neurology Flashcards
Internuclear Ophthalmology pathophysiology
https://youtu.be/MWJz75R01s4
Pruritus
The table below lists the main characteristics of the most important causes of pruritus
Condition Notes
Liver disease History of alcohol excess
Stigmata of chronic liver disease: spider naevi, bruising, palmar erythema, gynaecomastia etc
Evidence of decompensation: ascites, jaundice, encephalopathy
Iron deficiency anaemia Pallor
Other signs: koilonychia, atrophic glossitis, post-cricoid webs, angular stomatitis
Polycythaemia Pruritus particularly after warm bath
‘Ruddy complexion’
Gout
Peptic ulcer disease
Chronic kidney disease Lethargy & pallor
Oedema & weight gain
Hypertension
Lymphoma Night sweats
Lymphadenopathy
Splenomegaly, hepatomegaly
Fatigue
Other causes:
hyper- and hypothyroidism
diabetes
pregnancy
'senile' pruritus
urticaria
skin disorders: eczema, scabies, psoriasis, pityriasis rosea
what is treatmet failure in osteoporosis
The patient’s bone mineral density has improved secondary to her treatment with alendronic acid. However, her recent back pain and abnormal thoracolumbar x-ray suggest she has suffered from a osteoporotic vertebral fracture. In one study, continuing alendronic acid from five to ten years treatment reduced the incidence of clinical vertebral fractures in all patients regardless of T score. Therefore, continuing alendronic acid treatment would be recommended for this patient.
Due to increased awareness of the potential complications of long-term bisphosphonate treatment, treatment breaks (or ‘drug holidays’) are now employed for some patients. Specifically, a treatment break should be considered for patients less than 75 years old, with femoral neck T score > - 2.5, no history of osteoporotic vertebral fracture and deemed low risk following assessment by WHO Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidance. For such a patient, treatment would typically be suspended for two years with repeat DEXA scan at the end of that period, or sooner in the event of fragility fracture.
Parenteral osteroporosis treatments such as zoledronic acid or denosumab should be considered if patient is intolerant of oral bisphosphonates or in the event of treatment failure (defined as two or more fractures on treatment, or one fracture and a fall in bone mineral density)
osteoporosis management and guidelines
NICE guidelines were updated in 2008 on the secondary prevention of osteoporotic fractures in postmenopausal women.
Key points include
treatment is indicated following osteoporotic fragility fractures in postmenopausal women who are confirmed to have osteoporosis (a T-score of - 2.5 SD or below). In women aged 75 years or older, a DEXA scan may not be required 'if the responsible clinician considers it to be clinically inappropriate or unfeasible' vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete alendronate is first-line around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate (see treatment criteria below) strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates (see treatment criteria below)
Treatment criteria for patients not taking alendronate
Unfortunately, a number of complicated treatment cut-off tables have been produced in the latest guidelines for patients who do not tolerate alendronate
These take into account a patients age, theire T-score and the number of risk factors they have from the following list:
parental history of hip fracture alcohol intake of 4 or more units per day rheumatoid arthritis
It is very unlikely that examiners would expect you to have memorised these risk tables so we’ve not included them in the revision notes but they may be found by following the NICE link. The most important thing to remember is:
the T-score criteria for risedronate or etidronate are less than the others implying that these are the second line drugs if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or raloxifene may be given based on quite strict T-scores (e.g. a 60-year-old woman would need a T-score < -3.5) the strictest criteria are for denosumab
Supplementary notes on treatment
Bisphosphonates
alendronate, risedronate and etidronate are all licensed for the prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosis all three have been shown to reduce the risk of both vertebral and non-vertebral fractures although alendronate, risedronate may be superior to etidronate in preventing hip fractures ibandronate is a once-monthly oral bisphosphonate
Vitamin D and calcium
poor evidence base to suggest reduced fracture rates in the general population at risk of osteoporotic fractures - may reduce rates in frail, housebound patients
