Microvasculopathy May Precede Idiopathic Cerebral
Calcifications — Case Report
Camilo R. Gomez, M.D., A.F.A.C.A.
Antonio Luque, M.D., Ph.D.
and
Simon Horenstein, M.D.

ST. LOUIS, MISSOURI

Abstract
Cerebral and cerebellar calcifications were discovered by computerized tomography (CT) in a man who presented with a dementing illness characterized
by progressive memory loss, irritability, and dystonia. He had no known family.
Magnetic resonance imaging showed areas of absent signal corresponding to the
calcifications and areas of high-intensity signal on the T2-weighted images without counterpart on the CT. These are postulated to be static liquid pools secondary to endothelial membrane incompetence and leakage of plasma-derived
fluid.

Introduction

Radiographic changes thought to be representative of &dquo;calcification&dquo; of the basal ganglia
have been associated with many different conditions. These changes have consisted of areas of
hyperdensity that result from the deposition of different minerals, among which calcium seems
to be the principal compone.nt.’ Radiologic evidence of mineral deposition in the basal ganglia
has been correlated with neurologic syndromes, which include different combinations of impaired mental function, dysarthria, dystonia, rigidity, tremor, choreoathetosis, seizures, and
ataxia. Only 1 of these cases has been studied with magnetic resonance imaging (MRI).2 More
recently, other investigators have described the MRI findings in patients with cerebral calcifications associated with other conditions such as acquired immune deficiency syndrome
(AIDS).3 We present the MRI findings of 1 patient who meets the clinical and radiographic
criteria for the diagnosis of what has been previously referred to as &dquo;Fahr’s disease&dquo; (idiopathic calcification of the basal ganglia).
From The Stroke Resource Center, Department of Neurology, St. Louis University Medical Center, and The Department
of Neurology, St. Louis Veterans Administration Medical Center, St. Louis, Missouri

67

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Case Report
The patient is a forty-six-year-old printer who was referred to us because of progressive
deterioration of memory during the five to six years prior to admission. Concomitantly with
the memory disturbance he exhibited increasing dysarthria and irritability. He denied any other
mental or physical problems. He used no calcium-containing compounds and admitted only to
the occasional use of acetaminophen and antacids containing aluminum and magnesium. He
had been adopted and knew nothing of his biological family. He had been employed as an
offset printer for twenty-four years but without industrial exposure to toxins, chemicals, or
metals.
His height was 1.82 m, and he weighed 57.2 kg. A II/VI systolic ejection murmur heard
best at the cardiac apex radiated to the left sternal border. He was awake, alert, well oriented,
and cooperative but became easily frustrated whenever he was unable to complete tasks during
the examination. His speech was dysarthric with special difficulty forming voiced consonants.
Language function was otherwise normal. Registration, storage, and recall of both recent and
remote events were decreased, and his Wechsler memory quotient was 81. His attention span,
as measured by digit retention, was decreased (4 forward, 4 backward with 7 and 6 expected
respectively). Judgment was rather concrete (an apple and an orange were similar in that &dquo;both
were round&dquo; and his interpretation of proverbs laced abstraction). Wechsler Adult Intelligence
Scale (WAIS) score was 87 (verbal performance). He did poorest in tasks requiring memorization. The optic fundi were normal. Despite normal posture and normal strength, tone, coordination, and bulk of all his muscles, there was dystonia of the right upper and lower limbs.
The former was held in pronation and not swung fully upon walking. The latter became
immobile during the swing phase of walking, often causing him to trip. Sensation and coordination were normal. He nimbly executed purposive movements. Muscle stretch and cutaneous
reflexes were normally active and symmetrical. The plantar responses were flexor bilaterally.
Values for hematology, serum chemistry, serology, thyroid function tests, vitamin B12 levels, and folate levels were in the normal (N) range. Free serum calcium was 4.8 mg/dL
(N=4.5-5.0), and serum ceruloplasmin was 37 mg/100 mL (N=27-338). Parathyroid hormone level was 6 mL Eq/mL (N= < 3-10). Radiologic studies of kidney, abdomen, limbs, and
spine disclosed no other ectopic calcifications.
=

Methods
The patient underwent cranial computerized tomography (CT) with a third-generation
high-resolution scanner and, later, MRI with a 0.15 Tesla resistive magnet. The magnetic
images were obtained with spin-echo (SE) recovery sequences of echo (TE) and repetition
times (TR) of 30 and 1030 msec, respectively, and later with TE
120 msec and TR
2120
msec. The first set yielded proton-density images and the second, T2
weighted images.
=

=

=

Results
The CT images showed areas of increased attenuation localized in the basal ganglia, cerebellar nuclei, and white matter of the cerebral hemispheres (Figure 1). MR images revealed
areas of decreased signal on both proton density and T2-weighted images (Figures 2 and 3).

