Bilateral Striopallidodentate Calcinosis:Report of Two Cases and A Review of the Literature

Bilateral Striopallidodentat Kalsifikasyon:

iki Olgu Sunumu ve Literatiiriin Gozden Ge~irilmesi

BA$AR ATALAY, MURAD BAVBEK, HAKAN CANER, NUR ALTINORS

Ba~kent University Faculty of Medicine, Department of Neurosurgery, Ankara, Turkey

Received: 10.04.2002 c> Accepted: 21.01.2003

Abtract: Objectives: Striopallidodentate calcinosis is arelatively rare pathological condition encountered inneurological practice that presents with a range ofclinical symptoms. Often this lesion is first detected as anincidental finding on radiological examination.Patients and Methods: We report two cases of bilateralstriopallidodentate calcinosis that presented withheadache and paresthesia, and featured similarradiological findings. One patient was a 49-year-oldwoman who had been operated for thyrotoxicosis due toGrave's disease 18 years ago. The other patient was a 62­year-old man who presented with low-back pain. Bothpatients' neurological examination were normal.Results: In both patients, cranial computerizedtomography revealed bilateral diffuse calcifications inthe cerebellum, basal ganglia, thalamus and whitematter. First patient had postoperative hypocalcemia dueto hypoparathyroidism and in the other patient therewere no abnormal findings on blood biochemistrytesting and endocrinologic screeningConclusion: Bilateral intracerebral calcification is usuallydetected as an incidental radiological finding. It isimportant to diagnose the underlying pathology becausemost causes, such as hypoparathyroidism, are treatable.Asymptomatic patients should be followed carefullybecause cerebellar symptoms, parkinsonian symptoms,

Ozet: AmaF Striopallidodentat kalsifikasyonlar degi~ikklinik semptomlarla birlikte olan ve noroloji pratigindenadiren gortilen bir durumdur. Bu lezyonlar genellikleradyolojik incelemeler sonucunda rastlanhsal olarakfarkedilir.

Olgular ve method: Bu yazlda ba~agnsl ve uyu~malarlaba~vuran ve radyolojik bulgulan birbirine c;okbenzeyeniki striopallidodentat kalsinozis vakasl sunulrnu~tur.Birinci vaka 18 sene once Grave's hastahgma baghtirotoksikoz nedeniyle opere edilrni~ 49 ya~mda kadmhastaydl. Diger vaka ise bel agnsl yakmrnaslylaba~vuran 62 ya~mda erkek hastaydl. Her iki hastarunnorolojik muayenesi norrnaldi.Bulgular: Her iki vakarun beyin tomografisinde; beyazcevher, talamus, bazal ganglia ve serebellumda difuzbilateral intrakranial kalsifikasyonlar rnevcuttu. ilk vakahipoparatiroidizrne bagh hipokalserni ile ba~vururkendiger vakamn biyokirnya ve endokrinolojik incelemelerinormal smular ic;erisindeydi.Sonur: Bilateral intrakranial kalsifikasyonlar genelliklerastlanhsal radyolojik bir bulgu olarak goriihir.Hipoparatiroidizm gibi birc;ok etyoloji tedaviedilebildiginden bu vakalann alhnda yatan patolojininiyi ortaya konulmasl gerekir. Serebeller, parkinsonsemptomlar, ekstrapirarnidal ve kognitif bulgularzamanla ortaya C;lkabildiginden asernptornatik vakalarmdikkatlice takip edilrneleri gereklidir.

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Turkish Neurosurgery 13: 67-71, 2003 Atalay: Bilateral 5triopallidodelltate CalcillOsis: Report of Two Cases alld A Rei'iew

and extrapyramidal and cognitive abnormalities maydevelop over time.Key Words: Fahr's disease, hypoparathyroidism,striopallidodentate calcinosis

INTRODUCTION

Deposition of calcium salts in tissues otherthan bone is a pathological process. Necrosis orhyalinization often precedes calcification. Howeverthere are some conditions in which calcium can be

deposited in tissues under physiologicalconditions. Physiological calcification is oftenobserved in arachnoidal granulations and in thebasal ganglia, dentate nuclei, choroid plexus,commissure of habenulae, pineal gland, pituitarygland, ligaments and dura. Examples ofpathological conditions for cerebral calcificationinclude: infection, vascular disease and neoplasiaof the cerebrum. Multiple symmetric macroscopiccalcifications of the basal ganglia are very rare inclinical practice, and they are called "BilateralStriopallidodentate Calcinosis". These are oftenincidental findings that prompt medical attention(15). Extensive symmetric calcification of the basalganglia, cerebellum, cerebral and cerebellar cortices(striato-palido-dentales) is a common finding inpatients with hypoparathyroidism or pseudohy­poparathyroidism (1,5,7-11). Symmetric bilateralintracranial calcifications who have normal

parathyroid glands and normal serum calciumlevels is defined as Fahr's disease (2,4,5,7,13,14,16).In this article, we describe the cases of two patientswith the rare condition striopallidodentatecalcinosis, and also review the relevant literature.

