Pseudoxanthoma Elasticum: A Review of Neurological Complications A l e e m Iqbal, MD, Milton Alter, M D , P h D , a n d S e u n g h o H. Lee, MD ~

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A case of pseudoxanthoma elasticum w i t h multisystem involvement is described. Neurological complications, as reported i n t h e literature, are reviewed. T h e s e include cerebrovascular insufficiency, multiple lacunar infarcts, aneurysms, subarachnoid and intracerebral hemorrhages, progressive intellectual deterioration, and psychic and mental disturbance which may be due to cortical atrophy. Seizures occur m o r e frequently than in the general population. Hypertension and alteration of cerebral vessels are the two basic pathophysiological mechanisms responsible for t h e neurological complications of this disease. Iqbal A, Alter M, Lee SH: Pseudoxanthoma elasticum: a review of neurological complications. Ann Neurol 4: 18-20, I978 P s e u d o x a n t h o m a elasticum (PXE) is a rare hereditary disorder with peculiar loosening of the skin. However, multiple systems including the n e r v o u s system may also be affected. Complications of h y p e r t e n s i o n and cardiovascular disease are t h e m o s t c o m m o n causes of neurological deficits. Aneurysmal dilatation of vessels [ 3 , 5 , 101, subarachnoid and intracerebral

A 54-year-old white woman was admitted to Temple University Hospital because of urinary incontinence and inability to walk for about six months prior to admission. She appeared well nourished and normally developed. H e r blood pressure was 190/100 mm Hg in both right and left arms. The pulse was 72 beats per minute, regular, and equal in radial, femoral, carotid, and temporal regions bilaterally. There were multiple soft, chamoislike, yellowish plaques with prominent creases over the skin of the neck, axillae, and groin (Fig 1). The patient was alert and oriented to person and place but not to time. She was unable to give an adequate history nor could she perform any meaningful cognitive functions. She had an inappropriate affect with bursts of laughter and crying. Visual acuity appeared low. Funduscopy showed disciform degeneration with pigmentation of macula, compatible with the end-stage process of PXE (Fig 2). The cranial nerves were otherwise unremark-

able. She moved all four extremities but had inconsistent weakness of the left side. There were bilateral brisk reflexes with extensor toe responses to plantar stimulation. Sucking, snout, and grasp reflexes were present. From early childhood the patient was considered a spoiled, stubborn child. She did poorly at school and left in the third grade. At 16 years of age she started to work as a carpet weaver but was always considered a “slow worker.“ At age 17 she developed progressive loosening of the skin of her neck, axillae, and groin. She had to stop working at age 35 because of progressive deterioration of vision. In 1962, an ophthalmologist noticed angioid streaks in her fundi. During the next 15 years she was treated for hypertension, failing vision, gastrointestinal bleeding, uterine bleeding, and strokes involving both anterior and posterior circulations. I n 1974 she fractured her ankle and had considerable difficulty in walking thereafter. She became progressively incoherent and deteriorated mentally. She had been bedridden with bladder incontinence for six months prior to her last admission. O n e sibling died in infancy of unknown cause. The patient had 2 brothers and 5 sisters, all of whom had hypertension. O n e brother with similar skin changes died of a heart attack. O n e sister had multiple strokes and inappropriate affect with diminishing vision prior to her death. H e r mother died of cerebral hemorrhage. About three weeks after admission the patient developed left homonymous hemianopia with gaze fixation to the right. The left arm was weak, and she had brisker deep tendon reflexes o n the left side and bilateral extensor toe signs. The EEG demonstrated frequent medium-voltage 2 to 4 and 5 to 7 Hz activity bilaterally, predominantly over the right hemisphere. Frequent sharp waves were observed. T h e radiological examination revealed a normal skull with calcification of the pineal gland, tracheal calcification, ex-

From the Departments of Neurology and Radiology, Temple University Hospital, Philadelphia, PA.

Address reprint requests to Dr Iqbal, Department of Neurology, Temple University Hospital, Philadelphia, PA 19140.

hemorrhages [ 3 , 5,6], bilateral carotid occlusion with bilateral collateral circulation t h r o u g h the mirabile and carotid cavernous fistula, cerebral infarctions, and multilacunar state [7] have been reported. In addition, cortical atrophy and d e m e n t i a , psychoneurotic disorders [ l , 2, 4 , 8, 9, 111, and focal or generalized seizures with and w i t h o u t electroencephalographic changes [2, 4 , 5, 111 have been described.

Case Report

Accepted for publication Jan 6, 1978.

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0364-5~34/7810004-0103$01.25@ 1978 by Aleem Iqbal

F i g 2. Fundus J-hozus di.iciform degeneration (arrowheads),the

end-stage o f P X E .

