A 26-year-old female presents from home confused with a low-grade fever. Her blood pressure is 160/100 mmHg. She has no gross motor deficits on neurological examination.

Ten days prior to this presentation, she had induction of labour and delivery of a still-born foetus, at 32 weeks gestation, complicated by disseminated intravascular coagulation. She had been on labetalol for pregnancy-induced hypertension.

Her discharge medications included paracetamol, tramadol and a selective serotonin reuptake inhibitor. She has a six-year history of uncomplicated Hepatitis C infection.

a) List the differential diagnoses for her confusion and temperature.

b) Outline your approach to establishing the diagnosis.

[Click here to toggle visibility of the answers]

College Answer

a)

Pregnancy related: Eclampsia / preeclampsia / HELLP, Posterior reversible encephalopathy
syndrome (PRES), Hypertensive encephalopathy

Primary neurological: Infection (meningitis / encephalitis), cerebral venous thrombosis, seizure
disorder, other cerebro-vascular

Metabolic: Sodium (hypo/hyper), Glucose (hypo/hyper), Renal failure, Liver failure (HCV /
Paracetamol / Antidepressants),

Drugs: Accidental / intentional overdose, drug reactions (serotonin syndrome)

b)
History: Collateral, Pregnancy issues, Ongoing blood loss, bleeding / bruising, drug ingestions, mood
/ affect, headaches

Examination: BP, uterine size / discharge, oedema, meningism, neurological (tone, reflexes,
symmetry), chronic liver disease

Investigations:
FBC: Bleeding, platelets, WCC
UEC: urea / creatinine, Na, Ca, glucose
Coagulation: DIC, INR for CLD
LFT / Ammonia: hepatic encephalopathy, drug reactions ABG: hypoxia / hypercardia
Urinary drug screen / paracetamol level
Sepsis Screen, CT head +/- LP

Discussion

This works better if it is presented in the form of a table

Differential Diagnosis
of Unconsciousness and Fever
in the Pregnant Patient
Causes Investigations

Vascular causes:

  • Cerebral venous sinus thrombosis
  • PRES, hypertensive encephalopathy
  • Subarachnoid haemorrhage
  • CT brain +/- CT angiogram (venogram)
  • MRI brain

Infectious causes:

  • Meningitis 
  • Encephalitis without meningism
  • Neurological sequelae of systemic infection, eg. septic encephalopathy
  • Inflammatory markers
  • Blood cultures
  • Antenatal history, (i.e. thinking about Group A  streptococci)
  • LP, CSF microscopy and culture
  • CT brain to rule out brain abscess

Drug-related causes:

  • Paracetamol overdose with hepatic encephalopathy
  • Serotonin syndrome
  • Tramadol overdose
  • Overdose (or, just real party-style dosing) of recreational drugs
  • History  of drug abuse
  • Examination findings consistent with IVDU
  • Clinical features of  a recognisable toxidrome, eg. opiate, or classicl features of serotonin syndrome
  • Paracetamol level
  • CK, urinary myoglobin

Intrinsic neurological cause

  • Worsening of seizure disorder, associated with pregnancy (i.e. non-convulsive status epilepticus)
  • History of epilepsy
  • History or typical seizure control measures and compliance with them

Autoimmune causes

  • SLE-related Cerebral vasculitis
  • "Vasculitic screen" -ANA, ENA, ANCA, etc
  • CTA or MRA with contrast
  • ESR

Traumatic or environmental causes

  • Traumatic brain injury due to accident or non-accidental trauma 
  • Hypothermia or hyperthermia
  • History of domestic violence
  • History of exposure to the elements (eg. known to be homeless)
  • Clinical features consistent with non-accidental injury, eg. brusing at varying stages of evolution 

Endocrine and metabolic causes:

  • Hypoadrenalism
  • Hypothyroidism
  • Hepatic encephalopathy
  • Uremic encephalopathy
  • Wernicke's encephalopathy
  • Hyper or hyponatremia
  • Hyper or hypoglycamia
  • Numerous others!
  • Random cortisol
  • Short syncathen test
  • TFTs, free T3 and T4
  • EUC and CMP - for renal function and sodium
  • BSl, ketones, serum osmolality (HONK, hypoglycaemia)
  • Red cell transketolase (thiamine deficiency)
  • LFTs (acute hepatitis)
  • Coags (chornic hepatitis - synthetic function)
  • Ammonia level (hepatic encephalopathy, valproate overdose)
  • ABG (hypoxia, hypercapnea, acidosis of other causes)

Differentials specific to pregnancy:

  • Eclampsia or preeclampsia
  • HELLP
  • Historic details of antenatal care, eg. has anybody tested for proteinuria

References

Oh's Intensive Care manual: Chapter 63   (pp. 677) Preeclampsia  and  eclampsia by Wai  Ka  Ming  and  Tony  Gin

RCOG Guidelines for the management of severe pre-eclampsia/eclampsia (2006)

Duckitt, Kirsten, and Deborah Harrington. "Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies." Bmj 330.7491 (2005): 565.

Lorquet, Sophie, et al. "Aetiology and physiopathology of preeclampsia and related forms." Acta Clinica Belgica 65.4 (2010): 237-241.

Young, Brett C., Richard J. Levine, and S. Ananth Karumanchi. "Pathogenesis of preeclampsia." Annual Review of Pathological Mechanical Disease 5 (2010): 173-192.

Altman, D., et al. "Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial."Lancet 359.9321 (2002): 1877-1890.

Beach, Robert L., and Peter W. Kaplan. "Seizures in pregnancy: diagnosis and management." International review of neurobiology 83 (2008): 259-271.

Walker, S. P., M. Permezel, and S. F. Berkovic. "The management of epilepsy in pregnancy." BJOG: An International Journal of Obstetrics & Gynaecology116.6 (2009): 758-767.

Chen, Yi-Hua, et al. "Affect of seizures during gestation on pregnancy outcomes in women with epilepsy." Archives of neurology 66.8 (2009): 979-984.

Otani, Koichi. "Risk factors for the increased seizure frequency during pregnancy and puerperium." Psychiatry and Clinical Neurosciences 39.1 (1985): 33-42.

Teramo, K., et al. "Fetal heart rate during a maternal grand mal epileptic seizure." Journal of Perinatal Medicine-Official Journal of the WAPM 7.1 (1979): 3-6.

LaJoie, Josiane, and Solomon L. Moshé. "Effects of seizures and their treatment on fetal brain." Epilepsia 45.s8 (2004): 48-52.

Klein, Pave, and Andrew G. Herzog. "Hormonal effects on epilepsy in women."Epilepsia 39.s8 (1998): S9-S16.

Vajda, Frank JE, et al. "Seizure control in antiepileptic drug‐treated pregnancy." Epilepsia 49.1 (2008): 172-176.