DEFINITIONS

1. Convulsions

• Tonic = sustained muscle contraction (rigidity)
• Clonic = rhythmic, alternating contraction and relaxation (jerking)
• Tonic-clonic = the classic "grand mal" - starts with rigidity, then jerking, followed by post-ictal confusion

2. Aural Hematoma

• Cause: Most often seen in wrestlers, boxers, and rugby players ("wrestler's ear")
• Risk: If untreated or if it re-accumulates, it leads to avascular necrosis of cartilage and fibrocartilaginous organization, producing the classic deformity called "cauliflower ear"
• Management: Prompt drainage by aspiration or incision, followed by a compression dressing or splint to prevent re-accumulation

3. Mural Thrombosis

• Cardiac mural thrombus: Forms on the endocardium of a non-contractile, akinetic wall segment - classically after myocardial infarction (especially left ventricular anterior wall MI). Damaged endothelium + sluggish flow (Virchow's triad) predisposes to clot formation.
• Arterial mural thrombus: Occurs in aneurysms (e.g., abdominal aortic aneurysm) or over atherosclerotic plaques where endothelium is disrupted.
• Danger: Fragments can break off and embolize - cardiac mural thrombi cause systemic arterial emboli (e.g., stroke, limb ischemia); ventricular mural thrombus is a complication in up to 20% of anterior MI.
• Anticoagulation (e.g., warfarin) is used to reduce embolism risk.

4. Ascoli Test (Ascoli's Thermoprecipitin Test)

• A heat extract is made from the suspected infected tissue, hide, wool, or soil
• The extract is layered over Ascoli's serum (antiserum against B. anthracis)
• A white ring/precipitate forming at the interface = positive result, indicating the presence of B. anthracis thermostable somatic antigen (polysaccharide)

• Useful for diagnosing anthrax in dead animals or old specimens where the organism is no longer viable and culture is impossible
• Used in veterinary and public health investigations of anthrax outbreaks
• Named after Maurizio Ascoli, who developed it in 1911

5. Osteomalacia

• In children, the same defect affects growing cartilage and bone, producing rickets
• In adults, the growth plates are closed, so only the bone matrix is affected = osteomalacia

• Vitamin D deficiency (most common) - inadequate sunlight, dietary deficiency, malabsorption
• Renal phosphate wasting (X-linked hypophosphatemia, Fanconi syndrome)
• Chronic renal failure (impaired 1-hydroxylation of vitamin D)
• Drugs: anticonvulsants (phenytoin), bisphosphonates

• Bone pain and tenderness, proximal muscle weakness
• Pathological fractures; Looser's zones (pseudofractures) on X-ray
• Low serum calcium, phosphate; raised ALP; low 25(OH)D

LONG QUESTIONS

1. TETANUS

Definition

Etiology

• Causative organism: Clostridium tetani - an anaerobic, gram-positive, spore-forming rod
• Spores are highly resilient and resist boiling and many disinfectants
• Spores survive in soil, dust, and in the intestinal tracts of many animals
• Entry: through wounds, abrasions, open fractures, injection sites, or the umbilical stump in neonates
• ~20-30% of cases have no identifiable wound

Pathogenesis

1. Spores enter a wound and germinate in an anaerobic environment
2. C. tetani produces tetanospasmin (tetanus toxin) - one of the most potent biological toxins known
3. Toxin undergoes retrograde axonal transport up motor neurons to the spinal cord and brainstem
4. Toxin crosses synapse to GABAergic and glycinergic inhibitory interneurons
5. Its light chain (zinc-dependent endopeptidase) cleaves VAMP2 (synaptobrevin) - blocking inhibitory neurotransmitter release
6. Result: unregulated, continuous motor neuron firing → rigid spasms
7. Autonomic involvement (circulating catecholamines) → cardiovascular instability in severe disease

Clinical Features

Types:

Progression:

• Trismus ("lockjaw") is the most common early symptom
• Neck and body rigidity, dysphagia, pharyngeal/laryngeal spasms
• Risus sardonicus (fixed sardonic grin from facial muscle spasm)
• Opisthotonos (arched back from paraspinal spasm)
• Autonomic disturbance in the 2nd week: tachycardia/bradycardia, hypertension/hypotension, sweating, hypersalivation
• Cause of death: laryngospasm causing respiratory failure, or cardiovascular events from autonomic instability

Ablett Classification of Severity:

Diagnosis

• Clinical diagnosis - no reliable laboratory confirmation
• Culture of C. tetani from wound cannot confirm tetanus
• Serum anti-tetanus IgG >0.1 IU/mL suggests protection (argues against tetanus)
• Spatula test: touching the posterior pharyngeal wall with a spatula - in tetanus, the patient bites (involuntary jaw closure) rather than gagging

Treatment

1. Wound Care

• Clean and debride the wound to remove anaerobic foci
• Perform wound care after antitoxin administration

