Transient Ischemic Attack (TIA) - Complete MBBS Intern Guide

1. Definition (The Modern Tissue-Based Definition)

"A TIA is defined as transient neurologic dysfunction caused by focal ischemia of brain tissue, spinal cord, or retina without acute infarction."

• Frameworks for Internal Medicine

"Patients with symptoms less than 24 hours can have representative ischemic lesions on diffusion-weighted or perfusion-weighted MRI, so TIA has moved from time-based to tissue-based definition."

• Rosen's Emergency Medicine

2. Pathophysiology & Mechanisms

"It has been realized that many TIAs previously attributed to atherothrombosis are truly embolic strokes that leave a trace of infarction but have resolved clinically."

• Adams & Victor's Principles of Neurology

3. Clinical Features

Anterior Circulation (Carotid territory) TIA:

• Hemiparesis / hemiplegia (contralateral)
• Hemisensory loss (contralateral face, arm, leg)
• Aphasia (if dominant hemisphere)
• Amaurosis fugax - transient monocular blindness ("curtain coming down"), from ophthalmic artery (branch of ICA)

Posterior Circulation (Vertebrobasilar) TIA:

• Diplopia, dysarthria, dysphagia
• Vertigo + ataxia (cerebellar)
• Crossed deficits (ipsilateral cranial nerve + contralateral limb weakness)
• Drop attacks (sudden loss of postural tone without LOC)
• Bilateral visual field defects

"TIAs may present as transient spells of hemiparesis, aphasia, numbness or tingling on one side, dysarthria, diplopia, ataxia, obscuration of a visual field, or combinations thereof that replicate the stroke syndromes. Even limb shaking can represent a TIA."

• Adams & Victor's Principles of Neurology

4. Risk of Subsequent Stroke (Why TIA is a Neurological Emergency)

• Up to 10% stroke risk within 2 days
• Up to 15% stroke risk at 90 days (Frameworks for Internal Medicine)
• ~6% of strokes after TIA occur within one month of the first attack
• ~6% more in the following year (Adams & Victor)

5. Risk Stratification - The ABCD² Score

• Score 0: 0% | Score 4: 8% | Score 5: 12% | Score 6: 17% | Score 7: 22%

• 0-3: Low risk (1% stroke in 48h)
• 4-5: Moderate risk (4.1% in 48h)
• ≥6: High risk (8% in 48h)

Note: More recent studies have found the ABCD² score alone is insufficient - it should be combined with DWI-MRI/MRA (ABCD²-I or ABCD³-I scoring) for better prediction. - Rosen's

6. Differential Diagnosis

7. Investigations

Immediate (Emergency) Workup:

1. Non-contrast CT brain - Rule out haemorrhage (hemorrhagic stroke contraindication to antiplatelets)
2. MRI brain with DWI - Detects early infarction (DWI positive = stroke, not TIA); gold standard
3. CT angiography / MR angiography - Carotid and intracranial vessels
4. ECG - Screen for atrial fibrillation
5. Blood glucose - Rule out hypoglycemia
6. CBC, coagulation, lipids, renal function
7. Echocardiogram - Screen for cardiac source (if cardioembolic mechanism suspected)
8. Carotid Doppler - Ipsilateral carotid stenosis assessment

8. Management

A. Antiplatelet Therapy (Cornerstone of Treatment)

"The combination of aspirin and clopidogrel was found to prevent stroke following TIA better than aspirin alone in a large Chinese randomized trial [CHANCE] and the NIH-sponsored POINT trial."

• Harrison's 22E

• DAPT started within 24 hours and continued for 21 days is the current standard
• After 21 days, switch to single antiplatelet (aspirin or clopidogrel alone)
• The benefit of DAPT is confined to the first 21 days (pooled POINT + CHANCE analysis)

"Failure to respond to clopidogrel is linked to carriage of a common CYP2C19 polymorphism...this mutation is common, particularly in Asians."

