62ournal ofNeurology, Neurosurgery, and Psychiatry 1993;56:622-625

A prospective study of patients with CT detectedpallidal calcifications

G Fenelon, F Gray, F Paillard, M Thibierge, F Mahieux, A Guillard

AbstractIn a prospective study pallidal calcifica-tion was detected in 30 of 1478 (2%) adultpatients, on CT brain scans. In 8 cases(26%), the calcifications were detectedeither years after, or during the courseof, conditions known to cause basalganglia calcification, including AIDS infour cases. Eight patients (three withAIDS) had disturbances of calcium andphosphorus metabolism. It was con-cluded that: a) pallidal calcification isnot uncommon and aetiological factorsmay be recognised more often thanpreviously reported; b) AIDS is emergingas a significant cause of pallidal cal-cification in young adults, and c) inAIDS and other conditions, abnormalcalcium and phosphate metabolism mayact in conjunction with local vascularchanges.

(T Neurol Neurosurg Psychiatry 1993;56:622-625)

Service des maladiesdu systeme nerveux,Hopital Tenon, Paris,FranceG FenelonF MahieuxA GuillardDepartment depathologie(neuropathologie),Hopital HenriMondor, CreteilF GrayService d'explorationsfonctionnelles,Hopital Tenon, ParisF PaillardService de radiologie,Hopital Tenon, ParisFranceM ThibiergeCorrespondence to:Dr Fenelon, Service desmaladies du systemenerveux, H6pital Tenon, 4rue de la Chine, 75020Paris, France.Received 13 January 1992and in revised form1 April 1992.Accepted 16 July 1992

With the increased availability of CT, theincidental discovery of pallidal calcificationshas become more frequent. The significanceof such calcifications is unclear, but some

authors claim that those confined to thepallidum should be considered as "physio-logical" in subjects over the age of 40 years.1However, the list of conditions associatedwith basal ganglia calcifications, whetherlimited to the pallidum or not, is expanding.The aim of this prospective study was toassess the prevalence and clinical significanceof pallidal calcification in a population ofpatients in our hospital having CT.

Patients and methodsAll inpatients and outpatients who had CT ofthe brain during a 16 month period were

included in this study.CT was performed using either a CGR CE

10 000 or a Siemens Somatom Dr. All scans

were assessed by the same neuroradiologist(MT). Hyperdensity of pallidal areas was

identified visually and measured.All patients with CT detected pallidal cal-

cifications were interviewed and examined byone of us (GF); the records were reviewedwith the patients' informed consent. Certainconditions (past or present) were systemati-cally investigated, that is, endocrine andmetabolic diseases, exposure to toxic sub-

stances (including lead), carbon monoxidepoisoning, anoxia, CNS infection and cranialirradiation. Long term treatments and familyhistories were also recorded.

Serum levels of calcium and phosphoruswere measured at least twice. Abnormal levelsprompted further investigations, includingcalcium and phosphate excretion, parathor-mone (PTH) levels (radio-immunologicalassay), nephrogenic cyclic AMP (that iscAMP secreted by the tubule under the influ-ence of PTH), and another index of PTHactivity, the renal threshold phosphate con-centration.

Post mortem examination, performed intwo cases (6 and 15), was restricted to thebrain. Gross examinations were made oncoronal sections of the cerebral hemispheresand on sections of the cerebellum and thebrainstem perpendicular to its axis. Tissueblocks were embedded in paraffin wax.Thick slices of each cerebral hemisphere andthe cerebellum/brainstem were embedded incelloidin. Sections were stained with haema-toxylin and eosin, the Loyez method formyelin, Bodian silver impregnation com-bined with Luxol fast blue, periodic acidSchiff (PAS), Perl's method (Prussian blue)for iron and the Von Kossa method for cal-cium. Paraffin sections were immunostainedfor HIV detection using an indirect methodwith immunoalkaline phosphatase andmonoclonal antibodies against p24 and p17(DuPont).

ResultsThirty patients (2.03%) with pallidal calcifi-cations were identified among 1478 patientswho had CT of the brain. There were 20women and 10 men, with a mean age of 60O3years (range: 31-90). Only seven of the thirtypatients were under fifty years of age. Nonehad clinical features indicating basal gangliadysfunction, such as a Parkinsonian syn-drome or dyskinesias of any type. The indica-tions for CT varied greatly, the most frequent(n = 7) being a suspicion of cerebralischaemia. The pallidal calcification wasdetected incidentally in all cases. It was bilat-eral in 25 cases and unilateral in 5; there wasassociated calcification of the head of thecaudate nucleus in two instances, and thedentate nucleus in one case. Skull radio-graphs, obtained in 26 cases, showed calcifi-cation in only one.A condition (past or present) known to be

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A prospective study ofpatients with CT detected pallidal calcifications

