Eclampsia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Seizures during pregnancy that are unrelated to Preeclampsia need to be distinguished from Eclampsia. This is essential to recognize the correct cause and provide the targeted treatment necessary in a timely manner.

Differentiating Eclampsia from other Diseases

Eclampsia must be differentiated from other diseases that can cause seizures during pregnancy. The differentiation can be done by obtaining a proper history, physical examination, diagnostic tests, or imaging. Such disorders include:

• Acute exacerbation of systemic lupus erythematous
• Adrenal Insufficiency or Acute Adrenal crisis
• Aneurysm of the brain
• Brain tumor
• Cerebellar Haemorrhage
• Disseminated herpes simplex/ Herpes Simplex Encephalitis (HSE)
• Disseminated sepsis syndromes
• Drug Overdose syndromes
• Drug Withdrawal syndromes
• Encephalitis
• Acute Fatty liver of pregnancy (AFLP)
• Hemolytic uremic syndrome (HUS)
• Hypertensive encephalopathy
• Hypoglycemia
• Medication- or drug-induced seizures
• Meningitis
• Posterior reversible encephalopathy syndrome (PRES)
• Primary Hyperaldosteronism
• Seizure disorders and Epilepsy
• Stroke (Hemorrhagic or Ischemic)
• Thrombotic thrombocytopenic purpura

Usually, the presence of the signs of severe preeclampsia that precede and accompany eclampsia facilitates the diagnosis.

