Cough headache as a presenting feature of posterior reversible encephalopathy syndrome (PRES)

Discussion

Cough headache is a well described, but rare headache.¹ Headaches are characteristically triggered by a rapid increase in intra-abdominal pressure which occurs with coughing, sneezing or straining. Two types of cough headache are described: primary and secondary (symptomatic) cough headache. Primary cough headache is defined by the International Headache Society (IHS) as a headache, precipitated by coughing or straining in the absence of any intracranial disorder and lasting up to 30 minutes.² Almost any other type of underlying headache (such as migraine or tension type headache) can be exacerbated by coughing, but are not included in the rubric of cough headache. Secondary (symptomatic) cough headache (SCH) comprises around 40% of cough headaches and is associated with a wide variety of aetiologies. Prominent among them are posterior fossa lesions and Chiari malformations, which account for nearly 80% of SCH (Box 1).³

PRES is a characterised by headache, seizures, altered mental status or cortical visual disorders (such as cortical blindness and hemianopsia). Headaches are reported in up to 50% of patients with PRES. Most often, headaches are diffuse and gradual in onset, or of the thunderclap variant (in which MR angiography changes of reversible cerebral vasoconstriction accompany PRES). Cough headache has not been described in PRES.

MRI shows white matter vasogenic oedema predominantly affecting the subcortical and cortical regions of the occipito-parietal lobes, however, oedema can involve the cerebellum, brainstem or even frontal regions in more severe cases.⁴ These changes are well appreciated on T2 or T2-FLAIR MRI sequences. Severe PRES can lead to cerebral infarction or haemorrhage. Prompt recognition and treatment of the underlying condition can lead to good outcomes and reversibility of the MRI changes on follow-up. Most patients experience a good outcome within weeks, although up to 15% of patients can develop morbidity or mortality with severe PRES.

PRES is associated with hypertension only in 70–80% of cases. Although the exact pathophysiological mechanisms are unclear, hypertension and endothelial dysfunction are key components in many cases. Other triggers of PRES include eclampsia (5–15%), renal failure (~0.35–0.5%), autoimmune disorders (5–10%), sepsis (5–15%) and use of medications, of which, immunosuppressants, chemotherapeutic agents (20–60%) and RhEPO are well-known culprits.⁵ Acute or chronic endothelial dysfunction, loss of cerebral autoregulation, endothelial cell inflammation and attack by antigen-antibody complexes or cytokines can all lead to PRES by impairing the blood–brain barrier and causing vasogenic oedema.⁶ All these insults initiate a compensatory vasoconstrictive cerebral autoregulatory response which mitigates damage to some extent. However, the posterior circulation arteries of the brain lack a robust sympathetic innervation compared with the anterior circulation (the sympathetic nerves travel intracranially along the internal carotid artery into the cranial cavity). This partly explains the posterior predominance of PRES.

RhEPO which is commonly prescribed to patients with end-stage renal disease (ESRD) for treatment of an underlying normocytic anaemia, is well known to exacerbate hypertension in patients with ESRD as well as contribute to endothelial dysfunction. Fortunately, recurrences of PRES are rare, even when patients are re-exposed to the same insults.⁷ PRES is an important differential diagnosis in patients with a new onset cough headache.