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Epilepsy - Management & Treatment Guidelines (Exam Notes)

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1. When to Start Antiseizure Drug (ASD) Therapy

Risk of recurrence after first unprovoked seizure: 31-71% in first 12 months.

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2. General Principles of ASD Selection

• Monotherapy first - controls seizures with minimum toxicity in most patients
• Choice depends on: seizure type > expected side effects > drug interactions > comorbidities > cost > dosing frequency
• Target: complete seizure freedom with no side effects
• ~30% of focal epilepsy patients are refractory to medical treatment

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3. Drug Selection by Seizure Type

Exam trap: CBZ/PHT given for IGE (absence, myoclonic) can worsen seizures.

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4. Key Antiseizure Drugs - Quick Reference

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5. Therapeutic Drug Monitoring (TDM)

• Change in formulation
• Breakthrough seizures
• Adding/removing interacting drug
• Pregnancy
• Assessment of adherence

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6. Refractory Epilepsy

• Defined as failure of 2 adequate trials of appropriate ASDs
• Affects ~30% of focal epilepsy patients
• Options:
  • Combination pharmacotherapy - combine first-line drugs (CBZ, OXC, LTG, VPA, LEV, PHT)
  • Surgery - resection of epileptogenic focus (requires presurgical evaluation: video-EEG, high-res MRI, neuropsychology, PET/SPECT)
  • Vagus nerve stimulation (VNS)
  • Dietary therapy (ketogenic diet - especially in children)
  • Responsive neurostimulation (RNS)

For drug-refractory focal epilepsy: surgical resection offers excellent chance of seizure-free outcome. Presurgical workup includes EEG, MRI, PET, SPECT (SISCOM - subtraction ictal SPECT coregistered to MRI).

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7. Status Epilepticus (SE) Management

Step-by-Step Protocol (Adams & Victor; Katzung)

• Ensure airway, ventilation, BP; intubate if needed
• IV access; send glucose, electrolytes, toxic screen
• Administer glucose + thiamine (if alcoholism/malnutrition suspected)
• Check for cranial/cervical injury if onset unwitnessed

• IV Lorazepam 0.1 mg/kg (preferred for sustained effect) OR
• IV Diazepam 0.15-0.2 mg/kg
• Prehospital: rectal diazepam, intranasal midazolam, or buccal midazolam
• Lorazepam vs. Diazepam: lorazepam has longer duration (less peripheral redistribution); recent data do not clearly favor one over the other

• IV Levetiracetam, Valproate, Fosphenytoin, or Phenytoin (all equally effective for BZD-refractory SE)
• Seizure cessation in ~50% of patients with any of these agents
• Phenytoin: 15-20 mg/kg IV at 25-50 mg/min in normal saline (precipitates in dextrose!); monitor BP and ECG
• Fosphenytoin: 50-75 mg/min; can be given faster, IM possible
• IV Lacosamide: also used but monitor ECG (arrhythmia risk)

• Anesthetic doses:
  • Midazolam 0.2 mg/kg load then 0.1-0.4 mg/kg/h infusion
  • Propofol 2 mg/kg/h (caution: propofol infusion syndrome >48h)
  • Pentobarbital 10 mg/kg/h
  • Inhalational anesthetics (isoflurane)
• Add phenobarbital 10 mg/min to total 20 mg/kg IV, or carbamazepine/levetiracetam via NG
• Neuromuscular paralysis + continuous EEG monitoring if convulsions persist

• No established therapy - reinstate general anesthesia

Special SE Situations

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8. Epilepsy in Special Populations

Pregnancy

• Valproate has highest teratogenicity - avoid if possible (neural tube defects, cognitive effects in offspring)
• Lamotrigine and levetiracetam are relatively preferred in pregnancy
• AAN/AES 2024 guideline: All ASDs carry some teratogenic risk; decision involves risk-benefit for mother and fetus
• Women with seizure disorders who are seizure-free before conception may be candidates for non-pharmacologic observation

Elderly

• Reduced hepatic metabolism and renal clearance - lower starting doses
• Avoid drugs with complex pharmacokinetics (PHT)

