MRCP UK

Acanthosis nigricans is a clinical sign strongly associated with insulin resistance.

It typically appears as:

Hyperpigmented
Thickened
Velvety plaques
Commonly in neck, axilla, groin

Why it happens

In insulin resistance:

↑ insulin levels (hyperinsulinemia)
Insulin acts on IGF-1 receptors in skin
This leads to keratinocyte and dermal fibroblast proliferation

Common associated conditions

Type 2 diabetes mellitus
Obesity
Polycystic o***y syndrome (PCOS)
Metabolic syndrome

𝗣𝗥𝗘𝗠𝗘𝗗𝗜𝗖𝗔𝗧𝗜𝗢𝗡 𝗥𝗘𝗚𝗜𝗠𝗘𝗡 𝗙𝗢𝗥 𝗜𝗢𝗗𝗜𝗡𝗔𝗧𝗘𝗗 𝗖𝗢𝗡𝗧𝗥𝗔𝗦𝗧 𝗔𝗟𝗟𝗘𝗥𝗚𝗬
(Prevention of contrast hypersensitivity reactions)

𝗘𝗟𝗘𝗖𝗧𝗜𝗩𝗘 / 𝗦𝗧𝗔𝗡𝗗𝗔𝗥𝗗 𝗣𝗥𝗘𝗠𝗘𝗗𝗜𝗖𝗔𝗧𝗜𝗢𝗡

Steroid options (choose one regimen):

• Methylprednisolone regimen (IV)
→ 40 mg IV at 4 hours before contrast
→ Repeat 40 mg IV at 1 hour before contrast

OR

• Hydrocortisone regimen (IV)
→ 200 mg IV at 5 hours before contrast
→ Repeat 200 mg IV at 1 hour before contrast

OR

• Prednisolone (oral option)
→ 50 mg PO at 13 hours before contrast
→ 50 mg PO at 7 hours before contrast
→ 50 mg PO at 1 hour before contrast

Antihistamine (all regimens)
• Diphenhydramine 25–50 mg IV/PO
→ Given 1 hour before contrast

𝗘𝗠𝗘𝗥𝗚𝗘𝗡𝗖𝗬 / 𝗥𝗔𝗣𝗜𝗗 𝗣𝗥𝗘𝗠𝗘𝗗𝗜𝗖𝗔𝗧𝗜𝗢𝗡
(When scan cannot be delayed)

Limited evidence if

𝗛𝗘𝗔𝗗𝗔𝗖𝗛𝗘 𝗥𝗘𝗗 𝗙𝗟𝗔𝗚𝗦
(SAH vs Migraine vs Temporal Arteritis )

𝗦𝗔𝗛 (Subarachnoid Hemorrhage)
Thunderclap Danger

Subarachnoid Hemorrhage

Classic Red Flags:
• Sudden “thunderclap” headache (peaks in 50
• Change in pattern
• Neurological deficit (NOT typical migraine)

𝗧𝗘𝗠𝗣𝗢𝗥𝗔𝗟 𝗔𝗥𝗧𝗘𝗥𝗜𝗧𝗜𝗦

Giant Cell Arteritis

High-Yield Red Flags:
• Age >50 years
• Temporal headache (localized, new type)
• Jaw claudication (very specific)
• Visual symptoms / transient vision loss
• Scalp tenderness (pain combing hair)
• Fever, fatigue, weight loss

Danger: Untreated → irreversible vision loss

Anti-Mi-2 Antibodies

Phenotype association:
Strongly associated with classic dermatomyositis skin and muscle phenotype, including:
– Heliotrope rash
– Gottron’s papules/sign
– Prominent photosensitive rash
– Marked proximal muscle weakness
– Often good response to therapy

Prevalence:
Anti-Mi-2 antibodies are found in approximately 10–20% of dermatomyositis (DM) cases

• Disease course and prognosis:
Generally associated with a favourable prognosis, including:
– Good response to corticosteroids and immunosuppression
– Lower risk of interstitial lung disease (ILD) compared to anti-MDA5 or antisynthetase syndrome
– Traditionally considered lower malignancy risk, though this is not zero (important nuance: malignancy risk is lower than TIF1-γ but still warrants age-appropriate screening)

Diagnostic implications

• Anti-Mi-2 is part of the myositis-specific antibody (MSA) panel used in suspected inflammatory myopathy.

• A positive anti-Mi-2 supports dermatomyositis diagnosis, especially in the presence of typical cutaneous features, but is not required for diagnosis.

• A negative result does not exclude DM, as many patients are antibody-negative or have other MSAs.

𝗠𝗢𝗬𝗔𝗠𝗢𝗬𝗔 𝗗𝗜𝗦𝗘𝗔𝗦𝗘 (𝗠𝗠𝗗)

A rare progressive cerebrovascular disease causing narrowing of major cerebral arteries with development of fragile collateral vessels.

Named “moyamoya” because angiography shows a classic “puff of smoke” appearance.