CASE REPORTS

Two patients at our clinic have beendiagnosed with bilateral symmetricalstriopallidodentate calcinosis in the past 2 years.Each individual underwent a thorough work-up,including measurement of serum calcium (Ca)level and assessment of parathyroid function. Bothwere evaluated with computerized tomography(CT).

Case 1: A 49-year-old woman presented withthe complaints of headache and abnormalsensation in her hands. Eighteen years previously,

Anahtar Kelimeler: Fahr hasta!lgl, hipoparatiroidizm,striopallidodentat kalsifikasyon

she had been operated for thyrotoxicosis due toGrave's disease. She has developed hypocalcemiaas a results of the parathyroidectomy for eighteenyears. The patient's blood biochemistry findingswere normal except for hypocalcemia (Ca 7.6mg/dL) and elevated serum phosphorus (P 7.1mg / dL). Cranial CT revealed diffuse calcificationsbilaterally in the cerebellum, thalami, basal gangliaand white matter (Figure 1).

Figure la: Cranial computerized tomography of Case 1with bilateral striopallidodentate calcinosis.This individual had post-parathyroidectomyhypocalcemia. Note the calcifications in thewhite matter, thalami and basal ganglia.

Case 2: A 62-year-old man presented with thecomplaints of low-back pain, headache andabnormal sensation around the lips. Hisneurological examination was unremarkableexcept for paraspinal muscle spasm and perioralhypoesthesia. There were no abnormal findings onblood biochemistry analysis or endocrinologicscreening (Ca 9.8 mg / dL, P 5.06 mg / dL,parathyroid hormone 20.4 pg/ml). Cranial CT

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Turkish Neurosurgery 13: 67-71, 1003 Atalay: Bilateral Striopal/idodentate Calcinosis: Report o/Two Cases and A Review

Figure Ib: Computerized tomography of case 1 patientshows bilateral cerebellar calcifications.

revealed diffuse calcifications bilaterally in thecerebellum, thalami, basal ganglia and whitematter, that was consistent with the diagnosis ofFahr's disease (Figure 2).

Figure 2a: Cranial computerized tomography of Case 2with Fahr's disease. Calcifications are evidentin the white matter, thalami and basalganglia.

Figure 2b: Computerized tomography of case 2demonstrates calcifications in both cerebellarhemispheres.

DISCUSSION

Wider use of new technology is increasing thenumber of cases of macroscopic bilateral basalganglia calcifications that are detected. Manyasymptomatic patients with these lesions areexamined by CT for other medical reasons, and thecalcifications are discovered incidentally. Comilleet al. examined 2318 cerebral CT scans of patientspresented with any neurological symptomsretrospectively during 1993-1995. They found that12.5% of the CT showed calcification of the basal

ganglia, and that the most frequent site ofdeposition noted was the globus pallidus (96.4%).In this retrospective study of 2318 cerebral CT theauthors observed no correlation between the

anatomic sites of calcification and the presentingsymptoms (6).

Multiple microscopic calcifications of thebasal ganglia and hippocampus are commonincidental findings in the brains of elderly people(2,16). In general, cerebral calcium deposits in thisgroup are thought to be due to vascular changesassociated with aging. However, macroscopicbilateral basal ganglia calcifications in any agegroup are usually associated with neurological and

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Turkish Neurosurgery 13: 67-71, 2003 Atalay: Bilateral 5triopallidodentate Calcinosis: Report of Two Cases and A Review

metabolic diseases. These lesions may be seen inpatients with endocrinological diseases, such ashypoparathyroidism or pseudohypoparathy­roidism. Some individuals develop calcificationsafter thyroid or parathyroid surgery. Case 1 is anexample of post-surgical hypoparathyroidism.Removal of the parathyroid glands iatrogenicallyduring thyroid surgery led to brain calcification inthis patient. Serum calcium and phosphorus levelsshould be closely monitored in all individuals whoundergo thyroid or parathyroid surgery, because insome cases, such as parathyroidectomy, it is notpossible to measure parathyroid hormone levels.Kowdley et al. investigated the relationshipbetween intracranial calcification and cognitivedeficits in 11 hypoparathyroid patients (9).Neuropsychological testing revealed impairmentin 65% of this group, and the authors found apositive correlation between the presence ofcognitive deficits and the presence of intracranialcalcifications. Keck et al. reported functionaldisturbances in the brains and cerebella of six

patients who had clinical and biochemical signs ofparathyroid gland malfunction and symmetricalcerebral calcifications (8). We did not observe anycognitive dysfunction in our patient with post­surgical brain calcifications but this is anotherimportant point to consider during further follow­up in this case.

