Case Report

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A 63-year-old man with a history of hypertension, alcohol abuse, and renal failure (for which he received maintenance hemodialysis) was admitted after having left-sided weakness and slurred speech for 1 day. He recalled having a brief episode of numbness on the left side 1 week earlier. At the initial examination, he was lethargic and had severe dysarthria, left hemiplegia with hyper-reflexia, and left-sided sensory deficits. A head CT scan showed no lesions. Medications before admission included colchicine, 0.6 mg daily; epoetin alfa, 4000 U daily; calcitriol, 0.5 µg twice a day; aluminum hydroxide tablets four times a day; and transdermal nitroglycerin. Laboratory findings at admission were as follows: urea nitrogen, 21.0 mmol/L (60 mg/dL); creatinine, 1040 µmol/L (11.8 mg/dL); calcium, 2.54 mmol/L (10.2 mg/dL); and phosphate, 2.05 mmol/L (6.4 mg/dL). All medications were continued except aluminum hydroxide.

The patient was transferred to our institution for rehabilitation 6 weeks after the stroke. At that time, he was abulic but able to follow one-step commands. At examination, he had moderate dysarthria, slightly improved left-sided weakness, and left-sided sensory neglect. He reported diffuse pruritus. A repeated CT scan Figure 1 6 weeks after the first study showed extensive calcification of the right frontal lobe in the anterior and middle cerebral artery territories. There was no mass effect, and the calcification involved both white and gray matter. Noninvasive studies of the carotid arteries showed a high-grade stenosis at the origin of the right internal carotid artery. Echocardiographic evaluation showed mitral and aortic valve thickening, mitral annular calcification, and a normal ejection fraction. A chest radiograph showed mild cardiomegaly, but no calcific deposits were seen in either the lungs or heart. The electrocardiogram was unremarkable. Laboratory findings at that time were as follows: urea nitrogen, 32 mmol/L (90 mg/dL); creatinine, 1580 µmol/L (17.9 mg/dL); calcium, 2.62 mmol/L (10.5 mg/dL); and phosphate, 3.70 mmol/L (11.5 mg/dL).

View larger version (156K): [in this window] [in a new window]   Figure 1. Brain computed tomographic scan showing extensive calcification of the right frontal lobe in the anterior and middle cerebral artery territories.

Therapy with aluminum hydroxide was restarted, with a subsequent reduction of the serum phosphorus level. Three months after the stroke, the patient was still abulic and dysarthric but had regained enough strength in the leg to walk short distances with a quadripod cane. He was discharged but required 24-hour assistance from his family in activities of daily living.

Discussion

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Metastatic calcification is an uncommon but potentially serious problem in patients with uremia when the cross-product of calcium and phosphate exceeds 4.8 to 6.0 mmol/L [7-9]. In our patient, hyperphosphatemia occurred after therapy with phosphate-binding antacids was inadvertently discontinued. Metastatic deposits of hydroxyapatite can occur in the eye, periarticular soft tissue, and skin, whereas deposition of amorphous or microcrystalline calcium, magnesium, and phosphorus compounds occur in the viscera [8]. The heart and lungs are common sites of visceral calcification, and calcification of these organs can be associated with low-output cardiac failure and restrictive lung disease [9]. Calcification can occur in small-and medium-sized arteries, particularly those in the hands, and can lead, although rarely, to vascular insufficiency and digital gangrene.

The CT scan has a high sensitivity for detecting calcium deposits in the brain [1, 2]. Small, focal calcifications have been associated with vascular malformations (arteriovenous malformation, cavernous angioma), aneurysms, brain tumors, and infections (for example, toxoplasmosis and cytomegalovirus infection). Mineralization primarily restricted to the basal ganglia has been associated with a number of conditions: parathyroid disorders (hypoparathyroidism, pseudohypoparathyroidism), Fahr disease, idiopathic familial basal ganglionic calcification, MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like syndromes), Hallervorden-Spatz disease, and anoxic brain injury [1, 3, 4]. In patients with uremia, the brain content of calcium is increased [10], but brain calcification is a rare finding. Swartz and colleagues [3] described two patients with renal failure and secondary hyperparathyroidism who had basal ganglia and diffuse subcortical calcifications. One patient had encephalopathy that was thought to be secondary to uremia, and the other patient was neurologically normal.

Cortical and white matter calcification is rarely seen after ischemic stroke [2, 5]. In one reported case, a CT scan showed parenchymal calcification 4 months after acute stroke [5]; however, most calcifications are typically discovered years after the event. Small calcium deposits are more commonly seen as the residua of intracerebral hematomas [6]. Our patient had a large ischemic stroke secondary to carotid disease, with extensive dystrophic calcification occurring in a relatively short time. We postulate that, unlike in most patients with stroke, our patient's elevated calcium-phosphate cross-product probably accelerated and exaggerated the process of calcification in the presence of a disrupted blood-brain barrier. We do not know whether hemorrhagic transformation of the infarction occurred between the first and second CT scans and whether such transformation could also have played a role in the process. Despite the dramatic findings on CT scan, there was no attributable neurological deterioration, suggesting that calcium deposition occurred only in areas of infarction.