𝗣𝗮𝘁𝗵𝗼𝗽𝗵𝘆𝘀𝗶𝗼𝗹𝗼𝗴𝘆

Progressive stenosis affects:

• Distal internal carotid arteries (ICA)
• Proximal middle cerebral arteries (MCA)
• Proximal anterior cerebral arteries (ACA)

Compensatory fragile collateral vessels develop at the base of the brain.

These collaterals are:

• Fragile
• Inefficient for cerebral perfusion
• Prone to thrombosis and rupture

Result:

• Recurrent cerebral ischemia
• TIA / ischemic stroke
• Intracranial hemorrhage

𝗘𝗽𝗶𝗱𝗲𝗺𝗶𝗼𝗹𝗼𝗴𝘆

• More common in East Asians
• Female predominance
• Bimodal age distribution:

Children → 5–10 years
Adults → 30–50 years

𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗙𝗲𝗮𝘁𝘂𝗿𝗲𝘀

𝗖𝗵𝗶𝗹𝗱𝗿𝗲𝗻 → usually ischemic presentation

• Recurrent TIAs
• Ischemic stroke
• Seizures
• Headache
• Cognitive decline
• Weakness/paralysis

Symptoms may be precipitated by:

• Crying
• Hyperventilation
• Fever

𝗔𝗱𝘂𝗹𝘁𝘀 → often hemorrhagic presentation

• Intracerebral hemorrhage
• Subarachnoid hemorrhage
• Stroke symptoms
• Headache
• Cognitive impairment

𝗜𝗺𝗽𝗼𝗿𝘁𝗮𝗻𝘁 𝗔𝘀𝘀𝗼𝗰𝗶𝗮𝘁𝗶𝗼𝗻𝘀

May occur with:

• Down syndrome
• Neurofibromatosis type 1
• Sickle cell disease
• Prior cranial irradiation
• Autoimmune disease

When associated with another disorder → termed 𝗠𝗼𝘆𝗮𝗺𝗼𝘆𝗮 𝘀𝘆𝗻𝗱𝗿𝗼𝗺𝗲

𝗗𝗶𝗮𝗴𝗻𝗼𝘀𝗶𝘀

𝗠𝗥𝗜 𝗕𝗿𝗮𝗶𝗻

May show:

• Ischemic infarcts
• Chronic ischemic changes
• Intracranial hemorrhage

𝗠𝗥𝗔 / 𝗖𝗧 𝗔𝗻𝗴𝗶𝗼𝗴𝗿𝗮𝗽𝗵𝘆

Shows:

• ICA stenosis
• Abnormal collateral vessels

𝗚𝗼𝗹𝗱 𝗦𝘁𝗮𝗻𝗱𝗮𝗿𝗱 → Cerebral angiography

Classic finding:
“Puff of smoke” collateral network

𝗧𝗿𝗲𝗮𝘁𝗺𝗲𝗻𝘁

𝗠𝗲𝗱𝗶𝗰𝗮𝗹

Mainly for symptom prevention:

• Antiplatelet therapy (e.g. aspirin)
• Control vascular risk factors
• Adequate hydration
• Avoid hypotension

Medical therapy alone is often insufficient.

𝗗𝗲𝗳𝗶𝗻𝗶𝘁𝗶𝘃𝗲 𝗧𝗿𝗲𝗮𝘁𝗺𝗲𝗻𝘁 → Revascularization surgery

𝗗𝗶𝗿𝗲𝗰𝘁 𝗯𝘆𝗽𝗮𝘀𝘀

STA → MCA bypass

Provides immediate cerebral blood flow improvement.

𝗜𝗻𝗱𝗶𝗿𝗲𝗰𝘁 𝗯𝘆𝗽𝗮𝘀𝘀

Examples:

• EDAS
• EMS

Gradual development of new collateral circulation.

𝗖𝗼𝗺𝗽𝗹𝗶𝗰𝗮𝘁𝗶𝗼𝗻𝘀

• Recurrent stroke
• Intracranial hemorrhage
• Epilepsy
• Cognitive impairment

𝗕𝗟𝗢𝗢𝗗 𝗧𝗥𝗔𝗡𝗦𝗙𝗨𝗦𝗜𝗢𝗡 𝗜𝗡 𝗖𝗛𝗥𝗢𝗡𝗜𝗖 𝗞𝗜𝗗𝗡𝗘𝗬 𝗗𝗜𝗦𝗘𝗔𝗦𝗘 (𝗖𝗞𝗗)

𝗔𝘀𝘀𝗲𝘀𝘀 𝗛𝗲𝗺𝗼𝗱𝘆𝗻𝗮𝗺𝗶𝗰 𝗦𝘁𝗮𝘁𝘂𝘀

• Hemodynamically unstable
(e.g., acute hemorrhage, shock, symptomatic severe anemia)
Transfuse packed red blood cells (PRBCs)

• Hemodynamically stable: Measure hemoglobin (Hb)

