroid induced osteoporosis. HRT is usually done in post menopausal women who have oestrogen related bone resorption.

Myotonic dystrophy is the most likely diagnosis here.
It is a multisystem disorder causing cognitive impairment, cataracts, cardiac problems and testicular atrophy, as well as affecting the muscles. Patients have muscle weakness, normally worse distally, and/or myotonia (which is worse in cold weather).
On examination, patients may also have frontal balding, a myopathic facies, bilateral ptosis, an ophthalmoplegia and wasting of facial muscles and other limb muscles. Myotonic dystrophy is associated with diabetes mellitus and pituitary dysfunction.
Diagnosis is normally based on clinical features with a characteristic electromyogram (EMG) of myotonic discharges. Creatine kinase is generally normal and muscle biopsy is non-specific.

Memantine is an antagonist of the NMDA (N-Methyl-D-Aspartate)-receptor subtype of glutamate receptor. It is used to slow the neurotoxicity thought to be involved in Alzheimer’s disease and other neurodegenerative diseases.

Drug interactions:
When given concomitantly with other NMDA-receptor antagonists (e.g., ketamine, amantadine) increase the risk of psychosis.
Dopamine agonists, L-dopa, and anticholinergics enhance effects of memantine.
Antispasmodics (e.g., baclofen)  enhance effects, as memantine has some antispasmodic effects.
Drugs excreted by cationic transporters in the kidney (e.g. quinine, cimetidine, ranitidine) reduce excretion.

Common adverse effects include dizziness, headache, confusion, diarrhoea, and constipation.

Treatment with ARB or ACE-I may slow further deterioration in renal function in this patient, as studies have shown that blocking of the RAS in type 2 diabetic patients improve renal function.

Acute angle closure glaucoma can manifests itself with severe headache, nausea or vomiting, very blurry or hazy vision, seeing rainbows or halos around lights and redness in the white part of the affected eye. It is caused by a rapid or sudden increase in pressure inside the eye – intraocular pressure (IOP). In order to establish the diagnosis and start treatment immediately, IOP should first be measured.

Among the give options, reactivation of tuberculosis may occur in a patient under treatment with etanercept.
Etanercept is a biological TNF inhibit commonly used to control ankylosing spondylitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, and rheumatoid arthritis.
Etanercept is a soluble receptor that binds both TNF-alpha and TNF-beta to inhibit the inflammatory response in joints and skin that is characteristic of these autoimmune disorders.
The most common adverse effects include infections (viral, bacterial, and fungal – mostly upper respiratory tract infections) and injection site reaction (erythema, itching, pain, swelling, bleeding, bruising).
Rarely it can also cause, reactivation of hepatitis B and TB, pneumocystis pneumonia, congestive cardiac failure, Steven-Johnson syndrome, toxic epidermal necrolysis, etc.

The vas deferens is a long tube that connects the epididymis to the ejaculatory ducts. It acts as a canal through which mature sperm may pass through the penis during ejaculation.

Most men with CF (97-98 percent) are infertile because of a blockage or absence of the vas deferens, known as congenital bilateral absence of the vas deferens (CBAVD). The sperm never makes it into the semen, making it impossible for them to reach and fertilize an egg through intercourse. The absence of sperm in the semen can also contribute to men with CF having thinner ejaculate and lower semen volume.

Post-concussion syndrome is a complex disorder in which various symptoms, such as headaches and dizziness, last for weeks and sometimes months after the injury that caused the concussion.

Concussion is a mild traumatic brain injury that usually happens after a blow to the head. It can also occur with violent shaking and movement of the head or body. You don’t have to lose consciousness to get a concussion or post-concussion syndrome. In fact, the risk of post-concussion syndrome doesn’t appear to be associated with the severity of the initial injury.

Post-concussion symptoms include:
Headaches
Dizziness
Fatigue
Irritability
Anxiety
Insomnia
Loss of concentration and memory
Ringing in the ears
Blurry vision
Noise and light sensitivity
Rarely, decreases in taste and smell

Loss of vision after consumption of antifreeze is a characteristic presentation of methanol poisoning.

Pathophysiology of methanol toxicity:
When ingested, methanol is absorbed rapidly via the gastrointestinal tract in less than 10 minutes. Methanol is not protein-bound and is absorbed directly into the total body water compartment.
Metabolism occurs mainly in the liver through serial oxidation via alcohol dehydrogenase and aldehyde dehydrogenase but begins with alcohol dehydrogenase present in the gastric mucosa.
Alcohol dehydrogenase oxidizes methanol to formaldehyde, and aldehyde dehydrogenase subsequently oxidizes formaldehyde to formic acid.
Formic acid is the primary toxic metabolite that accounts for the associated anion gap metabolic acidosis and end-organ damage.

