Mucocutaneous leishmaniasis

- caused by L.b.braziliensis
- indurated or ulcerating lesions affecting mucosa or cartilage typically on lips or nose (espundia)
- diagnosis by culture of parasite or PCR
- treatment: sodium stibogluconate

Malignant melanoma

Clinical criteria for diagnosis (ABCDE)

A: Asymmetry of mole
B: Border irregularity
C: Colour variegation
D: Diameter more than 6mm
E: Evolving lesion with changes over time



Clarke's level (reflects level of invasion through dermis)
I : not invaded pass basement membrane
II: involvement of superficial dermis
III: involvement of deep dermis
IV: involvement of subcutis

Breslow's thickness

Tumor Depth	Approximate 5 year survival
<1 mm	95-100%
1 - 2 mm	80-96%
2.1 - 4 mm	60-75%
>4 mm	50%

Katayama fever

- acute schistosomiasis
- occurs 6 weeks to 3 months after initial infection especially by S.mansoni and S.japonicum
- snail vectors release cercariae that penetrates skin causing itchy papular rashes. Cercariae shed their tails to become schistosomules and migrate via lungs to liver.
- presents with fever, rash, myalgia, diarrhea, hepatosplenomegaly and pneumonitis
- diagnosis by serology and rectal biopsy (look for eggs)
- treatment: praziquantel

Blotting methods

Southern blot : DNA analysis (detection of specific DNA sequence)
Northern blot : RNA analysis
Western blot :  Protein analysis
Eastern blot : Protein post translational modification analysis (eg: lipids and glycoconjugate)
Southwestern blot : DNA binding protein analysis

Erosive osteoarthritis

- A form of OA marked by greater degree of inflammation and characterised by presence of erosions on plain radiograph
- predominantly affects postmenopausal women
- classically affects PIPJ and DIPJ
- gull's wing or inverted T pattern of erosion is typical
- commonly confused with RA, but there is no juxtaarticular osteoporosis

G protein

- located in cytoplasm
- coupled to transmembrane receptor (G protein coupled receptor) - seven helical membrane receptors
- ligand binding site is exposed outside surface of cell. Many ligands binds to GPCR, such as TSH, ACTH, serotonin and GABA
- Ligand binding initiates secondary messenger - cAMP or IP3
- best described human disease caused by mutation of G protein is pseudohypoparathyroidism (Albright's hereditary osteodystrophy)

Alport's syndrome

- combination of nephritis and sensorineural deafness
- X-linked
- autosomal recessive/dominant form cause renal disease without deafness or lenticonus
- males are affected more severely
- mutation of COL4A5 gene (80%), on X chromosome
- caused by abnormality in type IV collagen (alpha 5 chain)
- microsopic hematuria during first decade of life
- may present with acute macroscopic hematurie post URTI
- association: anterior lenticonus, retinopathy, posterior corneal dystrophy, bilateral dot fleck marks around fovea
- diagnosis is by renal biopsy

Toxic shock syndrome

- associated with tampon use in menstruating women and surgical wound infection
- caused by Staph.aureus (producing TSST-1) or Strep.pyogenes
- presents with fever, diffuse macular rash over palm and soles (followed by desquamation after 1-2 week), hypotension, multiorgan failure
- treatment: flucloxacillin + clindamycin
- although clindamycin is a bacteriostatic antibiotic, it acts by switching off protein synthesis within bacteria which lead to decreased exotoxin expression thereby removing mediators of TSS

Q fever

- zoonotic disease caused by Coxiella burnetti
- this organism is very resistant to drying and inhaled from infected dust
- cattle, sheep and goats are primary reservoir
- sudden onset of high fever, severe headache, malaise, confusion, sore throat, chills, sweat, non productive cough, nausea and vomiting, diarrhea, abdominal pain and chest pain
- a cause of culture negative endocarditis
- majority has abnormal liver function test 
-  diagnosis: serology for Coxiella burnetti or complement fixation 
- treatment: doxycycline

Chronic fatigue syndrome

- a.k.a myalgic encephalomyelitis

- occurs most commonly in women between ages 20 and 50 years

- can be trigerred by viral infection

- cardinal symptom is chronic fatigue made worse by minimal exertion

- poor concentration, impaired memory, insomnia/hypersomnia, muscular pain

- management: graded exercise therapy to combat deconditioning and cognitive behavioral therapy