𝗛𝗲𝗺𝗼𝗴𝗹𝗼𝗯𝗶𝗻-𝗕𝗮𝘀𝗲𝗱 𝗗𝗲𝗰𝗶𝘀𝗶𝗼𝗻

• Hb < 7 g/dL: Consider transfusion
• Hb ≥ 7 g/dL: Usually avoid transfusion and monitor clinically

Higher transfusion thresholds may be considered in:
• Active ischemia / ACS
• Symptomatic anemia
• Ongoing bleeding
• Severe hypoxia
• Hemodynamic compromise

𝗜𝗺𝗺𝗲𝗱𝗶𝗮𝘁𝗲 𝗥𝗶𝘀𝗸𝘀 𝗼𝗳 𝗧𝗿𝗮𝗻𝘀𝗳𝘂𝘀𝗶𝗼𝗻

Hyperkalemia (↑ K⁺)
Transfusion-associated circulatory overload (TACO)
Acute hemolytic reactions
Febrile or allergic reactions
TRALI (rare)

𝗟𝗼𝗻𝗴-𝗧𝗲𝗿𝗺 𝗥𝗶𝘀𝗸𝘀 𝗶𝗻 𝗖𝗞𝗗

Iron overload with repeated transfusions
HLA alloimmunization
(important in future renal transplant candidates)
Delayed hemolytic reactions
Very low infection transmission risk

In stable CKD anemia:
Prefer iron replacement ± ESA therapy
Avoid unnecessary transfusions due to sensitization risk before kidney transplantation

𝗟𝗮𝗺𝗯𝗲𝗿𝘁 𝗘𝗮𝘁𝗼𝗻 𝗠𝘆𝗮𝘀𝘁𝗵𝗲𝗻𝗶𝗰 𝗦𝘆𝗻𝗱𝗿𝗼𝗺𝗲 (𝗟𝗘𝗠𝗦)

𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺

• Autoantibodies against presynaptic voltage-gated calcium channels (VGCC)
• ↓ acetylcholine release

𝗖𝗹𝗮𝘀𝘀𝗶𝗰 𝗖𝗹𝘂𝗲𝘀

• Weakness improves with repeated use
• Proximal leg weakness prominent
• Difficulty climbing stairs / rising from chair

𝗥𝗲𝗳𝗹𝗲𝘅𝗲𝘀

• Reduced or absent
• May improve after exercise

𝗔𝘂𝘁𝗼𝗻𝗼𝗺𝗶𝗰 𝗦𝘆𝗺𝗽𝘁𝗼𝗺𝘀

Common:
• Dry mouth
• Erectile dysfunction
• Constipation
• Orthostatic hypotension

𝗔𝘀𝘀𝗼𝗰𝗶𝗮𝘁𝗶𝗼𝗻

• Strongly associated with small-cell lung cancer (SCLC)

𝗗𝗶𝗮𝗴𝗻𝗼𝘀𝗶𝘀

• VGCC antibodies
• Repetitive nerve stimulation:

* Incremental response after exercise

𝗧𝗿𝗲𝗮𝘁𝗺𝗲𝗻𝘁

• Treat underlying malignancy
• Amifampridine (3,4-DAP)
• Pyridostigmine sometimes helps
• Immunotherapy in autoimmune disease

𝗠𝘆𝗮𝘀𝘁𝗵𝗲𝗻𝗶𝗮 𝗚𝗿𝗮𝘃𝗶𝘀 (𝗠𝗚) MG = fatigable weakness + ocular symptoms + normal reflexes+ 𝗔𝘂𝘁𝗼𝗻𝗼𝗺𝗶𝗰 𝗦𝘆𝗺𝗽𝘁𝗼𝗺𝘀 usually absent

𝗟𝗮𝗺𝗯𝗲𝗿𝘁–𝗘𝗮𝘁𝗼𝗻 𝗠𝘆𝗮𝘀𝘁𝗵𝗲𝗻𝗶𝗰 𝗦𝘆𝗻𝗱𝗿𝗼𝗺𝗲 (𝗟𝗘𝗠𝗦) LEMS = proximal weakness + autonomic symptoms + absent reflexes + SCLC

Stroke Thrombolysis Window

The thrombolysis window refers to the time period in which IV clot-dissolving therapy (Alteplase) can be safely and effectively administered in acute ischemic stroke.

Ischemic Stroke – IV Thrombolysis

Standard window:
• Within 4.5 hours from symptom onset

Best outcome window:
• Within 3 hours → maximal neurological recovery benefit

Extended window (selected patients):
• Up to 9 hours OR unknown onset (e.g., wake-up stroke)
• Requires advanced imaging (MRI / CT perfusion) to confirm salvageable brain tissue

Mechanical Thrombectomy (Large Vessel Occlusion)

Routine window:
• Up to 6 hours from onset

Extended window (selected cases):
• Up to 24 hours
• Based on imaging selection (penumbra vs infarct core mismatch)