Acute and chronic neurological manifestations of acute porphyria

The neurological manifestations of acute attacks and chronic symptoms were evaluated both prospectively and retrospectively in 90 patients with acute porphyria and integrated with data from previously published series.

Most acute attacks presented with a combination of abdominal pain, mild cognitive and behavioral symptoms, and autonomic dysfunction, predominantly attributed to vagal insufficiency. Acute peripheral neuropathy and encephalopathy developed if an acute attack proceeded. Acute peripheral neuropathy emerged 1-3 weeks after the onset of an attack and was predominantly motor in nature. It was consistently associated with preceding abdominal pain (100%) and dysautonomia (100%), and frequently accompanied by central nervous system involvement (50%) and mild hepatopathy (75%). Acute encephalopathy (AE), which was transient resolving within a few days, manifested 3-19 days after attack onset. AE was characterized by a triad of seizures, confusion, and/or blurred vision. PRES was identified on MRI in 42% of patients with AE during acute attacks; among these, 88% were hyponatremic and 94% had mild hepatopathy. Of the patients with recurrent attacks, ∼40% experienced chronic symptoms. The most common clinical pattern consisted of chronic mild-to-moderate neuropathic pain, fatigue, and nausea, typically developing within the first year of cyclical attacks. All patients in this subgroup exhibited persistently elevated urinary porphobilinogen (PBG) excretion. Most patients without recurrent attacks reported no chronic symptoms. Seven patients experienced chronic neuropathic pain, fatigue, and nausea despite the absence of recurrent attacks. Only three of them exhibited persistently elevated urinary PBG excretion. They had previously demonstrated cyclical attacks that had spontaneously subsided but subsequently evolved into chronic mild pain and fatigue, often exacerbated by stress or infections, without further overt attacks. The remaining four patients had a mild increase in urinary PBG levels, and their chronic symptoms developed 3-23 years after their last documented acute attack.

The pathogenesis of autonomic and peripheral neuropathy in acute porphyria is complex; delta-aminolevulinic acid is considered a potential initiator of neuronal injury. The mechanisms underlying AE remain incompletely understood, but current evidence suggests a multifactorial process involving abrupt hypertensive episodes, SIADH, and acute metabolic or inflammatory factors of hepatic origin. Chronic symptoms are common among patients with recurrent attacks. The most effective treatment should focus on preventing recurrent attacks.