Fig 1. Neck andaxilla demonstrate prominent creases ovey the skin, with plaque.i (arrows) spread through them.

tensive abdominal aortic calcification, and diffuse arterial Calcification of upper and lower extremities. Serial com-

puted tomography demonstrated moderate enlargement of the ventricular system and slight cortical atrophy. A complete blood count and serum electrolytes, including calcium and phosphorus, were normal. Blood sugar ranged from 86 to 146 mg per deciliter o n different tests. Twohour postprandial glucose was 162, 128, and 100 mg per deciliter, respectively, o n three different occasions. Serological tests were negative. There was no evidence for collagen vascular diseases. A skin biopsy demonstrated a marked increase in branching, fragmentation, and calcification of elastic fibers in the dermis, characteristic of PXE.

Discussion PXE is usually an autosomal recessive disorder with increased parental consanguinity [6] and a high incidence of affected siblings. However, autosomal dominant and sporadic cases without any familial predilection [ 8 ] have been reported. There appears to be no racial preponderance. Abnormalities of the blood vessels are common and account for many of the serious complications of the disease. T h e widespread calcification of the aorta

[7] and peripheral arteries, as present in our patient, had been shown in the choroid plexus and in carotid artery aneurysms bilaterally [ 101. Symptoms associated with vascular disease may be absent o r severe depending upon the location of the affected vessel and the degree of its involvement. T h e patient may complain of paresthesia, numbness, or intermittent claudication. Aneurysms often involve the cerebral arteries with secondary complications [3, 5 , 101. Subarachnoid hemorrhage has been a major cause of death [6]. Availability of C A T scanning offers an opportunity to assess the presence of cortical atrophy and ventricular dilatation early in the course. Frequent association of prominent mental or psychiatric disturbances such as forgetfulness or impaired memory, dull mentality, depression [ 11, psychoneurosis [9], and mental deterioration [ 111all have been described in association with PXE. Changes in the eyes in PXE consist of angioid streaks of the fundus due to ruptures in Bruck’s membrane of the choroid which occur o n the basis of degeneration of elastic fibers in the elastic lamina. In later stages, the streaks are broadened by pigmentary migration which surrounds the disc and radiates toward the periphery. Retinal hemorrhages are seen frequently in the angioid streaks. Macular involvement or hemorrhages from the choriocapillaris may impair central vision. No specific EEG abnormality has been reported [ 111, but the incidence of seizures is increased [Z].

Iqbal, Alter, and Lee: Neurological Complications of Pseudoxanthoma Elasticum

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References

6. McKusick VA: Heritable Disorders of Connective Tissue. St

1. Carlborg U, Ejrup B, Gronblad E, et al: Vascular studies in pseudoxanthoma elasticum and angioid streaks. Acta Med Scand 166:Suppl 35O:l-84, 1959 2. Conner PJ, Juergens JL, Perry HO, et al: Pseudoxanthoma elasticum and angioid streaks: a review of 106 cases. Am J Med 30:537-543, 1961 3. Dixon JM: Angioid streaks and pseudoxanthoma elasticum with aneurysm of internal carotid artery. Am J Ophthalmol 34:1322-1323, 1951 4. Eddy DD, Farber EM: Pseudoxanthoma elasticum internal manifestations: a report of cases and a statistical review of the literature. Arch Dermatol 86:729-740, 1962 5. Goto K: Involvement of central nervous system in pseudoxanthoma elasticum. Fol Psychiatr Neurol 29:263-277, 1975

20 Annals of Neurology

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No 1 July 1978

Louis, The CV Mosby Company, 1966, pp 286-322 7. Messis CP, Budzilovich GN: Pseudoxanthoma elasticum: report of an autopsied case with cerebral involvement. Neurology (Minneap) 20:703-709, 1970 8. Robertson MG, Schroeder JS: Pseudoxanthoma elasticumsystemic disorder. Am J Med 27:433-442, 1959 9. Scheie H G , Freeman NE: Vascular diseases associated with angioid streaks of retina and pseudoxanthoma elasticum. Arch Ophthalmol 35241-250, 1946 10. Scheie HG, Hogan TF: Angioid streaks and generalized arterial diseases. AMA Arch Ophthalmol 57:855-868, 1957 11. Suerig KL, Siefert FE: Pseudoxanthoma elasticum and sickle cell anemia. Arch Intern Med 113:185-193, 1964

Pseudoxanthoma elasticum: a review of neurological complications.

Pseudoxanthoma Elasticum: A Review of Neurological Complications A l e e m Iqbal, MD, Milton Alter, M D , P h D , a n d S e u n g h o H. Lee, MD ~ ~...
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