2. Antibiotic

• Metronidazole 400 mg rectally or 500 mg IV every 6 hours for 7 days (preferred)
• Alternative: Penicillin 100,000-200,000 IU/kg/day (though theoretically may worsen spasms by binding GABA receptors)

3. Antitoxin (neutralize unbound toxin)

• Human tetanus immunoglobulin (HTIG): 500-5000 IU IM (single dose) - preferred; fewer anaphylaxis reactions
• Equine antitoxin: 10,000-20,000 IU IM after hypersensitivity testing (used in resource-poor settings)

4. Control of Spasms

• Benzodiazepines (diazepam, midazolam) - first-line for muscle relaxation and sedation
• Propofol infusion for refractory cases
• Neuromuscular blocking agents + mechanical ventilation for severe Grade III-IV

5. Autonomic Disturbance

• Magnesium sulfate IV infusion - reduces spasms and autonomic instability
• Beta-blockers (labetalol, esmolol) for tachycardia/hypertension
• Avoid morphine (can worsen autonomic instability)

6. Supportive Care

• Mechanical ventilation (tracheostomy often required)
• Quiet, dark room - avoid stimulation which precipitates spasms
• NG tube feeding
• DVT prophylaxis

7. Active Immunization

• Tetanus does not confer immunity; vaccinate after recovery

Prevention

• Primary immunization: DTP/DPT vaccine series in childhood
• Booster: Td toxoid every 10 years
• Post-exposure prophylaxis: Based on wound type and vaccination history:
  • Unimmunized + tetanus-prone wound: HTIG + tetanus toxoid
  • Immunized but >10 years since last booster: toxoid alone

2. BRUCELLOSIS

Definition

Etiology

Epidemiology & Transmission

• Worldwide distribution; endemic in Mediterranean, Middle East, Central Asia, Latin America, sub-Saharan Africa
• Routes of infection:
  1. Ingestion: unpasteurized dairy products (milk, cheese), undercooked meat - most common in civilians
  2. Inhalation: aerosolized particles in abattoirs, farms, veterinary labs - occupational
  3. Direct contact: contaminated wounds or mucous membranes (veterinarians, slaughterhouse workers)
  4. Inoculation: accidental injection of live attenuated vaccine (veterinarians)
  5. Human-to-human transmission is rare (sexual contact, breast milk, blood transfusion)
• Brucella is a potential bioterrorism agent

Pathogenesis

• Brucella is a facultative intracellular pathogen - survives and replicates inside macrophages and monocytes
• Evades killing by preventing phagosome-lysosome fusion
• Disseminates via lymphatics and bloodstream to reticuloendothelial system (liver, spleen, bone marrow, lymph nodes)
• Granuloma formation (characteristic histopathology)
• Immune response is primarily cell-mediated (Th1)

Clinical Classification

Clinical Features

General (>90% of patients):

• Undulant fever (classic: rises in afternoon/evening, falls by morning with drenching sweats)
• Malaise, chills, sweats, fatigue, weakness, headache, anorexia
• Myalgias and weight loss (>50%)

Signs:

• Fever (>39.4°C in 95%), splenomegaly (10-15%), hepatomegaly, lymphadenopathy (14%)
• Relative bradycardia (pulse-temperature deficit) - characteristic

Osteoarticular Complications (most common localized form):

• Sacroiliitis - most common (unilateral, strongly suggests brucellosis in endemic areas)
• Spondylitis/spondylodiscitis - especially lumbar; paravertebral abscess
• Peripheral arthritis, bursitis, osteomyelitis

Other Organ Involvement:

• Neurobrucellosis: meningitis, encephalitis, myelitis (rare but serious)
• Endocarditis: rare but most common cause of death in brucellosis
• Genitourinary: orchitis/epididymitis in males; spontaneous abortion in pregnant women
• Hepatic: hepatitis, hepatic granulomas
• Pulmonary: pneumonia, pleural effusion (uncommon)

Diagnosis

1. Culture (gold standard):
   • Blood culture: positive in 10-30% of acute cases (up to 90% with longer incubation)
   • Bone marrow culture: higher yield than blood
   • Inform laboratory (biohazard risk)
2. Serology:
   • Standard tube agglutination test (STAT/SAT): most widely used; titer ≥1:160 is significant
   • Rose Bengal card test: rapid screening test
   • 2-mercaptoethanol (2-ME) agglutination: distinguishes IgM (acute) from IgG (chronic)
   • ELISA: sensitive, detects IgM and IgG
   • A 4-fold rise in titer in paired sera confirms diagnosis
3. Nucleic acid amplification (PCR): rapid and highly accurate; cannot confirm cure
4. Lab findings: mild anemia, neutropenia or lymphocytosis, elevated liver enzymes

Treatment (Goldman-Cecil Medicine)

• Doxycycline 200 mg/day orally for 6 weeks + Streptomycin 1 g IM/day for 2-3 weeks OR
• Doxycycline 200 mg/day for 6 weeks + Gentamicin 3-5 mg/kg/day for 1-2 weeks