Raloxifene - selective oestrogen receptor modulator (SERM)
has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but has not yet been shown to reduce the risk of non-vertebral fractures has been shown to increase bone density in the spine and proximal femur may worsen menopausal symptoms increased risk of thromboembolic events may decrease risk of breast cancer
Strontium ranelate
'dual action bone agent' - increases deposition of new bone by osteoblasts (promotes differentiation of pre-osteoblast to osteoblast) and reduces the resorption of bone by inhibiting osteoclasts concerns regarding the safety profile of strontium have been raised recently. It should only be prescribed by a specialist in secondary care due to these concerns the European Medicines Agency in 2014 said it should only be used by people for whom there are no other treatments for osteoporosis increased risk of cardiovascular events: any history of cardiovascular disease or significant risk of cardiovascular disease is a contraindication increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended it is not used in patients with a history of venous thromboembolism may cause serious skin reactions such as Stevens Johnson syndrome
Denosumab
human monoclonal antibody that inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts given as a single subcutaneous injection every 6 months initial trial data suggests that it is effective and well tolerated
Teriparatide
recombinant form of parathyroid hormone very effective at increasing bone mineral density but role in the management of osteoporosis yet to be clearly defined
Hormone replacement therapy
has been shown to reduce the incidence of vertebral fracture and non-vertebral fractures due to concerns about increased rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is suffering from vasomotor symptoms
Hip protectors
evidence to suggest significantly reduce hip fractures in nursing home patients compliance is a problem
Falls risk assessment
no evidence to suggest reduced fracture rates however, do reduce rate of falls and should be considered in management of high risk patients
colonoscopic surveillance
The guidance for colonoscopic surveillance is dependent on the patient’s risk profile and can be divided into low risk, intermediate risk, and high risk. A patient with 2 small adenomas <10mm in size is at a low risk of developing colorectal cancer. Therefore a repeat colonoscopy should be offered at 5 years.
Patients at intermediate risk should be offered a colonoscopy at 3 years and patients at high risk should be offered a colonoscopy at 1 year.
Link to the NICE guidance:
https://www.nice.org.uk/guidance/cg118/chapter/1-Guidance
Sensitivity of the different investigations in MG
The patient is presenting with symptoms and signs consistent with myasthenia gravis. All of the above investigations would be appropriate in this context but have variable sensitivities for myasthenia gravis as listed below:
Single fibre electromyography: sensitivity 92-100 % Repetitive nerve stimulation neurophysiology: sensitivity 70 % Serum acetylcholine receptor antibodies: sensitivity 85 % Serum muscle specific tyrosine kinase antibodies: sensitivity 40-70 %
The Edrophonium (Tensilon) test has a high sensitivity for myasthenia gravis but is no longer used due to risk of fatal cardiac arrhythmia. Around 10 % of patients with myasthenia gravis also have a thymoma and therefore CT scanning is an important part of assessment of these patients. However, this investigation will no yield a diagnosis
Indications and complications of plasma exchange
Indications for plasma exchange (also known as plasmapheresis)
Guillain-Barre syndrome myasthenia gravis Goodpasture's syndrome ANCA positive vasculitis if rapidly progressive renal failure or pulmonary haemorrhage TTP/HUS cryoglobulinaemia hyperviscosity syndrome e.g. secondary to myeloma
Complications of plasma exchange
hypocalcaemia: due to the presence of citrate used as an anticoagulant for the extracorporeal system
metabolic alkalosis
removal of systemic medications
coagulation factor depletion
immunoglobulin depletion
Foods and medications that can affect results of 5HIAA 24hr urinary sample collection for carcinoid syndrome
False positives False negatives Paracetamol Aspirin Naproxen Levodopa Caffeine Methyldopa Fluorouracil ACTH
Foods causing false positive 5-HIAA urinary collection results:
Banana
Avocado
Aubergine
Pineapple
Plums
Walnuts
Tomatoes
Differentiating between Bartters syndome and Gitelman
Both have normotesive hypokalemic metabolic alkalosis and autonomi recessive with Barthers associated with hypercalcluria and Gitelmans assocaited with hypocalciuria .
