CT Scan (Computed Tomography)

Definition

Principle

• A source of X-ray photons rotates around the patient; detectors on the opposite side measure the attenuation (absorption) of the beam as it passes through tissues.
• The passage of photons is impeded in proportion to tissue density - denser structures absorb more X-rays.
• Attenuation is measured in Hounsfield Units (HU), calibrated to a standard scale:

• A single CT image is divided into tiny blocks called pixels (or voxels in 3D). Each pixel's gray shade reflects the HU of that point.
• Normal splenic parenchyma, for example, shows uniform attenuation of 40-60 HU on non-contrast CT.

Image Display: Windows

• Window width: the range of HU values displayed.
• Window level: the center of that range.

• Lung window: optimized for low-density lung parenchyma (high-density structures appear white).
• Mediastinal/soft tissue window: optimized for soft tissue (low-density lung appears black).
• Bone window: for cortical and trabecular bone detail.

Types of CT Scans

Contrast Agents

• Intravenous (IV) contrast: Iodinated agents (e.g., iohexol). Used to enhance blood vessels, tumors, inflammation.
• Oral contrast: Differentiates bowel from lymph nodes, scar, or tumor - common in abdominal CT.
• Contrast enhancement pattern: An increase in attenuation of >10 HU after IV contrast suggests a solid mass; enhancement >20 HU indicates malignancy (in renal lesions).

• Renal impairment / contrast nephropathy risk (especially diabetics with renal insufficiency)
• Allergy to iodinated contrast
• Pregnancy (relative contraindication)

Clinical Applications

Advantages over Other Modalities

• Faster acquisition than MRI (especially useful in trauma and emergencies)
• Better for bone detail compared to MRI
• No contraindication from metallic implants (unlike MRI)
• Higher sensitivity than plain X-ray for fractures (e.g., growth plate injuries)
• Excellent for calcification, hemorrhage, gas
• Provides 3D reconstructions and multiplanar reformats

Limitations and Risks

• Radiation exposure: Unlike MRI or ultrasound, CT uses ionizing radiation. Roughly 1 fatal cancer is estimated per 1,000 CT scans in pediatric patients - judicious use is especially important in children.
• Contrast nephropathy: Risk in diabetics and patients with renal insufficiency.
• Soft tissue contrast: Inferior to MRI for brain parenchyma, musculoskeletal soft tissues, and spinal cord.
• Artifacts: Beam hardening from metallic implants, patient motion.

Key Points Summary

1. CT = X-rays + computer reconstruction producing cross-sectional images.
2. Attenuation measured in Hounsfield Units; water = 0, air = -1000.
3. Window width/level allows selective visualization of tissues.
4. Contrast (oral/IV) enhances lesion characterization.
5. Gold standard for spinal trauma, head and neck pathology, and acute abdominal emergencies.
6. Radiation risk is a consideration, especially in pediatric and repeated imaging.

PET Scan (Positron Emission Tomography)

Definition

Principle

1. A positron-emitting radiopharmaceutical is injected intravenously (or inhaled).
2. The emitted positron travels a short distance in tissue (<1 mm effective range) before encountering an electron.
3. The positron and electron annihilate, converting their mass to energy - producing two 511-keV photons emitted at exactly 180° from each other.
4. Detectors arranged in a ring around the patient detect these two photons simultaneously (coincidence detection).
5. The simultaneous detection localizes the annihilation event spatially.
6. Computer reconstruction algorithms generate 3D images of tracer distribution.
7. Attenuation correction (using CT in PET/CT systems) is applied to correct for photon absorption in tissues, improving anatomical detail.

Tracers (Radiotracers/Radiopharmaceuticals)

• ¹⁸F has a relatively long half-life (110 min), allowing commercial shipping without an on-site cyclotron.
• Shorter-lived isotopes (¹¹C, ¹⁵O) require an on-site cyclotron, limiting their use to research centers.

FDG Mechanism

1. FDG (a glucose analog) is taken up by cells via glucose transporters.
2. It is phosphorylated by hexokinase to FDG-6-phosphate.
3. FDG-6-phosphate cannot be further metabolized and is irreversibly trapped in the cell.
4. Metabolically active cells (tumors, neurons) accumulate FDG progressively, creating high contrast between target and normal tissue.
5. Importantly, increased FDG uptake is not unique to malignancy - it also occurs in inflammation, infection, and benign tumors.