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69
These corresponded to the regions of calcification seen on CT. Additionally, areas of increased
signal were present in the white matter of the cerebral and cerebellar hemispheres. These were
adjacent to but not within the regions of calcification.
Discussion

Before the use of computerized tomography (CT), two thirds of the cases of cerebral
calcifications were thought to be secondary to abnormalities of calcium metabolism , most
commonly, pseudohypoparathyroidism. Since the introduction of CT, however, it has been
possible to find areas of increased radiodensity in the basal ganglia of 0.33-1.5 % of all cranial
examinations.5 Some of these cases have been found to occur in families,6-9 and the incidence of
abnormalities of calcium metabolism among all these patients varies altogether from 0-5 % .
Although the name of Fahr has been linked to the familial form of the disorder, this is probably
not justified since the patient reported by Fahr’° had no history suggestive of a familial tendency. Additionally, almost a century earlier, Delacour had already recognized and described
this entity.&dquo;
Pathologically, the process responsible for mineral deposition in the basal ganglia, cerebral
hemispheres, and cerebellum has been a matter of controversy. Some have believed it to

FIG. 1. CT images show extensive areas of increased attenuation on
the basal ganglia, cerebellar nuclei,
and cerebral white matter.

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70

represent the deposition of iron and calcium in the walls of the arterioles and venules of the
cerebral white matter and nearby deep gray nuclei.3,4,6 Extensive postmortem studies of the
cerebral calcifications of 1 patient led several investigators to conclude that these were due to a
process similar to natural calcification and that, although the capillaries were involved this was
only a secondary change.’2 The fact that ferrugination is also prominent has led others to
postulate that the accumulation of iron and calcium occurs in response to the extravascular
deposition of an acid mucopolysaccharide-alkalic protein complex. Other minerals that have
been found in different concentrations in such deposits are copper, aluminum, zinc, cobalt,
manganese, magnesium, lead, arsenic, and other trace elements.’2 Whether mineral depositions in the brain are only part of a more generalized process that may also cause mineralization of other parts of the body (such as in the case of Wilson’s disease) is unknown at present.
No studies of other organs have been reported.
Several theories have been proposed to explain the mechanism of formation of these areas
of ferrugination and calcification in the brain. None of them has, however, been proved.
Among the explanations offered, previous cerebral anoxia&dquo; and vascular disturbances in arterial &dquo;boundary zones&dquo;’4 are the best known. Increased tissue &dquo;avidity&dquo; for the deposited
mineral, as has been postulated in Wilson’s disease,&dquo; is also a possibility. The concept of some

FIG. 2.

Proton-density MR im-

ages show areas of decreased signal
(solid arrows) which correspond to
the areas of increased attenuation on
CT.

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71
form of microvascular insufficiency being responsible for this abnormal mineralization is a
very interesting one since the deposits follow the course of the blood vessels. The results from
the recent study of Belman et al3 demonstrate that the penetrating vessels of the basal ganglia
are primarily involved by the calcific process. They have suggested that a vasculopathy may be
the factor that eventually ends in calcification of the neuropil.
Conclusions
The presence of high-intensity signal on MRI with T2-weighted SE sequences and lowintensity signal on proton-density SE sequences is suggestive of high liquid content (long T1
and T2) such as is seen in edematous states. 14-16 These areas appear distinct from the areas of
mineral deposition, which have increased attenuation of CT and long T and short T2 on MRI.
Perhaps these regions of edematous appearance represent the stage that precedes mineralization. Vascular membrane abnormalities may be responsible for the leakage of plasma-derived
fluid, and this, in turn, may damage the neuropil and result in mineral accumulation. Further
study of patients with cerebral mineralization using gadolinium-DTPA (diethylenetriaminepentacetic acid) -enhanced MRI may be helpful in demonstrating abnormalities of the blood-brain
barrier. In addition, since the edematous areas may be seen prior to mineral deposition, such a

FIG. 3. T2-weighted MR images
show areas of decreased signal inten-

sity (solid arrows) corresponding to
the areas seen in previous images and
periventricular areas of increased signal (open arrows) representing &dquo;edematous&dquo; tissue.

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72

finding may be useful in screening members of affected families.
Acknowledgment
The authors wish to thank Mrs. Mary Althage for her secretarial assistance in the preparation of the manuscript.
Camilo R. Gomez, M.D., A. F. A. C. A.
The Stroke Resource Center

Department of Neurology
St. Louis University Medical Center
3660 Vista, #305
St. Louis, MO 63110

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