Differential Diagnosis for Intermittent Pinpoint Pupils

Single Most Likely Diagnosis

• Opioid use or overdose: Intermittent pinpoint pupils are a classic sign of opioid use. Opioids cause pupillary constriction, and the intermittent nature could be due to varying levels of opioid in the system or the body's adaptation and fluctuation in response to opioid use.

Other Likely Diagnoses

• Pontine stroke or lesion: The pons is part of the brainstem that controls pupil size among other functions. A lesion or stroke in this area can lead to pinpoint pupils due to disruption of the pupillary dilation pathways.
• Horner's syndrome: This condition results from disruption of the sympathetic nerves supplying the eye and can cause miosis (pupillary constriction), ptosis (eyelid drooping), and anhidrosis (lack of sweating) on the affected side of the face.
• Cluster headaches: During cluster headache episodes, patients may exhibit Horner's syndrome on the same side as the headache, which includes miosis.

Do Not Miss Diagnoses

• Subarachnoid hemorrhage: Although less common, a subarachnoid hemorrhage can cause pinpoint pupils due to increased intracranial pressure affecting the brainstem. This is a medical emergency.
• Serotonin syndrome: This is a potentially life-threatening medical condition resulting from an excess of serotonin in the central nervous system. It can cause a variety of symptoms including changes in pupil size.
• Neuroleptic malignant syndrome: A rare but life-threatening side effect of neuroleptic drugs, characterized by fever, muscle stiffness, and altered mental status, which can also present with pupillary abnormalities.

Rare Diagnoses

• Argyll Robertson pupils: A condition where pupils constrict when focusing on a near object (accommodate) but do not react (or react poorly) to light. This is often associated with neurosyphilis but can be seen in other conditions affecting the midbrain.
• Diencephalic lesions: Lesions in the diencephalon (the posterior part of the forebrain) can affect the pupillary light reflex and cause abnormal pupil sizes, including miosis.
• Familial amyloid polyneuropathy: A rare group of genetic disorders caused by mutations in the TTR gene, leading to accumulation of amyloid in various tissues, including the autonomic nervous system, which can result in pupillary abnormalities.