• Harrison's 22E

B. Anticoagulation

• Indicated when the mechanism is cardioembolism (e.g., atrial fibrillation)
• Direct oral anticoagulants (DOACs) are preferred over warfarin for AF
• Thrombolysis (tPA) is contraindicated if symptoms are improving (a defining feature of TIA)

C. Statin Therapy

• Atorvastatin 80 mg/day (SPARCL trial): significant reduction in secondary stroke and TIA
• Target LDL <70 mg/dL for secondary prevention
• All patients with prior ischemic TIA should receive a statin

D. Blood Pressure Control

• Target <130/80 mmHg (all hypertension should be treated)
• SPRINT trial: SBP <120 mmHg reduced stroke + MI by 43%
• Preferred agents: thiazide diuretics and ACE inhibitors (Harrison's 22E)

9. Carotid Endarterectomy (CEA) - Surgical Prevention

• Symptomatic hemispheric ischemia
• High-grade ipsilateral ICA stenosis
• Institutional perioperative morbidity/mortality ≤6%
• Most beneficial when performed within 2 weeks of symptom onset
• Greater benefit in patients >75 years and in men

10. Secondary Prevention Summary

11. Memory Aids for Internship

• Age ≥60 (1 pt)
• Blood pressure ≥140/90 (1 pt)
• Clinical features: weakness (2 pts), speech only (1 pt)
• Duration: >60 min (2 pts), 10-59 min (1 pt)
• Diabetes (1 pt)

Key References

• Harrison's Principles of Internal Medicine 22E (2025), Chapters 438-439
• Adams & Victor's Principles of Neurology 12E, Chapter 33
• Rosen's Emergency Medicine 10E, Chapter 87
• Frameworks for Internal Medicine, Chapter 43

Yellow Phosphorus Ingestion: Prognosis

Short Answer: BAD - Very Poor Prognosis

Why It's So Dangerous - Mechanism of Toxicity

"Phosphorus is a protoplasmic poison. It affects cellular oxidation. Its effect on cellular metabolism is comparable to ischaemia... This is known as necrobiosis, which is classically manifested in the liver."

• Parikh's Textbook of Medical Jurisprudence, Forensic Medicine and Toxicology

1. Local irritant action on the GI tract
2. Absorbed phosphorus stays in blood in elemental form for 1-2 days
3. Gets oxidised to hypophosphorous and phosphorous acids - acting as a hepatotoxic, protoplasmic poison
4. Causes widespread fatty infiltration and degeneration, especially in liver and cerebral cortex
5. Disturbs carbohydrate, fat, and protein metabolism - fat deposits in liver at the cost of glycogen (necrobiosis)
6. Leads to acute yellow atrophy of the liver - the pathognomonic end-stage finding

Fatal Dose and Fatal Period

The Triphasic Clinical Course (Key Feature for Exams)

Stage 1 - GI Irritation (within 2-6 hours, lasts 1-2 days)

• Garlic taste in mouth, garlic odour in breath
• Luminous vomitus and phosphorescent faeces (glows in the dark) - pathognomonic
• Burning pain throat to stomach
• Profuse vomiting (bile-stained, blood-tinged)
• Diarrhoea, intense thirst
• Cardiac and respiratory depression, cold clammy skin
• Patient may die at this stage from cardiovascular collapse

Stage 2 - Apparent Recovery / "Honeymoon Phase" (2-4 days)

• Symptoms reduce in intensity, vitals seem to improve
• Patient and doctor may feel reassured
• This is deceptive - phosphorus is being absorbed and oxidised, silently damaging the liver

Stage 3 - Hepatorenal Failure (starts around Day 4-7)

• Vomiting and diarrhoea return more severely
• Jaundice sets in and deepens rapidly
• Liver enlarged, soft, tender → later shrinks (acute yellow atrophy = necrosis)
• Haemorrhagic manifestations: epistaxis, haematemesis, haematuria, melaena, petechiae - from coagulopathy (hypoprothrobinaemia)
• Renal failure: oliguria → anuria; urine contains blood, albumin, bile, amino acids (leucine, tyrosine, cysteine)
• CNS: headache, tinnitus, vertigo, insomnia, delirium, priapism (frequent), cramps, paralysis
• Hypoglycaemia, weak irregular pulse, falling BP, pulmonary oedema, cyanosis
• Death from hepatic and renal insufficiency

"The clinical picture is suggestive of acute yellow atrophy of the liver."

• Parikh's Textbook

Prognostic Markers (Recent Evidence)

• Overall mortality: 36.5%
• Mean survival among those who died: 5.26 days after ingestion
• Symptoms (GI + neurological) typically appear ~48 hours post ingestion

"As progression to death occurs within a week of yellow phosphorus ingestion in most cases, determining prognosis as early as possible enables swift referral to a liver transplant centre."

• Ramkumar et al., Clin Toxicol 2024 [PMID: 39132751]

Treatment (and Why Prognosis Remains Poor Despite Treatment)

Summary Table