Transient Cortical Blindness and
Bioccipital Brain Lesions in Two
Patients with Acute Intermittent
Porphyria
Hugo Kupferschmidt, MD; Adriano Bont, MD;
Hans Schnorf, MD; Theodor Landis, MD;
Eike Walter, MD; Jurg Peter, MD;
Stephan Krahenbuhl, MD, PharmD;
and Peter J. Meier, MD
Ann Intern Med. 1995;123:598-600.

1 he most common neurologic manifestations of acute
intermittent porphyria are autonomic visceral neuropathy,
peripheral motor neuropathy, and central nervous system
dysfunctions, including seizures and neuropsychiatric disturbances (1). In rare instances, however, patients with
acute intermittent porphyria have presented with acute
cortical blindness (2-5), for which deleterious vasospasm
in both posterior cerebral arteries has been inferred (3,6).
We describe two patients in whom cortical blindness
was the first symptom of acute intermittent porphyria.
Magnetic resonance imaging showed extensive lesions involving primarily white matter of both occipital lobes
consistent with vasospasm-induced ischemic lesions. However, the pathogenesis of the suspected vasospasm in
acute intermittent porphyria is unknown. Because the enzyme nitric oxide synthase is a hemoprotein (7) and nitric
oxide is a major vascular dilator (8), we hypothesize that
severe heme deficiency during acute attacks may cause
unopposed cerebral vasoconstriction due to a decrease in
cerebral nitric oxide production.
From University Hospital, Zurich; University Hospital, Basel; and University Hospital, Geneva, Switzerland. For current author addresses, see end
of text.

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Figure 1. T2-weighted axial magnetic resonance images in Patient 1. Large confluent areas of signal hyperdensities are present in the
occipital cortex, including the calcarine cortex, and in the adjacent white matter.
Case Reports
Patient 1
A 35-year-old woman was hospitalized because of sudden loss of vision. With the exception of a brother with
partial porphobilinogen deaminase deficiency, she had no
family history of porphyria, and she had no known exposure to porphyrinogenic drugs. At admission, she appeared to be blind, was unable to see or fixate on any
target (although she reacted to large moving targets), and
could not see colors. The remainder of the neurologic
examination was normal.
During the patient's first day in the hospital, she had
two tonic-clonic seizures and was treated with carbamazepine and phenytoin. Computed tomography and magnetic resonance imaging showed multifocal lesions primarily in both occipital lobes (Figure 1). During the next
14 days, her vision was completely restored, but she developed flaccid tetraplegia. Electroneuromyography showed a
pure axonal motor neuropathy. Routine biochemical assessments of serum and cerebrospinal fluid were normal.
Urinary excretions of (8-aminolevulinic acid (788 /miol/d;
normal, <50 /xmol/d), porphobilinogen (1346 jutmol/d; normal, < 8 jbtmol/d), uroporphyrin (369 nmol/d; normal, <60
nmol/d) and coproporphyrin III (701 nmol/d; normal, <200
nmol/d) were markedly increased. A diagnosis of acute
intermittent porphyria was made and was confirmed by
decreased porphobilinogen deaminase activity in lysed
erythrocytes (51 pmol/h per mg protein; normal range, 60
to 150 pmol/h per mg protein). Plasma lead level was not
elevated. She was treated with intravenous glucose (500
g/d) and hematin (4 mg/kg body weight per day; three
6-day courses of daily infusions over a 7-week period),
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and the biochemical and clinical signs of acute intermittent porphyria improved during the following 2 months.
However, 6 months after the initial presentation, magnetic resonance imaging showed residual ischemic lesions
in the bioccipital white matter. One year after the initial
presentation, the patient had completely recovered.
Patient 2
A 32-year-old woman with no family history of acute
intermittent porphyria and with no known exposure to
porphyrinogenic drugs had abdominal hysterectomy because of a myoma. No known porphyrinogenic drugs were
used for anesthesia. After this surgery, she had severe
persisting abdominal pain and developed arterial hypertension (170/100 mm Hg), tachycardia (110 beats/min)
and three generalized tonic-clonic seizures, for which she
received phenytoin. She suddenly became blind but was
unaware of her blindness (Anton syndrome [9]) and could
correctly guess the direction of moving lights (Riddoch
phenomenon [10]).
Axial Tx-weighted magnetic resonance images were
compatible with cortical swelling, and T2-weighted images
showed several, probably ischemic, lesions in the white
matter of both occipital lobes and the right frontal lobe
(Figure 2). On the basis of increased urinary excretion of
8-aminolevulinic acid (526 /u-mol/d) and porphobilinogen
(698 /xmol/d), a diagnosis of acute intermittent porphyria
was made. Plasma lead level was not measured. After the
patient received treatment with intravenous glucose (300
g/d) and heme-arginate (3 mg/kg per day; two 6-day
courses of daily infusions over a period of 3 weeks), visual
disturbances improved, but peripheral motor neuropathy
• Annals of Internal Medicine • Volume 123