Standard FDG-PET Protocol

• Fasting: 6-12 hours before injection (minimizes competing glucose).
• FDG dose: ~10 mCi (370 MBq) IV.
• Uptake period: 30-60 minutes post-injection (allows sufficient tissue accumulation).
• Scanning time: 30-60 minutes, supine position, whole-body at multiple table positions.
• Hydration: Patients encouraged to drink water to minimize urinary collection.
• Muscle relaxation: Benzodiazepines used in some centers to prevent normal muscle uptake mimicking tumor.

Quantification - Standardized Uptake Value (SUV)

• SUV is the most commonly used semi-quantitative method.
• Measured at a single time point after tracer injection.
• Formula: Activity concentration in tissue (Bq/mL) / [Injected dose (Bq) / Body weight (g)]
• Higher SUV = more metabolic activity.
• Helps differentiate malignant from benign uptake and monitors treatment response.
• Limitation: only comparable at the same post-injection time point.

PET/CT and PET/MRI (Hybrid Systems)

Clinical Applications

1. Oncology (Primary Use)

• Detection, staging, treatment response, and recurrence of cancers.
• Particularly useful in: lymphoma, lung cancer, colorectal cancer, melanoma, head and neck cancers, esophageal cancer.
• PET/CT for co-registration of metabolic and anatomical data improves staging accuracy.
• FDG uptake reflects viable tumor cells (though not directly correlated with proliferative rate).
• ⁶⁸Ga-DOTATATE PET for neuroendocrine tumors.

2. Neurology

• Alzheimer's disease: FDG-PET shows hypometabolism in parietal/temporal cortex; amyloid PET detects amyloid-beta plaques; tau PET for tau tangles.
• Epilepsy: Ictal/interictal CBF SPECT and FDG-PET for seizure focus localization.
• Brain tumors: FDG-PET for grading and differentiating tumor recurrence from radiation necrosis.
• Parkinson's disease: ¹⁸F-FDOPA for dopamine synthesis; DAT-SPECT also used.
• Dementia differentiation: Severity of vascular dementia relates to volume of metabolically impaired tissue.

3. Cardiology

• Myocardial viability assessment (hibernating vs. infarcted myocardium).
• Blood flow and ischemia evaluation.

4. Infection/Inflammation

• FDG-PET detects metabolically active inflammatory lesions; used in fever of unknown origin, vasculitis.

Advantages

• High sensitivity - detects molecular/metabolic changes before structural changes appear on CT/MRI.
• Whole-body imaging in a single session.
• Wide range of tracers for diverse physiological targets.
• Quantitative (SUV) and qualitative assessment both possible.
• PET/CT provides simultaneous functional + anatomical information.
• Picomolar sensitivity - detects targets at extremely low concentrations.

Disadvantages / Limitations

PET vs. SPECT - Key Differences

Key Points Summary

1. PET detects positron annihilation photons from radiotracers to map metabolic activity.
2. ¹⁸F-FDG is the most widely used tracer - exploits enhanced glucose metabolism of tumors.
3. FDG is irreversibly trapped in metabolically active cells via hexokinase phosphorylation.
4. SUV is the standard semi-quantitative measure of tracer uptake.
5. PET alone has poor anatomical resolution - PET/CT hybrid systems overcome this limitation.
6. Major clinical uses: oncology staging/response, Alzheimer's, epilepsy, brain tumors.
7. Limitations include radiation dose, poor spatial resolution, non-specificity of FDG, and high cost.

Biopsy and Its Classification

Definition

Indications

• Suspected malignancy (primary diagnosis)
• Characterization of known tumor (grade, histological type)
• Assessment of treatment response
• Diagnosis of inflammatory, infectious, or granulomatous conditions
• Intraoperative confirmation before proceeding to definitive resection (frozen section)
• Determination of surgical margins after excision

Classification of Biopsy

A. By Technique

1. Fine Needle Aspiration Cytology (FNAC)

• Uses a thin needle (22-25 G) with or without a syringe to aspirate cells (not tissue cores) from a mass.
• Yields a cytological smear - individual cells, not tissue architecture.
• Advantages: Simple, fast, cost-effective, fewer complications, good for obese patients or lesions near neurovascular structures, can be done in an outpatient setting.
• Disadvantages: Small sample; cannot assess tissue architecture; cannot distinguish invasive from non-invasive tumor (e.g., invasive vs. in-situ carcinoma of breast); requires an expert cytopathologist.
• Uses: Thyroid nodules, lymph nodes, breast lumps, salivary gland swellings, superficial masses.