Children

• Infantile spasms (West syndrome): ACTH or vigabatrin
• Childhood absence epilepsy: ethosuximide or valproate
• Juvenile myoclonic epilepsy: valproate (lifelong in most)
• Benign rolandic epilepsy: often spontaneously remits; treatment if frequent

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9. Non-Pharmacologic Management

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10. Precipitating Factors / Lifestyle Advice

• Sleep deprivation - universal precipitant; optimize sleep
• Alcohol intake - lower seizure threshold
• Reflex epilepsy triggers (video games, music, startle)
• Stress reduction (exercise, meditation, counseling)
• Driving - prohibited until cleared by neurologist (per state/local law)
• Avoid swimming alone, working at heights, operating hazardous machinery

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High-Yield Exam Points (Summary)

1. Lorazepam > diazepam for IV SE (longer central nervous system effect due to less peripheral redistribution)
2. Phenytoin IV must be in normal saline (precipitates in dextrose); max rate 50 mg/min (risk: hypotension, heart block)
3. Ethosuximide is only effective for absence - not GTC or focal
4. Valproate = broadest spectrum but highest teratogenicity
5. CBZ/PHT/Vigabatrin/Tiagabine can worsen absence and myoclonic seizures
6. Refractory SE = failure of BZD + 2nd-line agent → anesthesia (pentobarbital, propofol, midazolam)
7. Levetiracetam, Valproate, Fosphenytoin, Phenytoin are equally effective as 2nd-line IV agents in SE
8. Before epilepsy surgery: must do presurgical evaluation (video-EEG, MRI, neuropsychology, ± PET/SPECT)
9. Single unprovoked seizure + normal exam/EEG/imaging = do not treat, defer to outpatient
10. JME = valproate DOC; lifelong therapy usually required; CBZ worsens it

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Ascites - Exam-Focused Notes

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1. Definition & Causes

• Cirrhosis - 84% of all cases (most common)
• Cardiac ascites / heart failure - ~5%
• Peritoneal carcinomatosis - ~10%
• "Mixed" ascites (cirrhosis + 2nd disease)
• Less common: TB peritonitis, pancreatitis, nephrotic syndrome, Budd-Chiari syndrome, massive hepatic metastases, hypothyroidism, Chlamydia infection

First and cheapest confirmation test = abdominal ultrasound (detects as little as 100 mL)

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2. Pathophysiology

In Cirrhosis (Portal Hypertension)

1. Hepatic fibrosis → disrupts sinusoidal architecture → increased hepatic resistance to portal flow
2. Decreased hepatic eNOS → reduced NO → intrahepatic vasoconstriction
3. Paradoxically: splanchnic vasodilation (systemic NO, VEGF, TNF) → pooling of blood → reduced effective circulating volume
4. Kidneys perceive "hypovolemia" → activate RAAS + SNS + ADH → Na and water retention → ascites

In Absence of Cirrhosis

• Peritoneal carcinomatosis / TB - protein-rich fluid from inflamed peritoneum + lymphatic obstruction
• Pancreatic ascites - leakage of pancreatic enzymes into peritoneum
• Nephrotic syndrome / hypoalbuminemia - reduced oncotic pressure

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3. Diagnostic Paracentesis

Fluid to Send:

Gross Appearance Clues:

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4. SAAG - The Key Diagnostic Tool

Accuracy ~97% for diagnosing portal hypertension. SAAG reflects hepatic sinusoidal pressure and correlates well with HVPG (r = 0.72).

Interpreting SAAG + Ascitic Protein Together:

Exam trick: BNP elevated in serum → points to cardiac ascites (high-SAAG + high protein).

False SAAG results: Chylous ascites (falsely HIGH); serum hyperglobulinemia >5 g/dL (narrows gradient - use correction: SAAG × [0.16 × (serum globulin + 2.5)])

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5. Management of Cirrhotic Ascites

Step 1 - Mild/Moderate Ascites: Dietary + Diuretics

• Ratio maintained at furosemide:spironolactone = 40:100 (e.g., 80 mg:200 mg)
• Adjust every 3-4 days
• Goal: Weight loss 1 kg first week, then 2 kg/week subsequently
• Stop or reduce if: Weight loss >0.5 kg/day (no edema) or >1 kg/day (with peripheral edema) - risk of hypovolemia

Step 2 - Refractory Ascites (10-20% of patients)

Albumin alone acutely (without diuretics) is of no benefit and may increase risk of pulmonary edema.