• Number 8

599

Figure 2. T2-weighted axial magnetic resonance images in Patient 2. Patchy hyperdensities are present in both occipital lobes and in
the precentral and frontal subcortical white matter. Additionally, right paracentral white matter hyperdensities are present (left and
middle panels). Tj-weighted coronal sections show gadolinium enhancement along cortical gyri and sulci in the occipital paracentral
cortex. Slight contrast enhancement of the left calcarine cortex is also present (right panel).

developed, progressing rapidly to flaccid tetraparesis. Urinary excretion of porphyrin precursors returned to normal
after 3 weeks of therapy with intravenous heme-arginate
and high-dose glucose. However, 4 weeks later, magnetic
resonance imaging showed only minimal improvement.
Vision returned to normal within 3 weeks, and the tetraparesis improved within 8 months to the point that the
patient was able to resume an independent lifestyle.
Discussion
During the last 10 years, we have seen 18 patients with
severe attacks of acute intermittent porphyria. Of these,
the 2 patients described here were the only ones who
presented with transient cortical blindness, repetitive tonic-clonic seizures, and a severe peripheral motor neuropathy. Furthermore, magnetic resonance imaging in both
patients showed cerebral abnormalities consistent with
bioccipital ischemic brain lesions. These observations support the concept that multifocal ischemia and cerebral
microinfarctions, possibly resulting from porphyria-induced vasospasms, may be important causes of cerebral
dysfunction during acute attacks of acute intermittent
porphyria (3, 5, 6).
That bilateral spreading cerebral hypoperfusion (11)
and occipital magnetic resonance imaging (12) are found
in patients with migraine-associated visual disturbances
supports the idea that the magnetic resonance imaging
abnormalities seen in our two patients may have resulted
from vasospasm-induced ischemia. However, the pathogenesis of the suspected cerebral vasoconstriction in acute
intermittent porphyria is unknown. Interestingly, the recently characterized enzyme nitric oxide synthase is a
cytochrome P-450 type hemoprotein (7) whose activity
may be reduced in situations of decreased heme production such as acute intermittent porphyria. Because nitric
oxide is an established and important vasodilator in the
central nervous system (8), decreased cerebral nitric oxide
production in patients with acute intermittent porphyria
600

may be associated with unopposed cerebral vasoconstriction, potentially leading to lesions in brain areas that are
particularly vulnerable to hypoxia.
Requests for Reprints: Peter J. Meier, MD, Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital CH8091, Zurich, Switzerland.
Current Author Addresses: Drs. Kupferschmidt, Krahenbiihl, and Meier:
Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH-8091, Zurich, Switzerland.
Dr. Bont: Neurologische Universitatsklinik, Kantonsspital, Petersgraben 4,
CH-4031, Basel, Switzerland.
Drs. Schnorf and Landis: Hopital Cantoral de Gueve, Service de Neurologic Rue Hicheli du Crest 24, 1211, Geneve, 14, Switzerland.
Dr. Walter: Medizinische Universitatskinik, Abt. Innere Medizin II, Hugstetter StraBe 55, D-79106, Freiburg, Germany.
Dr. Peter: Spital Limmattal, 8952 Schlieren, Medizinische Abteilung, Switzerland.

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