Adverse drug reaction (ADR)

Types
A (Augmented) : dose dependent and predictable, can occur to anyone
B (Bizarre) : dose independent and unpredictable
C (continuous or chronic) : prolonged drug use (eg: analgesic nephropathy)
D (delayed) : teratogenic or carcinogenic
E (end of use) : withdrawal phenomena after drug is stopped

Basic statistic (2)

OR = (38/25) / (69/129) = 2.84

Coal worker pneumoconiosis

- related to total coal dust exposure
- simple CWP characterised by small rounded opacities (<1.5mm) on chest X-ray, and is associated with emphysema. Asymptomatic
- Progressive massive fibrosis (PMF)
    - development of larger opacities (>3mm)
    - lesion usually in upper zone
    - ANA and RF often positive
    - mixed restrictive and obstructive lung defect with reduced transfer factor
    - presents with melanoptysis
- Caplan syndrome = pneumoconiosis + rheumatoid arthritis
    - manifest as multiple round pulmonary nodules

Autoimmune polyendocrine syndrome

Type 1
- autosomal recessive, rare
- mutation of AIRE gene on chromosome 21
- hypoparathyroidism, addison's disease, chronic mucocutaneous candidiasis
- other associations : hypogonadism, pernicious anemia, hypothyroidism, vitiligo, alopecia, chronic active hepatitis

Type 2 (Schmidt's syndrome)
- Addison's disease, type 1 DM, autoimmune thyroid disease
- other associations: hypogonadism, vitiligo, alopecia, pernicious anemia, chronic active hepatitis, atrophic gastritis, coeliac disease, dermatitis herpetiformis

Wernicke's encephalopathy

- acute neuropsychiatric reaction to severe thiamine deficiency
- characterised by nystagmus, abducens and conjugate gaze palsy, ataxia, global confusion state
- neuronal loss in mamillary bodies
- causes: alcoholism, carcinoma of stomach, pregnancy
- treatment: IV thiamine

Phaeochromocytoma

- associated with MEN II , Sturge Weber syndrome and von Hippel Lindau syndrome
- presents with hypertension, headache, palpitation, excessive sweating, anxiety
- symptoms are precipitated by sneezing, stress, surgery, cheese, alcohol, TCA
- rule of 10 - 10% extra-adrenal, 10% bilateral, 10% malignant, 10% familial, 10% not associated with hypertension
- familial phaeochromocytoma almost always arise from adrenal medulla
- adrenal medulla has cells that contain phenylethanolamine-N-methyltransferase that converts norepinephrine to epinephrine. This enzyme is lacking in other sympathetic ganglia.
- diagnosis by raised urinary catecholamines over 24 hours and MIBG (metaiodobenzylguanidine) scan of adrenals
- treatment for hypertension is with alpha-blockade (phenoxybenzamine) prior to beta-blockade

Acute tubular necrosis

- usually arises following an acute ischemia or nephrotoxic event
- characterised by 3 phases
  i) initiation phase: acute decrease in GFR with sudden rise in creatinine
  ii) maintenance phase: sustained marked reduction in GFR
  iii) recovery phase: tubular function gradually restored with concomittant reduction in creatinine
- pigmented 'muddy brown' granular cast are characteristic of ATN and depict sloughed tubular epithelial cells
- reduced urinary osmolality < 350mOsm/kg (reduced tubular function and reduced filtration rate)
- raised urinary sodium concentration > 40mmol/L (decreased tubular reabsorption of sodium)
- associated with accelerated hypertension, hypotension, diabetes, liver failure, eclampsia, aminoglycosides.

Renal tubular acidosis

Type I RTA (distal)
- defect in excretion of acid
- associated with hypergammaglobulinemia, amphotericin B, primary biliary cirrhosis and thyroiditis
- presents with hypokalemia, acidosis and low urinary ammonium production
- inability to lower urine pH below 5.3 despite systemic acidosis
- low urinary citrate and hypercalciuria, causing nephrocalcinosis, renal stone, rickets and osteomalacia (calcium loss and buffering of retained H+ in bone)
- diagnosis: acid load (oral ammonium chloride is given - failure to lower urine pH)
- treatment: oral sodium bicarbonate or citrate