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6. Spontaneous Bacterial Peritonitis (SBP)

Diagnosis:

• Ascitic PMN count ≥250/µL = diagnostic of SBP
• Cultures positive in only 40-50% of cases (inoculate blood culture bottles at bedside)
• PMN count >250 + multiple organisms → suspect secondary bacterial peritonitis (perforated viscus)

Treatment:

• IV Cefotaxime 2 g every 8-12 hours for 5 days (third-generation cephalosporin)
• IV Albumin 1.5 g/kg on day 1 AND 1 g/kg on day 3 → prevents hepatorenal syndrome, reduces mortality
• Repeat paracentesis at 48 hours - confirm PMN count decreased ≥25%
• Nosocomial SBP or critically ill → consider carbapenem (MDR organisms)

SBP Prophylaxis:

• Oral norfloxacin or ciprofloxacin (daily) for: prior SBP history, ascitic protein <1 g/dL, active GI bleeding
• IV ceftriaxone for inpatients

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7. Hepatorenal Syndrome (HRS)

• Sepsis/vasodilators (worsen vasodilation)
• GI hemorrhage, overdiuresis, diarrhea (decrease circulating volume)
• NSAIDs (renal vasoconstriction)
• Aminoglycosides (nephrotoxic)
• Volume expansion with albumin (1 g/kg/day × 2 days) must fail to improve creatinine

• Vasoconstrictors: Terlipressin (preferred) or norepinephrine + IV albumin
• Liver transplantation = definitive (HRS is a transplant priority)

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8. Hepatic Hydrothorax

• Transudation of ascites through diaphragmatic defects into pleural space (usually right-sided, ~85%)
• Manage similarly to ascites: Na restriction + diuretics
• Thoracentesis for diagnostic/symptomatic relief; repeated drainage discouraged
• TIPS if refractory

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9. Other Complications

Hyponatremia (serum Na <130 mEq/L)

• Fluid restriction to 1.5 L/day
• Tolvaptan (V2-receptor antagonist) can raise Na but not approved long-term (hepatotoxicity); use only as bridge to transplant

Hepatic Encephalopathy (HE)

• Graded I-IV; overt HE diagnosed clinically + asterixis
• Ammonia levels unreliable for grading (high >150 µmol/L supportive but non-specific)
• EEG: generalized slowing + triphasic waves
• Minimal/subclinical HE in up to 80% of cirrhotics

Hepatopulmonary Syndrome (HPS)

• Criteria: PaO2 <80 mmHg OR A-a gradient >15 mmHg + pulmonary vascular shunting on contrast echo

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10. Ascitic Fluid Analysis Summary Table

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High-Yield Exam Points

1. Cirrhosis = 84% of all ascites; paracentesis is mandatory for new-onset ascites even in coagulopathy
2. SAAG ≥1.1 = portal hypertension (97% accurate); does NOT change with diuresis
3. Cirrhosis = high SAAG + LOW protein (capillarized sinusoids don't leak protein)
4. Cardiac ascites = high SAAG + HIGH protein - the key differentiator from cirrhosis
5. SBP = ascitic PMN ≥250/µL; treat with IV cefotaxime + IV albumin (albumin prevents HRS)
6. LVP >5 L must be accompanied by albumin 6-8 g per liter removed (prevents circulatory dysfunction)
7. Spironolactone:Furosemide ratio = 100:40 (5:2); max 400:160 mg/day
8. TIPS = better than LVP at preventing ascites recurrence; more hepatic encephalopathy
9. Beta blockers should be used cautiously in refractory ascites (may reduce survival)
10. Terlipressin + albumin = treatment of HRS; liver transplant = definitive
11. Avoid NSAIDs, ACE inhibitors, ARBs in cirrhotic ascites (worsen renal perfusion)
12. Chylous ascites = milky appearance, TG >200 mg/dL; causes: lymphatic trauma, cirrhosis, tumor, TB

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