• Doxycycline + Rifampicin 15-20 mg/kg/day for 6 weeks (more convenient, but higher relapse rate)
• Ofloxacin + Rifampicin for 6 weeks

• Children <8 years / Pregnant: TMP-SMX + Rifampicin for 6 weeks (doxycycline contraindicated)
• Neurobrucellosis: Doxycycline + Rifampicin + TMP-SMX for ≥6 weeks; add ceftriaxone
• Endocarditis: bactericidal drugs + surgical valve replacement (high mortality with medical therapy alone)
• Spondylitis: treat for up to 3 months

Prevention

• Pasteurization of milk and dairy products
• Proper cooking of meat
• Protective clothing and equipment for occupational exposure
• Veterinary vaccination of livestock (live attenuated vaccines: RB51 for cattle, Rev-1 for sheep/goats)
• No human vaccine currently available
• Bioterrorism threat requires heightened lab surveillance

3. EPILEPSY

Definition

• Two or more unprovoked seizures, OR
• One unprovoked seizure in the setting of an underlying condition carrying a high risk of recurrence (e.g., structural brain abnormality, EEG showing epileptiform activity)

Etiology / Classification of Causes (ILAE 2017)

Classification of Seizures (ILAE 2017)

A. Focal Onset Seizures (originate in one hemisphere)

• Motor: hand jerking, Todd's paralysis post-ictally
• Sensory: tingling, visual/auditory/olfactory hallucinations
• Autonomic: tachycardia, flushing
• Psychic: déjà vu, fear, epigastric aura

• Blank staring, oroalimentary automatisms (lip smacking, chewing)
• Gestural automatisms, post-ictal confusion
• Duration: 30-120 seconds

B. Generalized Onset Seizures (both hemispheres from onset)

C. Unknown Onset Seizures

Pathophysiology

• Seizures arise from imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission
• Focal seizures: abnormal synchronized discharge in a limited cortical network
• Generalized seizures: rapid bilateral cortical engagement via thalamocortical circuits
• Spreading depolarization waves underlie seizure propagation

Diagnosis

1. Clinical History

• Description of events (eye-witness account), duration, frequency, post-ictal period
• Precipitating factors, family history, developmental history

2. EEG (Electroencephalogram) - Key diagnostic tool

• Interictal EEG: may show epileptiform discharges (spikes, sharp waves) even between seizures
• Focal spikes/slow waves: focal epilepsy
• Generalized 3 Hz spike-wave: typical absence epilepsy
• Video-EEG monitoring for refractory/unclear cases

3. Neuroimaging

• MRI brain (with thin coronal cuts through hippocampus): preferred over CT
• Detects: hippocampal sclerosis, cortical dysplasia, tumors, vascular malformations
• CT used acutely to exclude hemorrhage

4. Blood Tests

• Glucose, electrolytes (Na, Ca, Mg), renal/liver function, CBC
• Genetic testing when applicable

5. Autoimmune Panel

• Anti-NMDAR, anti-LGI1, anti-CASPR2 antibodies (in suspected autoimmune epilepsy)

Treatment

A. Anti-Seizure Medications (ASMs)

B. Status Epilepticus (Emergency)

• Benzodiazepines first: Lorazepam IV (or diazepam IV, midazolam IM/buccal)
• Second line: Phenytoin/Fosphenytoin IV, Valproate IV, Levetiracetam IV
• Refractory: Propofol, Midazolam, or Thiopental infusion under EEG monitoring in ICU

C. Surgical Treatment (for medically refractory epilepsy - ~30% of patients)

• Temporal lobectomy - best results: ~70% seizure-free in mesial temporal lobe epilepsy with hippocampal sclerosis
• Lesionectomy (resection of tumor, dysplasia, vascular malformation)
• Corpus callosotomy (for atonic/drop attacks)
• Hemispherotomy (for hemispheric epilepsy in children)

D. Neurostimulation

• Vagus Nerve Stimulation (VNS): chronic stimulation reduces seizure frequency by ~50%
• Responsive Neurostimulation (RNS): detects and aborts seizure onset
• Deep Brain Stimulation (DBS): targets bilateral anterior thalamic nuclei

E. Ketogenic Diet

• High-fat, low-carbohydrate diet; especially effective in children, Dravet syndrome, glucose transporter deficiency
• Mechanism: ketone bodies alter neuronal metabolism and raise seizure threshold

Special Considerations

• Women of childbearing age: valproate teratogenicity (neural tube defects); prefer lamotrigine or levetiracetam in pregnancy
• Driving restrictions: most jurisdictions require a seizure-free period (typically 6-12 months) before driving
• Mortality: SUDEP (Sudden Unexpected Death in Epilepsy) - 1 per 1000 patient-years; higher with uncontrolled generalized tonic-clonic seizures