Type II RTA (proximal)
- defect in absorption of bicarbonate
- Fanconi syndrome and osteomalacia occurs
- cardinal features are acidosis, hypokalemia and hypophosphatemia
- apperance of bicarbonate in urine
- urine can be acidified
- expired tetracycline use and Wilson disease is a cause
- diagnosis: IV sodium bicarbonate load (high fractional excretion of bicarbonate)
- treatment: high dose of bicarbonate

Type IV RTA (hyporeninemic hypoaldosteronism)
- commonest RTA
- occurs in diabetes and tubulointerstitial disease
- associated with chronic ingestion of NSAIDs
- cardinal feature is hyperkalemia
- fludrocortisone treatment is effective


Note: osteomalacia can occur in both type I and II
- type III RTA is a rare combination of type I and II

Pemphigus vulgaris

- chronic blistering skin disease
- painful but rarely pruritic
- mucosal involvement with ulceration
- flaccid blister, especially on trunk
- positive Nikolsky sign
- skin biopsy: superficial intraepidermal split (between keratinocyte and basement membrane)
    - whereas in bullous pemphigoid : subepidermal (between epidermis and dermis)
- antibodies to desmosomal protein 3 (desmoglein 3)
- treatment: high dose steroid

Basal cell carcinoma

- commonest skin cancer
- seen most commonly on face of elderly patient
- predisposing factors: prolonged sun exposure, radiation, chronic scarring, Gorlin syndrome
- nodular BCC is commonest
- characteristic pearly-white raised border
- treatment: excision surgery

Gerstmann's syndrome

- lesion in dominant (left) parietal lobe (angular gyrus)

"RAAF"

R - right left confusion
A - agraphia
A - acalculia
F - finger agnosis



Right sided parietal lobe lesions causes anosognosia.

J wave

- most characteristic of moderate to severe hypothermia
- best seen in left chest leads and are described as a dome or hump in the terminal portion of QRS complex
- size of J wave correlated with degree of hypothermia

Primary sclerosing cholangitis

- disorder of unknown cause characterised by non malignant non bacterial inflammation, fibrosis, and stricture of the intra and extrahepatic bile ducts
- associated with ulcerative colitis
- more common in men (70%) and average age of 40
- presents with fluctuating jaundice, pruritus and cholangitis
- positive p ANCA
- raised ALP initially followed by raised bilirubin, hypergammaglobulinaemia
- ERCP: multiple strictures in biliary system
- cholangiogram: intrahepatic and extrahepatic duct strictures ('beaded' appearance)
- 10% risk of cholangiocarcinoma
- treatment: ursodeoxycholic acid, liver transplantation (only proven long term treatment)

Retinitis pigmentosa

- characterised by triad of
   - night blindness (loss of rod function)
   - tunnel vision (rod dysfunction)
   - pigmented 'bony spicules'

Important systemic associations
- Abetalipoproteinemia (Bassen Kornzweig syndrome)
- Refsum's disease
- Usher syndrome
- Laurence Moon Biedl syndrome
- Kearns Sayre syndrome

Giardiasis

- caused by protozoon Giardia lamblia
- a cause of traveller's diarrhea
- transmitted by ingestion of cyst
- presents with diarrhea associated with malabsorption, steatorrhea, nausea, cramps, abdominal pain, bloating.
- diagnosis: stool microscopy for cyst; trophozoite seen on biopsy of small bowel mucosa
- treatment: metronidazole 2g daily for 3 days

Whipple disease

- extremely rare systemic infectious disease caused by Trophyrema whippeli (actinomycetes)
- affects middle aged while males
- presents with arthralgia/arthritis (seronegative arthropathy ~70%), diarrhea (70%), abdominal pain, fever and skin darkening
- severe malabsorption results in weight loss (90%) and along with fatigue and weakness caused by anemia
- also heart, lung, eye and brain involvement
- oculomasticatory myorrhythmia is characteristic
- small bowel (jejunal) biopsy: PAS positive macrophages in lamina propria
- most lesions (except cerebral) are reversible on prolonged antibiotic therapy
- treatment: amoxicillin, tetracycline, cotrimoxazole for 1 year

Multiple endocrine neoplasia

- autosomal dominant
- MEN-1 gene is a tumor suppressor gene producing menin (chromosome 11)
- MEN-2 gene is ret proto-oncogen (receptor tyrosine kinase)

MEN-1 (Wermer's syndrome)      "PPP" 
- Parathyroid hyperplasia/adenoma
- Pancreas endocrine tumor (gastrinoma, insulinoma, somatostatinoma, VIPoma, glucagonoma)
- Pituitary prolactinoma or GH secreting tumor

