Photo Quiz

Cerebellar and Retinal Vascular Lesions in a Postpartum Patient

jeffrey l. olson, m.d., jeffrey bennett, m.d., ph.d., and naresh mandava, m.d.
Rocky Mountain Lions Eye Institute, University of Colorado School of Medicine, Aurora, Colorado

Figure 1.

Figure 2.

A 26-year-old woman presented with visual changes in her left eye and difficulty walking. She had given birth three months earlier and had noted the enlargement of a scotoma in the temporal visual field of her left eye during pregnancy. She also complained of intermittent paresthesias in her right arm. Her medical history was notable for central nervous system (CNS) hemangioblastomas of the cerebellum and spinal cord at level C7-T1 resected three years earlier. Furthermore, she had previously undergone a partial left nephrectomy for renal cell carcinoma.

Neurologic examination revealed intact cranial nerves, normal results on strength and sensory examinations, unsteady gait with difficulty performing tandem walk, and a positive result on Romberg's test. On ophthalmic examination, the patient had bilateral 20/30 vision without correction, which was unchanged from three years earlier; the sclera, conjunctiva, cornea, iris, and lens appeared normal. Dilated fundus examination showed a large, exophytic tumor in the left eye. The image of the peripheral fundus demonstrated this large retinal capillary hemangioma, with a dilated feeder arteriole and draining venule (Figure 1). Exudate, seen as yellowish subretinal deposits, had caused localized retinal detachment.

Magnetic resonance imaging of the brain revealed multiple enhancing nodules throughout the cerebellum consistent with hemangioblastomas (Figure 2). Edema was noted bilaterally in the cerebellum, with mild mass effect on the lateral aspect of the fourth ventricle. Postsurgical changes also were noted in the cerebellum.

Based on the patient's symptoms, history, physical examination, and neuroimaging results, which one of the following is the most likely diagnosis?

A. Ataxia-telangiectasia.

B. Sturge-Weber syndrome.

C. Tuberous sclerosis.

D. von Hippel-Lindau disease.

E. Wyburn-Mason's syndrome.

Discussion

The correct answer is D: von Hippel-Lindau disease. In 1904, von Hippel, a German ophthalmologist, described two patients with retinal angiomatosis,1 and in 1926, Lindau, a Swedish neurologist, described an association among retinal angiomatosis, hemangiomatous cysts of the cerebellum, and the visceral components of the disease.2 The transmission of von Hippel-Lindau disease is as an autosomal dominant trait with irregular penetrance.3

Cerebellar hemangioblastoma is the characteristic CNS lesion. In a study of 152 patients with von Hippel-Lindau disease, cerebellar hemangioblastomas were present in 60 percent of the patients.4 Hemangioblastomas also may occur in the medulla oblongata and spinal cord. Progressive enlargement of tumors associated with von Hippel-Lindau disease during pregnancy has been described for CNS lesions5 and retinal lesions.6 Renal cell carcinoma occurs in approximately one fourth of affected patients.7 The main causes of death are metastatic renal cell carcinoma and complications from CNS hemangioblastomas.

In published case series, pheochromocytoma occurs in 3 to 10 percent of patients, with a tendency to cluster in families.8 Other visceral manifestations include renal cysts, pancreatic cysts, neuroendocrine tumors, adenomas of the epididymis and the kidneys, endolymphatic sac tumors of the inner ear, and hepatic and epididymal cysts. Typically asymptomatic, these lesions may help diagnose von Hippel-Lindau disease.9

The ophthalmic manifestations are often among the first to be diagnosed. Retinal capillary hemangiomas may develop in 40 to 60 percent of patients with von Hippel-Lindau disease. Although the hemangiomas may be present at birth, they typically are not detected until the second or third decade of life because of their small size and peripheral location.10 Treatment depends on the location and size of the lesions. Small lesions and those touching the optic nerve are more likely to be observed.11 Larger lesions may be treated with laser photocoagulation, cryotherapy, or photodynamic therapy. The visual prognosis for patients with retinal capillary hemangioma is guarded, especially with large, untreated lesions.

Patients with ataxia-telangiectasia may have multiple telangiectatic vascular malformations on the skin and conjunctiva, but generally these malformations are absent from the retina and the CNS. The hallmark of the disorder is cerebellar cortical atrophy as well as immunodeficiency.

Summary Table
Condition	Characteristics
Ataxia-telangiectasia	Telangiectasia of skin and conjunctiva, cerebellar ataxia
Sturge-Weber syndrome	Congenital facial angioma, glaucoma, choroidal hemangioma, leptomeningeal hemangioma
Tuberous sclerosis	Astrocytic retinal hamartoma, facial angiofibroma, infantile spasms
von Hippel-Lindau disease	Retinal capillary hemangioma, associated with cerebellar vascular tumors, renal cell carcinoma, and pheochromocytoma
Wyburn-Mason's syndrome	Retinal arteriovenous communications, associated with intracranial arteriovenous malformations

Sturge-Weber syndrome is characterized by a facial port-wine stain, glaucoma, and diffuse choroidal hemangioma, which gives the fundus a "tomato ketchup" appearance. They also may have ipsilateral leptomeningeal hemangiomas.

Tuberous sclerosis is characterized by an adenoma sebaceum rash on the nose, cheeks, and forehead and is associated with infantile spasms and mental retardation. Patients with tuberous sclerosis also may have astrocytic hamartomas, which are small, white masses in the retina and near the optic nerve.

The clinical appearance of Wyburn-Mason's syndrome is different, with direct arteriovenous communications between retinal arteries and veins but no intervening capillary bed. Affected patients may have intracranial arteriovenous malformations.

Address correspondence to Jeffrey L. Olson, M.D., at jeffrey.olson@UCHSC.edu. Reprints are not available from the authors.

Author disclosure: Nothing to disclose.

REFERENCES

1. von Hippel E. Über eine sehr seltene Erkrankung der Netzhaut. Klinische Beobachtungen Archive fur Ophthalmologie 1904;59:83-106.

2. Lindau A. Studien ber Kleinbirncysten Bau. Pathogenese und Beziehungen zur Angiomatosis Rentinae. Acta Radiol et Microbiol Scandinavica Suppl 1926;1:1-128.

3. Seizinger BR, et al. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 1988; 332:268-9.

4. Maher ER, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990;77:1151-63.

5. Othmane IS, et al. Postpartum cerebellar herniation in von Hippel-Lindau syndrome. Am J Ophthalmol 1999;128:387-9.

6. Cohen VM, et al. Choroidal hemangiomas with exudative retinal detachments during pregnancy. Arch Ophthalmol 2002;120:862-4.

7. Hardwig P, et al. Von Hippel-Lindau disease: a familial, often lethal, multi-system phakomatosis. Ophthalmology 1984;91:263-70.

8. Neumann HP, et al. Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus. Lancet 1991;337:1052-4.

9. Girelli R, et al. Pancreatic cystic manifestations in von Hippel-Lindau disease. Int J Pancreatol 1997;22:101-9.

10. Pinkerton OD. Angioma of the retina: report of two cases with fundus photographs. Am J Ophthalmol 1946;29:711.

11. Singh AD, et al. Treatment of retinal capillary hemangioma. Ophthalmology 2002;109:1799-806.

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