Gitelman’s syndrome is an autosomal recessive disorder resulting in a normotensive hypokalaemic metabolic alkalosis with hypocalciuria and is often accompanied with hypomagnesaemia. The defect is in the thiazide-sensitive sodium chloride symporter within the distal convoluted tubules, in contrast to Bartter’s syndrome which presents in the same way but with hypercalciuria owing to a defect within the ascending loop of Henle. Patients with both conditions are often asymptomatic or may complain of fatigue, cramps and weakness. Conn’s disease is associated with hypertension and in this instance the aldosterone level is normal with an elevated renin, making this diagnosis unlikely. Both Addison’s disease and laxative abuse are associated with a metabolic acidosis; in Addison’s serum potassium also tends to be elevated. The best answer is, therefore,
Multifocal motor neuropathy with conduction block
The answer here is the condition called multifocal motor neuropathy with conduction block (MMNCB). These patients are usually younger to middle-aged men who develop focal arm weakness in the distribution of a named nerve. It usually happens quite suddenly (e.g. over a week) and they are often mistaken as a stroke at first presentation. However, over several months additional named motor nerves become involved asymmetrically such that MMNCB may eventually look like motor neurone disease (MND) - the principle differential here (specifically the lower motor neurone progressive muscular atrophy form rather than the mixed upper/lower motor neurone ALS form). For exam purposes, the key difference between these two conditions is the nerve conduction studies. MMNCB shows conduction block. MND does not. MMNCB is a demyelinating condition, much in the same way Guillain Barré or chronic inflammatory demyelinating polyneuropathy (CIDP) are. However, in MMNCB this demyelination is in segments of a nerve rather than affecting the whole nerve. Therefore, the action potentials (as well as being slowed because of demyelination) actually don’t get past the areas of conduction block. The importance of doing nerve conduction studies is to decide whether a motor neuropathy is axonal (i.e. the axon itself getting damaged) or demyelinating. The demyelinating ones tend to be more easily and similarly treatable. MMNCB, Guillain Barré, and CIDP are all good examples of demyelinating neuropathies, all of which therefore respond to intravenous immunoglobulin (IVIG).
Note that the nerves involved in this particular case are the left radial nerve, right ulnar nerve, and right common perineal nerve.
Multifocal motor neuropathy
Acquired autoimmune demyelinating motor neuropathy
Associated with motor conduction block
Slowly progressive, distal motor neuropathy which progresses over many years
Anti-GM1 antibodies frequently raised
Usher’s syndrome
The leading cause of deafness and blindness .
Autosomal recessive condition and the blindness is due to Retinitis pigmentosa .
The different associations of Retinitis pigmentosa
Retinitis pigmentosa is the progressive degeneration of photoreceptor cells in the retina. It presents with peripheral vision loss and difficulty seeing in dim light (poor night vision as rod photoreceptors are affected first). There are lots of different mutations, and retinitis pigmentosa can be inherited in many different ways; autosomal dominant, autosomal recessive, X-linked and mitochondrial.
It can be associated with a number of rare such as:
Usher's syndrome associated deafness Refsum disease associated anosmia Kearns-Sayre syndrome associated ophthalmoplegia
Above continued
Retinitis pigmentosa
Retinitis pigmentosa primarily affects the peripheral retina resulting in tunnel vision
Features
night blindness is often the initial sign tunnel vision due to loss of the peripheral retina (occasionally referred to as funnel vision) fundoscopy: black bone spicule-shaped pigmentation in the peripheral retina, mottling of the retinal pigment epithelium
Associated diseases
Refsum disease: cerebellar ataxia, peripheral neuropathy, deafness, ichthyosis
Usher syndrome
abetalipoproteinemia
Lawrence-Moon-Biedl syndrome
Kearns-Sayre syndrome
Alport's syndrome
Solitary nodule monitoring
BTS guidelines for lung nodules:
Nodule <5mm, or clear benign features, or unsuitable for treatment: can be discharged Nodule =>8mm and high risk*: then CT-PET, and if CT-PET shows high uptake then biopsy Nodule 5-6mm, or =>8mm and low-risk*: then CT surveillance CT surveillance: if 5-6mm then at 1 year, if =>6 then in three months
When to use prasugrel or ticargrelor as per NICE guidelines
Most patients who’ve had an acute coronary syndrome are now given dual antiplatelet therapy (DAPT). Clopidogrel was previously the second antiplatelet of choice. Now ticagrelor and prasugrel (also ADP-receptor inhibitors) are more widely used. The NICE Clinical Knowledge Summaries now recommend:
post acute coronary syndrome (medically managed): add ticagrelor to aspirin, stop ticagrelor after 12 months post percutaneous coronary intervention: add prasugrel or ticagrelor to aspirin, stop the second antiplatelet after 12 months this 12 month period may be altered for people at a high-risk of bleeding or those who at high-risk of further ischaemic events