MEN-2A (Sipple syndrome)          "TAP"
- Thyroid (medullary thyroid carcinoma)
- Adrenal (phaeochromocytoma)
- Parathyroid hyperplasia

MEN-2B
- similar to MEN-2A, but parathyroid hyperplasia is rare
- plus mucosal neuroma and Marfanoid appearance

Paroxysmal nocturnal hemoglobinuria

- a.k.a Marchiafava Micheli syndrome
- somatic mutation in the phosphatidylinositol glycan-A gene on X chromosome
- aplastic anemia like syndrome in which red cells are predisposed to complement lysis causing hemolytic anemia
- deficient GPI (glycophosphatidylinositol) anchored membrane proteins (CD55, CD59)
- presents with hemoglobinuria and venous thrombosis (eg:Budd Chiari thrombosis)
- immunophenotyping : absence of CD55 (decay accelerating factor) /CD59 (membrane inhibitor or reactive lysis)
- HAM test or flow cytometric evaluation of blood is diagnostic test.
- treatment: plasma reduced washed red cells (correct anemia), warfarin, eculizumab (new monoclonal antibody which inhibit complement system)
- significant proportion of patient go on to develop aplastic anemia or acute leukemia

Wiskott Aldrich syndrome

- X linked recessive
- mutation in WASP gene
- triad of pyogenic infection, eczema and thrombocytopenia
- due to lack of sialophorin, produces low IgM levels and impaired cell mediated immunity

Hemochromatosis

- autosomal recessive
- commonest mutation is C282Y, in chromosome 6, affecting HFE gene
- most common single gene disorder in caucasians (carrier frequency 1 in 10)
- serum iron is elevated (>300mg/dL)
- serum transferrin saturation > 50% (most sensitive biochemical marker of iron overload)
- serum ferritin increased
- urinary iron excretion markedly increased (>2mg/24hour) by chelating drug desferioxamine
- diagnosis confirmed by DNA analysis
- presents with skin pigmentation (iron deposition stimulates increase melanin production), hepatic dysfunction, diabetes (bronze diabetes), hypogonadism, arthropathy (pseudogout), restrictive cardiomyopathy
- treatment: regular venesection (monitor by serum ferritin) - cardiomyopathy may improve with venesection

Syringomyelia

- intrinsic cord lesion as cyst expands out
- symptoms develop between 20-30 years
- most commonly at cervical and upper thoracic level, but sometimes extending into the medulla
- 90% have type 1 Arnold Chiari malformation
- cardinal sign is dissociative sensory loss (absent pain and temperature sensation; preserved light touch, vibration and joint position)
- pain is exacerbated by coughing and exertion in upper limbs
- "UMN sign in lower limb, LMN sign in upper limb"
- other signs: sensory loss, wasting of small hand muscles, Horner's syndrome, limb hemihypertrophy, syringobulbia, Charcot's joint

Gonococcal arthritis

- commonest cause of septic arthritis in previously young fit adult
- more common in females and homosexual men
- presents with fever, characteristic rash/pustules, polyarthralgia and tenosynovitis, followed by large joint monoarticular arthritis.
- treatment: IV ceftriaxone, examination of joint and washout under anaesthesia

Retroperitoneal fibrosis

- a.k.a Ormond's disease
- more common in males and peak in 5th or 6th decade of life
- one of the multifocal fibrosclerotic syndrome (which involves mediastinal fibrosis, sclerosing cholangitis and Riedel thyroiditis)
- presents with low back pain (commonest), malaise, anemia, uremia (ureteric obstruction), raised ESR
- 2/3 idiopathic, associated with malignancy, drug (methysergide, practolol), radiotherapy, untreated AAA, SLE, scleroderma, carcinoid syndrome
- CT is best diagnostic modality
- treatment: steroid, azathioprine

Wegener's granulomatosis

- granulomatous necrotizing vasculitis
- triad of
  i) upper airways (granuloma) - rhintis (first sign), epistaxis, sinusitis, saddle nose (perforated septum), otitis, mastoiditis
  ii) lungs (granuloma and vasculitis) - multiple pulmonary nodule (coin lesions), cavitating lesion with diffuse alveolar changes, presents with hemoptysis
  iii) renal (vasculitis)- segmental crescentric necrotizing glomerulonephritis
- c-ANCA (PR3) positive (highly sensitive and specific)
- treatment: IV methylprednisolone, cyclophosphamide





