A severe, rapidly advancing, more or less symmetrical and mainly motor polyneuropathy—often with abdominal pain, psychosis (delirium or confusion), or convulsions—may be a manifestation of acute intermittent porphyria. This type of porphyria is inherited as an autosomal dominant trait and is not associated with cutaneous sensitivity to sunlight. The metabolic defect is in the liver and is marked by increased production and urinary excretion of porphobilinogen and of the porphyrin precursor Δ-aminolevulinic acid. The peripheral and central nervous systems may also be affected in another hepatic type of porphyria (the variegate type). In the latter, the skin is markedly sensitive to light and trauma, and porphyrins are at all times found in the stools. Both of these hepatic forms of porphyria must be distinguished from the rarer erythropoietic (congenital photosensitive) porphyria, in which the nervous system is not affected.
The classic study of acute intermittent porphyria was made by Waldenstrom in 1957. The initial and often the most prominent symptom is moderate to severe colicky abdominal pain. It may be generalized or localized and is unattended by rigidity of the abdominal wall or tenderness. Constipation and intestinal distention (ileus) are frequent. Attacks last for days to weeks and repeated vomiting may lead to inanition. In latent forms, the patient may be asymptomatic or complain only of slight dyspepsia.
The disease can be identified after some time by its characteristic recurrent attacks, often precipitated by drugs such as sulfonamides, griseofulvin, estrogens, barbiturates, phenytoin, and the succinimide anticonvulsants. The possibility of sensitivity to these drugs must always be kept in mind when convulsions are being treated in the porphyric patient. The first attack rarely occurs before puberty, and the disease is most likely to threaten life during adolescence and early adulthood. In contrast, acute polyneuropathy that appears for the first time in midor late adult life is not likely to be porphyric.
The neurologic manifestations are usually those of an acute polyneuropathy involving the motor nerves more severely than the sensory ones; less often, both sensory and motor nerves are affected more or less equally and sometimes autonomic nerves as well. The symptoms may begin in the feet and legs and ascend, or they may begin in the hands and arms (sometimes asymmetrically) and spread in a few days to the trunk and legs. Often, the weakness predominates in the proximal muscles of the limbs and limb girdle muscles, in which case there is loss of knee jerks with preservation of reflexes at the ankles. Sensory loss, often extending to the trunk, is present in half the cases. Facial paralysis, dysphagia, and ocular palsies are features of only the most severe cases. The CSF protein content is normal or slightly elevated.
The course of the polyneuropathy is variable. In mild cases the symptoms regress in a few weeks. Severe cases may progress to a fatal respiratory or cardiac paralysis in a few days, or the symptoms may advance in a saltatory fashion over several weeks, resulting in a severe sensorimotor paralysis that improves only after many months.
A disturbance of cerebral function (confusion, delirium, visual field defects, and convulsions) is likely to precede the severe, but not always the mild, forms of polyneuropathy, or there may be none of these central features. Cerebral manifestations subside in a few days or weeks, although one of our patients was left with a lasting homonymous hemianopia. Tachycardia and hypertension are frequent in the acute phase of the disease and fever and leukocytosis may occur in severe cases. In general, the prognosis for recovery is excellent, although relapse of the porphyria may result in cumulative damage to the peripheral nervous system (see discussion further on under “Diagnosis of Recurrent or Relapsing Polyneuropathy”).