An acutely confused young woman

Abstract

In September, 2009, a 20-year-old previously healthy woman presented to our emergency department with altered mental status, right arm tingling and numbness, and a bilateral pulsating frontotemporal headache. Her symptoms had started several hours earlier with transient loss of consciousness. On examination, she was alert, with reduced concentration, incoherent thoughts, and poor recall for recent events. There was no evidence of localising neurological signs or neck stiff ness. Her temperature, blood pressure, and vital signs were normal. Abuse of alcohol or illicit substances was denied by a friend who accompanied the patient. Her personal and family history was negative for seizure disorders, migraine, and vascular risk factors. CT of the brain and haematological, biochemical, and cerebrospinal fl uid examination were normal. MRI of the brain, 20 h after the onset of her symptoms, showed multiple confl uent areas of abnormal high signal intensity on T2-weighted scans, symmetrically involving juxtacortical white matter of the frontal, parietal, occipital, and temporal lobes. In these areas, diff usion coeffi cient maps, generated by diff usion-weighted imaging, showed an elevated diff usion suggestive of vasogenic oedema (fi gure A, C, and webappen dix). A diagnosis of posterior reversible enceph alopathy syndrome (PRES) was suspected, and confi rmed by the almost complete disappearance of MRI abnormalities a week later. PRES is clinically characterised by confusion, headache, altered consciousness, seizures, and visual disturbance, with MRI changes of often widespread vasogenic oedema typically predominating in the occipitoparietal regions. PRES is commonly associated with hypertensive encephalopathy, eclampsia, kidney disease, hypercal caemic crisis, autoimmune disorders, transplantation, sepsis, and immunosuppressive treatment or chemo therapy. The pathophysiology is poorly understood, although the ultimate underlying process seems to be an increase in capillary hydrostatic pressure or endothelial dysfunction with a breakdown of the blood–brain barrier triggered by diff erent systemic conditions. Surprisingly, our patient’s history and examinations did not identify any known cause of PRES. However, when suffi ciently recovered for an in-depth interview, she reported sniffi ng an unknown dose of “poppers” (nitrite inhalants) for the fi rst time, just before the onset of symptoms. The close temporal association between inhalation and the onset of the neurological features suggested a causal relation. Over the next 24 h she progressively and spontaneously recovered, returning to normal within a day. In October, 2009, at fi nal follow up MRI was normal (fi gure B, D). Nitrite inhalants act through generation of nitric oxide, which activates soluble guanylyl cyclase, stimulating the production of cyclic guanosine monophosphate (cGMP), which leads to vasorelaxation via cGMP-dependent protein kinases. Vasodilation can cause the common adverse eff ects—a drop in systemic blood pressure, increased heart rate, headache, and fainting. Donors of nitric oxide are well known to cause headache and trigger migraine attacks in people who have migraines. However, PRES has not been previously described as a consequence of use of nitrite inhalers, despite their widespread use as therapeutic, diagnostic, or recreational agents. Glyceryl trinitrate was reported to aggravate pre-eclamptic PRES in one case. Nitric oxide donors dilate veins and arteries, modifying intracranial haemodynamics and resulting in an imbalance between forces that govern fl uid motion into and out of the microvasculature. We suggest in our patient’s case, that this intense vasodilation might have promoted vascular instability, breakdown of the blood–brain barrier, and fl uid extravasation. Club-drug toxic eff ects should be considered in the diff erential diagnosis when a previously healthy individual (typically a young adult) presents with an acute change in mental status. Accurate drug history and a good knowledge of adverse eff ects of individual street drugs is important for the generalist clinician to eff ectively face the diagnostic and therapeutic challenges they pose. The growing list of causes of PRES should perhaps include nitrite inhalants.