2. Core Needle Biopsy (CNB / Tru-cut Biopsy)

• Uses a wider needle (14-18 G) with a spring-loaded device to obtain a small core of tissue.
• Provides histological information - tissue architecture is preserved.
• Can be performed by direct palpation or image-guided (ultrasound, CT, stereotactic).
• Advantages: More tissue than FNAC; cost-effective; can differentiate invasive from in-situ lesions; can be done as outpatient procedure.
• Disadvantages: More complications than FNAC (bleeding, hematoma, infection); sampling error exists - 19-44% of atypical ductal hyperplasia on CNB found to have carcinoma on full excision.
• Note: There have been reports of tumor seeding along the needle tract with core biopsy in some tumors (e.g., parotid), making it controversial in certain sites.

3. Incisional Biopsy

• Surgical removal of a portion of the lesion/mass for diagnosis.
• Provides an adequate tissue sample - considered the gold standard for histological diagnosis.
• Indications: Large lesions (>3 cm) where excisional biopsy is not feasible; when needle biopsy is non-diagnostic or cannot be performed.
• Advantages: Adequate tissue for full histological, immunohistochemical, molecular, and flow cytometric analysis.
• Disadvantages: Operative procedure with more complications (bleeding, infection, hematoma); may compromise definitive resection if not correctly planned.
• Important surgical principles:
  • Incision should be oriented to allow excision of the biopsy scar at definitive surgery.
  • Should directly overlie the lesion (no tunneling from a distant site - avoids contaminating a wider field).
  • Meticulous hemostasis - hematoma contaminates tissue planes and complicates follow-up.
  • Surgeon should mark margins with sutures/clips; pathologist should ink the margins.
• Special case - Lymphoma: An entire lymph node must be removed by open incisional biopsy to preserve lymph node architecture and provide sufficient tissue for molecular and flow cytometric analysis. FNAC alone is not acceptable for lymphoma diagnosis.

4. Excisional Biopsy

• Complete removal of the entire lesion with a margin of normal tissue - both diagnostic and potentially therapeutic.
• Performed with curative intent - adequate tissue excised around the lesion to ensure negative surgical margins.
• Indications: Small lesions (<3 cm) unlikely to be malignant; skin lesions; polyps (should be completely excised rather than partially biopsied to allow assessment of invasion through muscularis mucosae); lesions in expendable bones (e.g., proximal fibula, distal ulna).
• Advantages: Removes entire lesion; definitive for small benign lesions; provides complete tissue for assessment.
• Disadvantages: More complications; if margins are positive, re-excision is needed; not appropriate for large or deep-seated malignant lesions as primary procedure (risk of inadequate margins).
• Note: If a polyp is partially biopsied, the pathologist may lack sufficient material to assess invasion through the muscularis mucosae (the criterion of malignancy), and the lesion may be hard to find again. Therefore, polyps should always be completely excised.

5. Punch Biopsy

• A circular cutting instrument (punch/Keyes punch) of 2-8 mm diameter is pressed into the skin with a rotating motion, removing a cylindrical core of skin including epidermis, dermis, and superficial subcutis.
• Mainly used in dermatology for skin lesions.
• Provides full-thickness skin sample.
• Suitable for inflammatory dermatoses, blistering disorders, pigmented lesions.

6. Shave Biopsy

• A blade or scissors is used to shave off a superficial lesion flush with or just below the skin surface.
• Provides superficial tissue only (epidermis ± papillary dermis).
• Uses: Exophytic or pedunculated skin lesions; seborrheic keratoses; suspected basal cell carcinoma.
• Limitation: Traditionally discouraged for melanoma as it may confound accurate assessment of Breslow thickness (tumor depth), though it remains the most common technique by which melanomas are biopsied in practice.

7. Curettage Biopsy

• A dermal curette is used to scrape the lesion.
• Used for superficial skin lesions and certain basal cell carcinomas.

8. Endoscopic Biopsy

• Tissue obtained under direct endoscopic vision using forceps passed through the biopsy channel of a scope (colonoscope, bronchoscope, cystoscope, gastroscope).
• Technique: Closed forceps directed at lesion, opened, pushed into tissue, closed and withdrawn - causing "tenting" of mucosa.
• Biopsy of gastric ulcers: All four quadrants at the edges should be sampled (not the center - insufficient tissue for assessing invasion).
• Contraindicated: In patients on anticoagulants or with clotting disorders.
• Post-biopsy: Barium enema should not be done within 10 days of biopsy (risk of perforation).

