Cyanide poisoning

Cyanide poisoning is a cause of an acute anoxic-ischaemic encephalopathy that also has eventual chronic sequelae. 

Epidemiology

Acute cyanide poisoning is rare and often occurs after suicidal oral ingestion of cyanide-containing compounds, however there are other sources such as after smoke inhalation ^1,2. Chronic cyanide poisoning is generally related to occupational exposure, such as working in the metal industry ¹.

Clinical presentation

Patients can present with a variety of devastatingly disabling clinical features, often manifesting within minutes of exposure ^1-5:

• headache
• seizures
• agitation
• cardiac arrhythmias
• cardiac and respiratory arrest, often leading to coma and rapid death

If a patient survives the acute poisoning, eventual chronic neurological sequelae include the development of movement disorders (e.g. parkinsonism, choreoathetosis, dystonia), or rarely, the development of memory impairment ^1-5.

Pathology

A cyanide is a compound, known simply as a 'cyanide', that contains a cyanide group (CN^-) ^1,3-6. These compounds include solids, typically cyanide salts (e.g. potassium cyanide), liquids or gases (e.g. hydrogen cyanide), which can cause toxicity through ingestion, dermal absorption, or inhalation ^1,3-6. It is highly toxic, with the mean lethal dose of potassium cyanide only being 3 mg/kg ¹.

Cyanide is a respiratory chain metabolism toxin that inhibits the mitochondrial enzyme cytochrome c oxidase, a terminal enzyme of the respiratory electron transport chain ^1,3-6. This culminates in cytotoxic anoxia in cells, especially those that have high oxygen requirements ^1,3-6. In the brain, the structures that require the highest oxygen requirement, namely the basal ganglia and cerebral cortex, are the regions most prominently affected by this anoxic toxicity ^1,3-6. Thus, the basal ganglia undergoes haemorrhagic necrosis and the cortex undergoes pseudolaminar necrosis ^1,3-6. Notably and unusually, despite its rich oxygen supply, the hippocampi are characteristically spared in this process ^1,3-6.

Radiographic features

Cyanide poisoning characteristically tends to bilaterally affect the basal ganglia, especially the striatum, and the cerebral cortex, especially the sensorimotor cortex ^1,3-6. However, in severe cases that lead to rapid death, more widespread changes, including diffuse cerebral oedema, can be seen ⁷.

CT

Classically seen as hypoattenuation bilaterally in the basal ganglia, reflective of necrosis. These areas may or may not have evidence of hyperattenuating macroscopic haemorrhage ⁵. Cortical changes are often not evident on CT ⁵.

MRI

Regions of involvement are identical to those involved on CT, but are appreciated in greater detail. Signal characteristics of the necrosis in the acute setting include ^1,3,4,7:

• T1: generally high signal, consistent with pseudolaminar necrosis when affecting the cortex, but also due to presence of haemorrhage
• T2/FLAIR: affected areas demonstrate high signal that become more pronounced within weeks
• T1 C+ (Gd): usually vivid contrast enhancement
• DWI: affected areas show increased diffusion signal

In the chronic phase after acute cyanide poisoning, a decrease of high signal intensity in all sequences is generally appreciated, but this may take more than a year to occur ^1,3. Unlike other toxic encephalopathies, such as methanol poisoning, cystic sequelae usually do not eventuate ³.

Treatment and prognosis

Treatment generally involves administration of antidotes such as hydroxycobalamin, which binds to cyanide compounds to create non-toxic compounds that can be safely excreted by the kidneys ². Another commonly used antidote is sodium thiosulphate, which accelerates the metabolism of cyanide to less toxic derivatives ². 

The prognosis of acute cyanide poisoning is very grim, with a 95% mortality rate ¹.

Differential diagnosis

For involvement in and around the basal ganglia, consider:

• mitochondrial encephalopathies
  • Leigh disease
  • Kearns-Sayre syndrome
• other toxic encephalopathies
  • carbon monoxide neurotoxicity
  • methanol neurotoxicity
  • organophosphate neurotoxicity
• metabolic disorders
  • Wilson disease
• prion encephalopathies
  • Creutzfeldt-Jakob disease