Clinical presentation:
Patients who present within the first 12 to 24 hours following ingestion may appear normal, and this is described as the latent period.
Nausea, vomiting, and abdominal pain subsequently ensue, followed by CNS depression and hyperventilation due to metabolic acidosis.
Ocular symptoms associated with retinal toxicity are often evident in the form of blurry vision, decreased visual acuity, photophobia, and “halo vision.”

Treatment:
Treatment options for methanol toxicity include supportive care, fomepizole (Antizole, 4-Methylpyrazole or 4MP), ethanol, dialysis, and folate.

Among the given anti-epileptics the best drug that can be given in this patient is lamotrigine.
Topiramate, carbamazepine, phenytoin, and phenobarbital are all hepatic enzyme inducers and are associated with decreased effectiveness of the oral contraceptive (OCP) due to acceleration of the metabolism of oestrogens and progestogens.
If she is planning on pregnancy then registry studies suggest that lamotrigine would also be the best choice.
Other hepatic enzyme inducers include rifampicin, spironolactone, griseofulvin, etc.

Botulinum toxin is a neurotoxic protein from Clostridium botulinum that causes flaccid paralysis as it acts by preventing the release of Ach at the neuromuscular joint. It is the first-line treatment for cervical dystonia (torticollis) because the condition is a neurological disorder characterised by unusual muscle contractions of the neck. With the use of Botulinum toxin, the contractions would be released.

Finasteride is often prescribed for patients with Benign Prostatic Hyperplasia (BPH) or enlarged prostate. However, it has been known to cause a decrease in Prostatic Specific Antigen (PSA) levels in patients with BPH, which may lead to false negatives in a case like this, where a palpable mass has been detected and malignancy is suspected.

Fundoscopy findings of cotton wool spots and retinal tears, accompanied by a history of blurred vision, are characteristic of retinitis. Cytomegalovirus is known to cause retinitis.

In adult practice, biochemical analysis of pleural fluid plays an important part in the management of pleural effusions. Protein levels or Light’s criteria differentiate exudates from transudates, while infection is indicated by pleural acidosis associated with raised LDH and low glucose levels. In terms of treatment, the pH may even guide the need for tube drainage, suggested by pH <7.2 in an infected effusion, although the absolute protein values are of no value in determining the likelihood of spontaneous resolution or chest drain requirements. pH is therefore the most important factor.

The patient’s history points to absence seizures. Carbamazepine has been shown to aggravate generalized seizure types, especially absence seizures, because it acts directly on the ventrobasal complex of the thalamus which is critical to the neurophysiology of absence seizures.

Clozapine can cause neutropenia or agranulocytosis.

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and in patients who are intolerant to, or unresponsive to other antipsychotics.

It is a weak D2-receptor and D1-receptor blocking activity, with noradrenolytic, anticholinergic, and antihistaminic properties.

Many antipsychotic drugs can occasionally cause bone marrow depression, but agranulocytosis is particularly associated with clozapine.

Other side effects include:
Hypotension, tachycardia
Fever, sedation, seizures (with high doses)
Appetite increase
Constipation
Heartburn
Weight gain
Extrapyramidal symptoms
Agranulocytosis
Neuroleptic malignant syndrome

It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines. Prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients. NICE advises either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives.

Acute alcohol intoxication presents with pupillary dilation, thus, this is ruled out in this patient. All the other listed causes present with small pupils bilaterally.

NICE now recommends the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease. Memantine is reserved for patients with moderate to severe Alzheimer’s.

Temazepam is an orally available benzodiazepine used in the therapy of insomnia.
The soporific activity of the benzodiazepines is mediated by their ability to enhance gamma-aminobutyric acid (GABA) mediated inhibition of synaptic transmission through binding to the GABA-A receptor.
The recommended initial dose for insomnia is 7.5 mg before bedtime, increasing as needed to a maximum dose of 30 mg.

The most common side effects of temazepam are dose-related and include daytime drowsiness, lethargy, ataxia, dysarthria, and dizziness.
Tolerance develops to these side effects, but tolerance may also develop to the effects on insomnia.

Deep vein thrombosis (DVT) is a serious condition in which a blood clot forms in a deep vein, usually in the leg.

Subcutaneous low molecular weight heparin (LMWH) is the preferred treatment for most patients with acute DVT, including in pregnancy. A large meta-analyses comparing LMWH to unfractionated heparin (UFH) showed that LMWH decreased the risk of mortality, recurrent veno-thrombo embolism (VTE), and haemorrhage compared with heparin. Other advantages of LMWH may include more predictable therapeutic response, ease of administration and monitoring, and less heparin-induced thrombocytopenia. Disadvantages of LMWH include cost and longer half-life compared with heparin.