B. By Approach / Guidance

C. By Timing (Processing Method)

1. Frozen Section (Intraoperative / Rapid Section)

• Tissue obtained during surgery is immediately frozen (using liquid CO₂ or isopentane at -50°C), cut into thin sections (5-10 μm) in a cryostat, stained (H&E, methylene blue, PAS), and examined within ~10 minutes.
• Results communicated directly to the surgeon in the operating room.
• Indications:
  • No preoperative diagnosis available
  • Unexpected intraoperative findings need identification
  • Confirming adequacy of surgical margins
  • Guiding extent of resection (proceed vs. stop)
  • Confirming diagnosis before definitive resection (must match clinical and radiological findings - if discrepancy, definitive surgery deferred)
• Limitation: Lower quality than permanent sections; artifact from freezing.

2. Permanent (Paraffin) Section

• Standard processing: fixation in formalin, paraffin embedding, microtome sectioning, H&E staining.
• Provides superior morphological detail compared to frozen sections.
• Takes 24-72 hours.
• Gold standard for final histological diagnosis.

Summary Comparison Table

Complications of Biopsy

• Bleeding / hematoma - most common; hematoma contaminates tissue planes
• Infection
• Tumor seeding along biopsy tract (especially core needle biopsy of parotid, retroperitoneum)
• Pathologic fracture (during bone biopsy - biopsy hole should be round to minimize stress concentration)
• Compromise of definitive resection if biopsy is poorly planned

General Principles of Good Biopsy Practice

1. Take biopsy from the edge (not the center/necrotic core) of a lesion.
2. Incision should be oriented along the limb axis (orthopaedic tumors) to allow excision of the biopsy tract at definitive surgery.
3. The biopsy incision should directly overlie the tumor - no tunneling.
4. Meticulous hemostasis to prevent hematoma.
5. Biopsy result must be consistent with clinical and radiological findings - if discrepant, repeat or proceed to open biopsy.
6. Polyps: always excise completely.
7. For lymphoma: always perform excisional/incisional open biopsy of a whole node - FNAC is insufficient.
8. Biopsy every infection; culture every tumor - always send cultures at biopsy to rule out infection mimicking tumor.

Trigeminal Neuralgia

Definition

Epidemiology

• Incidence: ~4 per 100,000 individuals.
• Onset: >90% of patients are over 40 years of age; incidence progressively increases with age.
• Sex: Slightly more common in women (ratio ~1.5:1).
• Rare familial cases exist, suggesting a genetic component in some families.
• In younger patients, consider multiple sclerosis (MS) as an underlying cause.

Classification (ICHD-3)

Anatomy of the Trigeminal Nerve (CN V)

• V1 (Ophthalmic) - forehead, scalp, upper eyelid, cornea
• V2 (Maxillary) - cheek, upper lip, upper teeth, nose
• V3 (Mandibular) - lower lip, chin, lower teeth, jaw

• V2 and V3 combined: most common
• V2 alone (cheek, upper teeth): common
• V3 alone (chin, lower teeth, jaw): common
• V1 alone (ophthalmic, around eye): extremely rare
• Bilateral TN: very rare; if present, suspect MS

Pathogenesis

• Classical TN: Neurovascular compression of the trigeminal nerve root entry zone (REZ) at the pons - most commonly by the superior cerebellar artery, less often by the anterior/posterior inferior cerebellar arteries or superior petrosal vein.
• Vascular compression increases with age (vessel ectasia/elongation).
• This causes focal demyelination of primary trigeminal afferents near the nerve root entry zone.
• Demyelination leads to focal hyperexcitability → ectopic and repetitive neuronal discharges → paroxysmal pain (the "ignition hypothesis").
• Pathological studies: vacuolated neurons, segmental demyelination, vascular changes in the gasserian ganglion.
• Secondary TN: Structural lesions (MS plaques, tumors) cause similar focal demyelination/compression.

Clinical Features

Pain Characteristics

• Quality: Electric shock-like, lancinating (shooting), stabbing, or burning.
• Onset/Offset: Abrupt onset and termination - each attack lasts seconds (usually <2 minutes).
• Frequency: Attacks may be repetitive at short intervals, blurring into one another; may occur many times daily during exacerbations.
• Laterality: Strictly unilateral (bilateral is very rare).
• Location: Distribution of V2 and/or V3 most commonly (cheek, chin, lower/upper teeth); V1 rarely.
• Refractory period: After a volley of pain, there is a brief period during which pain cannot be triggered.
• Interictal pain: Most patients are pain-free between attacks; some have a dull, continuous background pain (especially secondary TN).
• Sleep: Attacks during sleep are uncommon but do occur.