Poor prognostic indicators
- presence and severity of renal involvement
- elderly
- pulmonary hemorrhage
- poor response to therapy at 2 weeks
- high degree of sclerosed glomeruli/interstitial scarring on biopsy

Count down to MRCP part 1

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Mitral valve prolapse (MVP)

- posterior bulging of leaflets of mitral valve in systole
- occurs in 5% of population, usually female with narrow AP chest diameter
- presents with chest pain, palpitation or fatigue
- association: Marfan's syndrome, ASD, pseudoxanthoma elasticum, Ehler's Danlos syndrome, WPW syndrome, HCM, SLE, autoimmune thyroid disease
- mid to late systolic click and murmur (squatting increase click, standing increase murmur)
- myxomatous degeneration and redundant valve tissue due to deposition of acid mucopolysaccharide material
- sequelae (less than 1% per year): embolic phenomena, rupture of mitral valve chordae, risk of endocarditis, prolonged QT, sudden death
- treat with beta blocker if there is symptoms of dysautonomia (eg: palpitation, chest pain)

Sick sinus syndrome

- a.k.a tachy-brady syndrome
- fibrosis or fatty infiltration of sinus node, AV node, bundles of His or its branches
- characterised by periods of sinus bradycardia, sinus arrest, a combination of sinoatrial or atrioventricular conduction defect and supraventricular tachycardia
- presents with light-headedness, palpitation, syncope or stroke.
- treatment: permanent dual chamber pacemaker (single chamber pacing is associated with pacemaker syndrome)
- if patient is on beta blocker, reduce to dose slowly instead of stopping completely to avoid rebound tachycardia

Palmar crease xanthoma

- pathognomonic of type III hyperlipidemia (Broad beta disease / remnant hyperlipidemia / familial dysbetalipoproteinemia) - autosomal recessive
- caused by deficiency of apoliproprotein E (ligand for chylomicron)
- characterised by increased LDL, triglyceride and cholesterol, decreased HDL
- have elevation of IDL, a VLDL remnant
- diagnosed by lipoprotein electrophoresis or genotyping of apoprotein E
- also presents with tuboeruptive xanthoma

Wilson's disease

- toxic accumulation of copper in the liver and CNS (basal ganglia) due to failure of biliary copper excretion
- autosomal recessive
- defective gene ATP 7B (chromosome 13)
- prevalence 3:100,000
- normal copper absorption but defetive intrahepatic formation of caeruloplasmin
- features
   - onset in childhood/adolescence
   - hepatic dysfunction (cirrhosis)
   - CNS involvement (chorea, oromandibular dystonia, tremor, seizure, cerebellar signs, psychosis)
   - Kayser-Fleischer ring (copper deposition in Descement membrane)
   - hemolysis
   - Fanconi syndrome
   - low serum uric acid
- diagnosis
   - decrease in serum caeruloplasmin
   - increase in hepatic copper content
   - increase urinary excretion of copper (further increase following administration of penicillamine)
- treatment: copper chelators (penicillamine and trientine), zinc

Mitochondrial inheritance

- maternal in origin
- both sexes can be affected

Examples
- Leber's optic atrophy
- MELAS (mitochondrial encephalopathy + lactic acidosis + stroke)
- MERRF (myoclonic epilepsy with ragged red fibre)
- Kearns-Sayre syndrome (oculocraniosomatic disease)
- progressive external ophthalmoplegia
- Pearson syndrome (lactic acidosis + pancreatic insufficiency + pancytopenia)
- some deafness
- some familial diabetes mellitus

Basic statistic (1)

Data
- Qualitative
   Nominal : ABO blood group, male/female, dead/alive
   Ordinal  : mild/moderate/severe
- Quantitative
   Numerical discrete : number of death per year
   Numerical continuous: age, weight, blood pressure


Sensitivity
- probability that a test will be positive when a patient has the condition (TP / TP+FN)


Specificity
- probability that a test will be negative when a patient does not have the condition (TN / TN+FP)
- if threshold for screening is increased, specificity will increase


Positive predictive value
- probability that if a test is positive, it is true (TP/ TP+FP)


Negative predictive value
-  probability that if a test is negative, it is true (TN / TN+FN)