Table 1 Cases with a possible cause for the basal ganglia calcifications or disturbances in phosphonrs/calcium metabolism

Case Sex, Indication Phospho-cacic metabolism Possible causeforNumbers age for CT Associated conditions disturbance calcifications

1 F, 61 Diplopia Breast cancer Cancer associated hypercalcaemia -2 F, 66 Headache, depression - Carbon monoxide

intoxication(at age 36)

3 F, 69 Suspicion of neoplasia Renal failure, hypertension, Secondary hyperparathyroidism -Search for metastases diabetes

5 F, 86 Internuclear Hypertension, diabetes, ischaemic stroke, Primary hyperparathyroidism Primary hyper PTHophthalmoplegia parathyroid adenoma (known for 6 years)

6 M, 41 Behavioural AIDS, glomerulosclerosis with renal Secondary hyperparathyroidism AIDSdisturbances failure, mild intellectual

impairment7 M, 34 Fever AIDS, pneumocystis carinii pneumonia Isolated hyperphosphatemia AIDS

(metabolic investigationincomplete)

8 F, 64 Seizures Tuberculous meningitiscoma (at age 35)

12 F, 76 Transient ischaemic Ischaemic stroke, osteoporosis, intermittent Hypercalcaemia withattacks treatment with calcium, phosphorus hypercalciuria

and calcitonin15 M, 36 Cerebral toxoplasmosis AIDS, pulmonary tuberculosis, Pseudohypoparathyroidism or AIDS

(follow up) toxoplasmosis of the brain, progressive mild hypoparathyroidismmultifocal leukoencephalopathy

20 M, 55 Intellectual impairment - Tuberculous meningitis(at age 36)

29 M, 31 Cerebral toxoplasmosis AIDS, toxoplasmosis of the brain, Secondary hyperparathyroidism AIDS(follow up) intellectual impairment, renal

failure

Figure 1 CT scans without contrast injection in two patients with AIDS; A) Patient 15(36year old man). Calcifications are small, confined to the pallidal area, bilateral andsymmetrical (the hypodense areas in the left hemisphere are due to toxoplasmosis abscess);B) Patient 29 (31 year man). Bilateral and asymmetrical calcifications involving thebasal ganglia and the right thalamus. Calcifications were detected in the follow up oftreatmentfor cerebral toxoplasmosis.

occasionally associated with basal ganglia cal-cifications was found in eight cases (table 1).The patient with primary hyperparathy-roidism (case 5) had had a parathyroid ade-noma for 7 years but had persistentlydeclined surgical treatment. Four patients (6,7, 15, 29) had the acquired immuno-deficiency syndrome (AIDS) (table 1). Thecalcifications were symmetrical and confinedto the pallidal area in three cases (fig 1A). Inanother patient (29), the calcifications wereasymmetrical and diffuse, extending into boththe lenticular and caudate nuclei, the rightthalamus and the hemispheric white matter(fig IB). These calcifications developedwithin a few months while the patient wasbeing treated for multiple brain abcesses dueto toxoplasmosis.

Three patients could not be investigatedaccording to the protocol: one left the area(case 7), one died shortly after CT (case 19)and one declined further investigation (case27). A disturbance of phosphate/calciummetabolism was found in eight cases (table 1)which included the four patients with AIDS.Two patients (6 and 29) had renal failurewith secondary hyperparathyroidism; one(case 7) had an elevated serum phosphatelevel but could not be investigated further; inthe last case (15), we could not distinguishbetween mild hypoparathyroidism andpseudohypoparathyroidism on the basis of theavailable data.

Neuropathological investigation of twoAIDS patients revealed similar changes. Themineral deposits mainly involved the vesselwalls, consisting either of extensive miner-alisation of thickened arteriolar walls, or ofsmaller globular deposits around capillaries.These deposits appeared dark purple insections stained with haematoxylin and eosin,were PAS-positive, and also stained positivelyfor iron (Perl's method) and calcium (vonKossa's method). Vascular mineralisation wasbilateral and symmetrical, and predominantlyinvolved the basal ganglia, especially the

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~~~~~~~~~~~~~~~~~~~~~Fbilon,Gray, Paillard, 7hiibierge, MahieuX, Guillard

1ii~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.. ............ ...

Figure 2 Pathological changes in two cases with AIDS; A) Patient 15. Globus pallidiDark mineral deposits can be seen in an arteriolar wall and along the capillaries. Note i

presence oflarge inclusion-beating oligodentrocytes characteristic ofPML (at-rows). H6x 1 00; B) Patient 6. Globus pallidus. Minerahsation of vessel walk and ofa focal nec?lesion (arrow). H&E, x 40.

globus pallidus (fig 2A). Alineralisation v

also abundant in the dentate nuclei andvpresent, but to a much lesser extent, incerebral white matter. In the basal gangvascular mineralisation was associated w

mild parenchymal changes includ,1widening of the perivascular spaces wh-contained occasional lipid- or haemosiderladen macrophages, and a few necrotic ftIn case 6, mineral deposits were observedthese necrotic lesions (fig 2B).