Trigger Factors

• Touching the face / nasolabial fold (commonest trigger zone - may be remote from pain site)
• Chewing / mastication
• Teeth brushing
• Talking / swallowing
• Cool breeze striking the face
• Shaving

Consequences

• Patients avoid triggers - refuse to eat, talk, brush teeth.
• Weight loss, dehydration, depression with frequent attacks.
• Prompt treatment is essential.

Physical Examination

• Classical TN: Neurological examination is normal - no sensory deficit, motor division intact.
• Presence of sensory loss or masticatory muscle weakness suggests a secondary cause (trigeminal neuropathy rather than neuralgia) - indicates a lesion at the gasserian ganglion, main sensory root, or root entry zone in the pons.
• A careful history and examination help distinguish classical from secondary TN.

Diagnostic Criteria (ICHD-3 Summary)

1. Paroxysmal attacks of pain lasting from a fraction of a second to 2 minutes.
2. Affecting one or more divisions of the trigeminal nerve.
3. Pain is intense, sharp, stabbing, electric shock-like.
4. Precipitated by innocuous stimuli to the face.
5. Each attack is stereotyped in the same patient.
6. No neurological deficit (in classical TN).

Investigations

• Idiopathic TN: no laboratory or radiographic abnormalities.

Differential Diagnosis

Treatment

A. Medical (First-line)

1. Sodium Channel Blockers (First-Line - Drugs of Choice)

• Side effects of carbamazepine (especially if introduced quickly): vertigo, drowsiness, ataxia - particularly in elderly.
• Start at lowest effective dose; taper slowly to check for remission once pain is controlled.

2. Second-Line Agents

B. Surgical Treatment

1. Peripheral Nerve Block / Alcohol Block

• Injection of absolute alcohol into peripheral branches (infraorbital, mental/mandibular, supraorbital nerves).
• 0.5-0.75 mL of absolute alcohol for mandibular division.
• Pain relief in high proportion; but relapse at 6-18 months is common.
• Can be repeated 1-2 times; beyond that, more proximal/lasting procedures preferred.
• Advantages: Low morbidity, temporary sensory loss, preserves corneal sensation.

2. Percutaneous Procedures (Ganglion/Gasserian Ganglion Level)

• Best for elderly patients or those with medical comorbidities (least invasive).

3. Stereotactic Radiosurgery (Gamma Knife)

• Focused radiation to the trigeminal nerve root.
• Non-invasive (no incision).
• Effective, but relatively high recurrence rate.
• Patients with prior surgery have increased risk of facial dysesthesia post-Gamma Knife.

4. Microvascular Decompression (MVD) - Jannetta Procedure

• The definitive surgical treatment - directly addresses the presumed mechanism.
• Best for: young, healthy patients refractory to medical therapy with classical TN.
• Procedure: Posterior fossa craniotomy (retromastoid craniectomy) → exploration of trigeminal nerve root entry zone → identification of offending vessel → dissection away from nerve → placement of synthetic padding (Teflon) to prevent future compression.
• Results: Jannetta's series of 1155 patients - 70% had excellent pain relief at 10 years.
• Major advantage: Relieves pain without producing anesthesia - preserves facial sensation; longest duration of pain relief.
• Disadvantages: Requires posterior fossa exploration; mortality rate ~1%; risk of injury to CN IV, VII, VIII.
• If no vascular loop is found at surgery: options include partial/complete sensory root section or subsequent radiofrequency procedure.

Summary: Choosing Surgical Approach

Course and Prognosis

• TN has an exacerbating and remitting course over many years.
• Exacerbations: painful attacks many times daily for weeks/months.
• Spontaneous remissions occur and can last months to years; remissions tend to become shorter with time.
• Medications can be tapered during remissions to check if spontaneous remission has occurred.
• MVD is often curative.
• Patients with pain triggered by mastication are at risk of weight loss and inanition - prompt treatment is essential.

Key Points Summary

1. TN = unilateral, paroxysmal, electric shock-like facial pain in CN V distribution, triggered by light touch.
2. V2 + V3 combined is the most common distribution; V1 alone is extremely rare.
3. Normal neurological exam in classical TN - any sensory deficit suggests secondary cause.
4. MRI brain is mandatory to exclude secondary causes (MS, tumor, vascular loop).
5. Carbamazepine is first-line drug (sodium channel blocker); start low, titrate slowly.
6. Monitor CBC, LFTs, serum Na during carbamazepine therapy.
7. MVD is definitive surgery for young, fit patients - directly addresses neurovascular compression.
8. For elderly/unfit patients - percutaneous radiofrequency thermocoagulation is procedure of choice.
9. Bilateral TN should always raise suspicion for multiple sclerosis.