   The higher prevalence will have greater PPV and lower NPV

activated charcoal

- mechanism of action
  i) binding of toxin to prevent stomach or intestinal absorption.
  ii) interrupt enterohepatic or enteroenteric circulation of some drugs/toxins and their metabolites


Contraindications "CHEMICAL"

C: Cyanide
H: Hydrocarbon
E: Ehtanol
M: Metals
I: Iron
C: Caustic/corrisives (acid/alkali)
A: Airway unprotected
L: Lithium

Pseudomembranous colitis

- acute exudative infection of colon caused by Clostridium difficile
- Clostridium difficile produce 2 types of toxin: type A is enterotoxin, type B is cytotoxic
- risk factor: antibiotic treatment (including clindamycin, ciprofloxacin, ampicillin, amoxicillin, cephalosporin)
- Greatest risk = ciprofloxacin
- symptoms varies from mild self limiting diarrhea to acute fulminating toxic megacolon
- tissue culture, ELISA and PCR help detect C.difficile toxin (CDT)
- treatment: stop the antibiotic, metronidazole or oral vancomycin

Drugs causing gynaecomastia

" DISCO"

D: Digoxin
I: Isoniazide
S: Spirinolactone
C: Cimetidine
O: Omeprazole / Oestrogen

Drugs removed by hemodialysis / hemoperfusion

Hemodialysis "BLAMES"

B: barbiturates
L: lithium
A: alcohol
M: methanol
E: ethylene glycol
S: salicylate

Charcoal hemoperfusion
- paracetamol
- theophylline

SIADH inducing drugs

"ABCD"

A: analgesia (opioids, NSAIDs)
B: barbiturates
C: carbamazepine, cyclophosphamide, chlorpromazine
D: diuretics (thiazide)

other medications: vincristine, vinblastine, etc

- democlocycline can induce nephrogenic DI and thus can be used to treat SIADH

- criteria for diagnosis of SIADH includes normal renal, adrenal and thyroid function with hyponatraemia and hypotonic plasma (<270mOsmol/kg)

Xeroderma pigmentosum

- autosomal recessive
- defect in nucleotide excision repair, leading to deficient repair of DNA damage by UV radiation and chromosome breakage (uv light cause formation of pyrimidine dimer and prevent enzyme DNA polymerase from replicating DNA strand beyond site of dimer formation)
- photosensitivity with severe sunburn
- suffer from multiple malignant cutaneous neoplasm at early age

von Hippel Lindau disease

- autosomal dominant
- mutation in VHL gene (chromosome 3)
- features
   - cerebellar, brainstem and spinal hemangioblastoma
   - retinal angioma
   - phaeochromocytoma / paraganglioma
   - clear cell renal cell carcinoma (most common cause of death)
- genetic testing (VHL gene analysis) in affected families should take place around 5 years of age
- affected individual requires yearly urinalysis, catecholamine screening, fluorescein angiography and 3 yearly brain MRI screening

CADASIL

- CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy
- most common genetic form of vascular dementia, usually presents in middle age
- thalami and basal ganglia are usually involved
- characterised by migraine with aura, stroke at young age and early vascular dementia
- affected gene : NOTCH 3 gene (chromosome 19)
- MRI: leucoaraiosis and infarction, T2 weighted hyperintensity of periventricular white matter
- diagnosis is by skin biopsy
- neuropathological studies show pathognomonic granular osmiophilic materials in media of small arteries

Subacute combined degeneration of cord

- a.k.a Lichtheim disease
- due to vitamin B12 (cobalamin) deficiency, usually associated with pernicious anemia
- associated with chronic nitrous oxide exposure (interfere with methionine synthetase)
- causes classic combination of slowly evolving spastic paraparesis (long tract sign), peripheral neuropathy (absent ankle jerk) and posterior column cord damage (loss of vibration sense and propioception)
- presents with weakness of legs, arms, trunk, tingling and numbness, memory problems, decreased visual acuity (optic neuritis)
- serum B12 less than 100pg/ml and increased level of methyl malonic acid and homocysteine
- MRI: increased T2-weighted signal in posterior column



Differential diagnosis of absent ankle jerk (LMN lesion) + extensor plantar (UMN lesion)
- subacute combined degeneration of cord
- motor neurone disease
- tabes dorsalis (syphilis)
- Friedriech's ataxia
- lesion of cauda equina
- diabetes with CVA
- anterior spinal artery thrombosis affects corticospinal tracts and spinothalamic tracts
- cerebrotendinous xanthomatosis (dementia, gait ataxia, loss of vibration sense, cataracts, tendon xanthoma)