In case 15, neuropathological examinat.also showed limited scar lesions due to to:

plasmosis and confirined severe chanjcharacteristic of progressive multifocal leuiencephalopathy mainly involving the heispheric white matter, and also extendingthe basal ganglia (fig 2A). A few multinucated giant cells with cytoplasmic HIV ar

gens were present. In case 6, minirnon-specific changes (including granuependymitis and slight myelin pallor of

624

hemispheric white matter) were associatedwith reactive astrocytosis and microglial pro-liferation. Multinucleated giant cells were

present but immunostaining for HIV was

ne ative.

i8

DiscussionBasal ganglia calcification was found in 2% of1478 patients who had CT of the brain dur-ing the study period. This prevalence ishigher than in previous studies, in which it

%2 to %3ranged from 0-24 1-64 but was gen-erally below 1 %.I" This discrepancy was notrelated to the age of the populations, but mayhave been due to differences in the sensitivityof the CT apparatus used for the study, or toother differences in the populations studied.

Although BGC has been related to manypathological conditions (table 2), severalstudies led to the conclusion that incidentallydetected BGC has no clinical significance. 1 3 4

O' A surprising finding in our series was the highrate of ossible causative or predisposing fac-tors for BGC. However, such results shouldbe interpreted cautiously since, in most

...A.: mstances a definite causal relationship can-not be demonstrated. For example, it is diffi-cult to determine the influence of carbonmonoxide poisoning (case 2) which occuffed30 years before the pallidal calcifications werediscovered. However carbon monoxide poi-soning is a well-established cause of pallidalvascular calcifications.9 AIDS appears to bean emerging cause of BGC in young adults.CT detected BGC was first reported ininfants and children in this setting,10 andrarely in adults." Interestingly, no calcifica-tion was reported in large-scale neuroradio-logical studies of adults with AIDS. 12

!US.However, vascular calcifications in the basal

the ganglia have been described in neuropatho-_.,E, logical studies. 1314 'Me pathogenesis of vascu-rodc lar minerahsation in AIDS is unclear.

Mineralisation of vessel walls as a sequel ofvasculitis with immune complex deposition inthe early stages of HIV infection has beensu ested in both children'O and adults. 15

was This mechanism could account for the sym-was metrical pallidal calcifications of three of our

the four AIDS cases (fig 2A). In another case

aia, (29), the pattem of calcifications was clearly7ith different (fig 2B): they were asymmetrical,ling involved areas other than basal ganglia, andLich developed within treated toxoplasmic lesions.rin- Another surprising finding was the highDCi. prevalence of disturbances in phosphate/cal-in cium metabolism (8/28 patients). Similar

ionxo- Table 2 Main con&tions associated with symmenicalges

basal ganglia calcifications in adulthood

co- Primary and postoperative hypoparathyroidism"Pseudo hypoparathyroidism20Hyperparathyroidism17

to Carbon monoidde poisonineCNS infections, 18 incluchng AIDS 14

Ae- Down's syndrome21

nti- Systemic lupus erythematoSUS22mal Mitochondfial cytopadW3

Chronic lead exposure"Ilar Radiation therapy5the Famflial idiopathic cerebral calcificationS25

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A prospective study ofpatients with CT detected pallidal calcifications

results have been reported in only two otherstudies216 and were related to hypoparathy-roidism. In our study, these abnormalitiessuggested hypoparathyroidism in only onecase. Their direct responsibility in the onsetof BGC is doubtful, except in the case of pri-mary hyperparathyroidism."7 The four AIDSpatients in our study also had abnormalserum phosphate and/or calcium levels. Twohad hyperparathyroidism secondary to renalfailure, a condition not known to cause BGC.It is possible, however, that these abnormali-ties acted as cofactors with local inflamma-tory changes. Such a mechanism (that is theconcurrence of systemic and local factors) hasbeen suggested by Morgante et al.'8 More-over, in a study by Muenter and Whisnant,'9three patients had hypoparathyroidism and a

history of anoxia or encephalitis.In conclusion, whatever the age of the

patient, CT-detected pallidal calcificationsshould not be considered as "physiological"before a thorough clinical investigation andcalcium/phosphate levels are shown to benormal. AIDS is a recently identified cause ofBGC and should be borne in mind, particu-larly in cases involving young adults.

We thank Mrs Line Bazeille and Gisele Corcket for technicalassistance and Mrs Sonia Ceva for preparing the manuscript.

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