Warfarin, which is administered orally, is used if long-term anticoagulation is needed. The international normalized ratio (INR) is followed, with a target range of 2-3. Warfarin crosses the placenta and is teratogenic, causing a constellation of anomalies known as warfarin embryopathy, with greatest risk between the sixth and twelfth week of gestation.
Other options are not indicated for use.

The most appropriate intervention in this patient is intravenous hydroxocobalamin.
The clinical scenario provided is suggestive of acute cyanide toxicity secondary to burning plastics in the house fire.
Cyanide ions inhibit mitochondrial cytochrome oxidase, preventing aerobic respiration. This manifests in normal oxygen saturations, a high pO2 and flushing (or ‘brick red’ skin) brought on by the excess oxygenation of venous blood. In the question above it is important to note that the blood gas sample given is venous rather than arterial. His blood gas also demonstrates an increased anion gap, consistent with his high lactate (generated by anaerobic respiration due to the inability to use available oxygen).

The recommended treatment for moderate cyanide toxicity in the UK is one of three options: sodium thiosulfate, hydroxocobalamin or dicobalt edetate.

Among the options given is hydroxocobalamin and this is, therefore, the correct answer. Hydroxocobalamin additionally has the best side-effect profile and speed of onset compared with other treatments for cyanide poisoning.

Other options:
– Intubation would be appropriate treatment in the context of airway burns but this patient has no evidence of these, although close monitoring would be advised.
– High-flow oxygen is the treatment for carbon monoxide poisoning – a sensible differential, but this man’s very high lactate and high venous pO2 fit better with cyanide toxicity. Intravenous dexamethasone would be another treatment for airway oedema once an endotracheal tube had been placed.
– Intravenous sodium nitroprusside is a treatment for high blood pressure that can cause cyanide poisoning, and would, therefore, be inappropriate.

Note:

Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidizing enzymes
Clinical presentation:
Classical features: brick-red skin, the smell of bitter almonds
Acute: hypoxia, hypotension, headache, confusion
Chronic: ataxia, peripheral neuropathy, dermatitis

Management:
Supportive measures: 100% oxygen
Definitive: hydroxocobalamin (intravenously), also a combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously).

Sleep paralysis is a temporary inability to move or speak that occurs when you’re waking up or falling asleep. Paralysis is often accompanied by hallucinations

REM is a stage of sleep when the brain is very active and dreams often occur. The body is unable to move, apart from the eyes and muscles used in breathing, possibly to stop the person from acting out the dreams and hurting himself.

It’s not clear why REM sleep can sometimes occur while one is awake, but it has been associated with:
-not getting enough sleep (sleep deprivation or insomnia)
-irregular sleeping patterns – for example, because of shift work or jet lag
-narcolepsy – a long-term condition that causes a person to suddenly fall asleep at inappropriate times
-a family history of sleep paralysis
-sleeping on one’s back

In mild-to-moderate heroin overdoses, arterial blood gas (ABG) analysis reveals respiratory acidosis. In more severe overdoses, tissue hypoxia is common, leading to mixed respiratory and metabolic acidosis.

The normal range for PaCO2 is 35-45 mmHg (4.67 to 5.99 kPa). Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range (i.e., >45 mm Hg) with an accompanying academia (i.e., pH < 7.35). In chronic respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range, with a normal or near-normal pH secondary to renal compensation and an elevated serum bicarbonate levels (i.e., >30 mEq/L).

Arterial blood gases with pH = 7.31; pCO2 = 7.4 kPa; pO2 = 8.1 kPa would indicate respiratory acidosis.

Small cell lung cancer (SCLC) is characterized by rapid growth and early dissemination. Prompt initiation of treatment is important.

Patients with clinical stage Ia (T1N0) after standard staging evaluation may be considered for surgical resection, but combined treatment with chemotherapy and radiation therapy is the standard of care. Radiation therapy is often added at the second cycle of chemotherapy.

Historically, patients undergoing surgery for small cell lung cancer (SCLC) had a dismal prognosis. However, more recent data suggest that patients with true stage I SCLC may benefit from surgical resection.

Common sites of hematogenous metastases include the brain, bones, liver, adrenal glands, and bone marrow. The symptoms depend upon the site of spread.

In any patient with asthma, a decreasing PaO2 and an increasing PaCO2, even into the normal range, indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.

Chest tightness and cough, which are the most common symptoms of asthma, are probably the result of inflammation, mucus plugs, oedema, or smooth muscle constriction in the small peripheral airways. Because major obstruction of the peripheral airways can occur without recognizable increases of airway resistance or FEV1, the physiologic alterations in acute exacerbations are generally subtle in the early stages. Poorly ventilated alveoli subtending obstructed bronchioles continue to be perfused, and as a consequence, the P(A-a)O2 increases and the PaO2 decreases. At this stage, ventilation is generally increased, with excessive elimination of carbon dioxide and respiratory alkalemia.