Weber's syndrome

- ipsilateral 3rd nerve palsy with contralateral hemiparesis
- unilateral infarct in midbrain (ventral lesion) due to occlusion of branch of basilar artery



Other 3rd nerve brainstem syndrome
Nothnagel's syndrome = 3rd nerve palsy + cerebellar ataxia
Benedikt's syndrome = 3rd nerve palsy + contralateral hemitremor
Claude's syndrome = 3rd nerve palsy + cerebellar ataxia + hemitremor

sporadic cJD

- affects older age (peak incidence 7th decade), as opposed to variant cJD (younger age)
- presents with rapidly progressive dementia with associated neurological signs (cerebellar ataxia and visual dysfunction)
- myoclonic jerks are characteristic
- typical EEG changes (1Hz periodic discharge)
- positive CSF result for 14-3-3 protein
- progression to akinetic mute state followed by death (2/3 die within 6 months)

Herpes simplex encephalitis

- caused by HSV-1 in 90% cases
- temporal lobe changes on neuroimaging is typical (lesions are often hemorrhagic)
- diagnosis is by CSF PCR for HSV
- treatment: IV aciclovir

Mycobacterium avium intracellulare

- saprophytic organism of low pathogenicity and ubiquitous in soil and water
- occurs in later stage of HIV infection when patient are profoundly immunosuppressed
- presents with fever, malaise, weight loss, anorexia, anemia (dissemination to bone marrow), diarrhea and malabsorption, generalised lymphadenopathy, tender hepatosplenomegaly
- in immunocompetent person, it causes pulmonary infection (Lady Windermere syndrome)
- diagnosis: culture from blood or bone marrow
- primary prophylaxis with azithromycin when CD4 count less than 50
- treatment: ethambutol, rifabutin and clarithromycin

Yellow fever

- caused by flavivirus
- confined in Africa and South America
- transmitted by A.africanus (Africa) and Haemagogus (America)
- severe flu like illness with high grade fever, epigastric discomfort, relative bradycardia (Faget's sign) followed by an apparent recovery
- following the apparent recovery, patient develops high fever, jaundice, hepatomegaly, ecchymosis, gum bleeding, hematemesis and melena.
- mortality up to 40%
- treatment: supportive

Live vaccine

Live vaccines (to be avoided in immunocompromised patient)

" MMR BOY"

MMR : measles, mumps, rubella
B : BCG
O : oral polio (Sabin), oral typhoid
Y: yellow fever

Anthrax

- caused by gram positive aerobic bacillus - Bacillus anthracis
- cutaneous anthrax (most common form) commonly causes a painless, black indurated eschar (without pus), associated with marked edema
- mortality from cutaneous disease is 20%, whereas 90% for inhalational antrax is untreated
- gastrointestinal anthrax is due to consumption of undercooked, contaminated meat, can present with GI bleeds
- diagnosis: smear from cutaneous lesion or serological confirmation
- inhalational anthrax is associated with a poor yield from sputum culture with greatest yield from blood culture.
- treatment: ciprofloxacin, or doxycycline + clindamycin

Brucellosis

- a.k.a Malta fever
- zoonosis caused by gram negative coccobacilli which spread through untreated milk (infected cattle or goats) and raw beef
- symptoms are non specific with fever, malaise, arthralgia and depression
- hepatosplenomegaly is present
- causes spondylitis / sacro-ilitis
- leukopenia is common
- detection of brucella requires prolonged blood culture (up to 6 weeks)
- Brucella agglutination test helps confirm diagnosis
- treatment: doxycycline, rifampicin and gentamicin/cotrimoxazole for 6 weeks

Myocarditis

- Causes are Coxsackie or adenoviral infection, Trypanosoma cruzi, Streptococcus (rheumatic carditis), diphtheria, toxoplasmosis, Lyme disease, toxins and autoimmune conditions
- presents with fatigue, palpitations, chest pain, dyspnea and fulminant congestive heart failure
- ECG: ST and T wave abnormalities and arrhythmias. Heart block in diphtheritic myocarditis, Lyme disease and Chagas disease
- cardiac enzymes elevated
- treatment: identify and treat underlying cause, bed rest and treatment for heart failure. Often resolves completely