Differential Diagnosis	Similar Features	Differentiating Features
Acute exacerbation of SLE	Lupus flares can present with proteinuria, hypertension, deterioration in kidney function, thrombocytopenia and seizure also observed in eclampsia.	On urine examination, cellular casts and proteinuria can be found in SLE while only proteinuria is seen in Eclampsia. SLE is associated with decreasing levels of complement and incresing titre of anti-dsDNA. Also, a history of previous SLE and onset of symptoms before 20 weeks points towards lupus and a renal biopsy can help confirm the diagnosis although it is genereally not recommended during pregnancy.
Acute adrenal insufficiency	Adrenal insufficiency can present with fatigue, nausea, vomiting, increased heart rate, increased respiratory rate, loss of appetite, headache, abdominal pain, confusion, loss of consciousness, abnormal body movements, or coma, also seen in eclampsia.	Adrenal insufficiency will present with hypotension, whereas eclampsia is associated with high blood pressure. Also, AI patients may have a history of chronic use of steroids for diseases such as asthma, rheumatoid arthritis, etc. Patients may present with symptoms only in the postpartum period as during pregnancy they may acquire cortisol transplacentally from the fetus. Diagnostic tests show decreased morning basal serum cortisol, decreased salivary free cortisol, not seen in eclampsia. Further cosyntropin test and basal ACTH levels can be done. Imaging (MRI without gadolinium administration should be done in pregnant women) may show a pituitary tumor or a cranial SOL.
Brain tumor(s)	Brain tumor often presents with signs of raised Intracranial pressure, such as headache, nausea, vomiting and seizures, also seen in eclampsia. Commom tumors that can be found are meningiomas, pituitary tumors, gliomas, etc.	Presence of past history of convulsions and absence of hypertension and proteinuria points towards cerebral pathology. Brain tumour may present with partial or localized seizures rather than GTCS and can have localized symptoms, such as visual disturbances in pituitary adenomas, localized sensory or motor changes, etc which could differentiate it from eclampsia. Also, brain imaging such as MRI can help establish the diagnosis.
Intracranial Haemorrhage/ Ruptured Brain Aneurysm	On physical exam, history and diagnostic test, ICH demonstrates headache, nausea and vomiting, vision abnormalities(such as blurring, scotomas, diminished vision), seizures, loss of consciousness also observed in Eclampsia.	The headache in ICH is often described as the worst headache of life. Presence of symptoms such as stiffness of neck, sensitivity to light, unilateral drooping of eyelid, unilateral symptoms of stroke(sensory or motor weakness), and absence of proteinuria, oliguria, edema, gestational hypertension differentiates its from Eclampsia. Neuroimaging (CT or MRI brain) will show AV malformation, ruptured blood vessel, blood in the subarachnoid space that distinguish it from Eclampsia.
Disseminated herpes simplex/ Herpes Simplex Encephalitis(HSE)	On physical exam and history Herpes Simplex Encephalitis(HSE) may present with Headache, Seizures( seen in 50% of cases ), vision abnormalities, confusion, hyperactivity also observed in eclampsia.	On physical exam and history Herpes Simplex Encephalitis(HSE) demonstrates high fever, stiff neck, altered reflexes, drowsiness with stupor, localised symptoms such as aphasia, anosmia that distinguish it from [eclampsia]. Also, skin lesions in dermatomal distribution, immunocompromised status, retinitis points towards HSE. Detection of DNA or Zoster Antigen in CSF and Polymerase chain reaction(PCR) on CSF confirms infection with HSV. Treatment with antivirals(acyclovir) results in dramatic improvement.
Drug overdose/Drug Intoxication	On physical exam and history drug intoxication can present with Seizures, Hypertension, nausea and vomiting also observed in eclampsia. The most common drugs accountable for seizures include Antidepressants, Diphenhydramine, Stimulants(Cocaine, Methamphetamines) Tramadol, and isoniazid.	Careful history and past records will indicate if the patient is taking any recreational or prescriptional medication respectively that could lead to overdose. Other symptoms of preeclampsia like proteinuria, edema are generally absent. Urine drug screening and Blood screening will confirm the diagnosis.
Drug Withdral Syndromes	Drug Withdral Symptoms are precipitated by sudden absence of a drug from one's system after development of physiological dependence on the drug. They could include Hypertesnion, tremors , seizures(GTCS), agitation, nausea and vomiting, also seen in eclampsia. Common responsible agents include, Short acting opoids(such as Heroin, some painkillers), Long acting opoids(eg.methadone), benzodiazepines(eg. clonazepam, Xanax), Alcohol.	Presence of past history of drug intake, and symptoms like anxiety, insomnia, hallucinations, Psychological disturbances, Diarrhea(Benzodiazepines), Delerium Tremens(alcohol withdrawal), frequent yawning, goosebumps, body aches(opioids) point towards drug withdrawal. A urine drug screen helps confirm the diagnosis.
Encephalitis	Encephalitis, inflammation of the brain, is most often caused by viral infection , presents with seizures in 2-67% of cases , and headache also seen in eclampsia.	On history and physical exam a patient with Encephalitis demonstrates: fever, stiff neck, sensitivity to light, increased drowsiness, confusion and disorientation, irritability, anxiety and if severe: weakness, partial paralysis, double vision, impaired speech or hearing, coma, psychosis, hallucinations, etc. often not seen in eclampsia. Neuroimaging (brain MRI or CT scan), PCR or a lumbar puncture (spinal tap) is performed to check for signs of infection. Eg. if the cause is viral, the CSF will show: moderately elevated protein (60-80 mg/dL), normal glucose, and a moderate pleocytosis (up to 1000 leukocytes/µL)(Mononuclear cells usually predominate). Blood, urine and stool tests to look for organisms or antibodies responsible for an infection often helps establish diagnosis.
Acute Fatty Liver of Pregnancy (AFLP)	On history and physical exam AFLP demonstrates nausea and vomiting (seen in 50-60%), abdominal pain (50-60%), edema, mental status changes (altered sensorium, confusion, disorientation, psychosis, restlessness, seizures or coma) (60–80%), tachycardia (50%) also seen in eclampsia.	Presence of Disseminated intravascular coagulation (55% cases), jaundice (>70%), gastrointestinal bleeding ( seen in 20–60% cases), acute renal failure (seen in 50% cases), Oliguria (seen in 40–60% cases), fever(late onset) and absence of hypertension, proteinuria differentiates it from eclampsia. Abdominal pain is usually right upper quadrant, midepigastric or radiating to back in AFLP(seen in 50-60% cases) and mostly epigastric and non radiating in eclampsia. Severe coagulopathy such as disseminated intravascular coagulation is rare in pre-eclampsia but the prevalance is 55% in AFLP. Lab tests in AFLP shows raised, hyperbilirubinemia, hypoglycemia, elevated ammonia, leukocytosis and thrombocytopenia, prolonged PT and hypofibrinogenemia if DIC is present, which differentiates it from eclampsia.