Post-inflammatory brain calcification mayoccur as a sequela of i~fections such astuberculosis, toxoplasmosis, cysticercosis andcongenital human immunodeficiency virus.Bilateral cerebral calcifications may also becongenital, as in tuberous sclerosis, Down'ssyndrome, mitochondrial encephalomyopathies(MELAS / MERRF), Cockayne's syndrome,neurofibromatosis and methemoglobinopathy.Post-anoxic / toxic conditions can also facilitate thistype of bilateral deposition. Examples includecarbon monoxide poisoning, lead intoxication,chemotherapy and radiotherapy.

There are also idiopathic cases in which noendocrine abnormality or any other cause can beidentified. Fahr's disease is an idiopathic familialform of bilateral basal ganglia calcification (2,12).Bamberger was the first to describe bilateral basalganglia calcifications in 1855. Fahr described thefirst adult case of bilateral basal ganglia

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calcification with its clinical and histologicalfindings in 1930. Fahr's disease, which is alsoknown as bilateral striopallidodentate calcinosis ishistopathologically characterized by bilateralextensive calcifications of the globus pallidus,putamen, caudate nucleus, internal capsule,thalamus, and the dentate nucleus of thecerebellum (16).

Plain films of the skull in all types ofintracranial calcifications usually show only thehighly concentrated calcifications. Computedtomography is more sensitive, and thereforedemonstrates even very small quantities ofcalcium. The findings on CT are distinct andconsistent whereas the magnetic resonance imageson Tl- and T2-weighted sequences may vary (15).Interestingly, however, neurological symptoms aremore strongly correlated with the hyperintensitieson T2-weighted images than with calcifications onCT. Hyperintense lesions on T2-weighted imagesmay reflect a slowly progressing metabolic orinflammatory processes that subsequently calcify,causing the neurological deficit (3).

Histologically, in most types of intracranialcalcifications the calcium is deposited along thecapillaries and in the medial walls of larger arteriesand veins (15). Smeyers-Verbeke et al. reported thatcomposition of an intracranial calculus was purehydroxyapatite in a patient with idiopathicintracranial calcifications (14). They found that thecalcification process started with the formation ofsmall round bodies that eventually becamecemented to each other to form the final

macroscopic stone. Researchers who haveinvestigated the pathogenesis of Fahr's diseasespeculate that local circulatory disturbances, suchas regional ischemia, may be the primary triggerfor precipitation of calcium and other minerals (2).

In contrast, Pronica et al. postulated thathypoparathyroidism-like changes due to chronicrespiratory alkalosis cause the bilateralmacroscopic calcifications in patients with Fahr'sdisease (13).

In accordance with rates noted in the literature,

we rarely see cases of macroscopic bilateralintracerebral calcification at our clinic. In the patientswe have diagnosed, the most frequent cause ishypoparathyroidism / pseudohypoparathyroidism,

Turkish Neurosurgery 13: 67-71, 2003 Atalay: Bilateral 5triopallidodelltate Calcillosis: Report o/Two Cases and A Review

and idiopathic cases are next most frequent.Although our two patients exhibited similar CTfindings, the causes of their lesions were different.Hypocalcemia resulting from parathyroidectomywas the etiology in the first case, but even detailedbiochemical and endocrinological investigationsdid not reveal the cause in the second case. As

described previously, patients with calciumdeposits in these locations may develop cognitive,cerebellar or parkinsonian symptoms. It is veryinteresting that such large amounts of calcificationin the eloquent parts of the brain did not causesignificant neurological symptoms in either ofthese individuals. Such patients must be monitoredcarefully in the long term, as they may eventuallydevelop cognitive symptoms. Both neurologicalexaminations and biochemical screening are keyelements of follow-up.

REFERENCES

1. Altmors N, Arda N, Turker A, Senveli E, Kars 2,<;:mar N: Cerrahi hipoparotiroidi'de BBT bulgulan.Noroloji Noro~iriirji Psikiyatri Dergisi 3(2):82-83,1988

2. Ang LC, Rozdilsky B, Alport EC, Tchang S: Fahr'sdisease associated with astrocytic proliferation andastrocytoma. Surg NeuroI39(5):365-9, 1993

3. Avrahami E, Cohn DF, Feibel M, Tadmor R: MRIdemonstration and CT correlation of the brain in

patients with idiopathic intracerebral calcification. JNeuroI241(6):381-4,1994

4. Brodaty H, Mitchell P, Luscombe G, Kwok H,Badenhop RF, McKenzie R, Schofield PR: Familialidiopathic basal ganglia calcification (Fahr's disease)without neurological, cognitive and psychiatricsymptoms is not linked to the IBGC1 locus onchromosome 14q. Hum Genet 110(1):8-14, 2002

5. Forman MB, Sandler Mp, Danziger A, Kalk WJ: Basalganglia calcification in postoperativehypoparathyroism. Clin Endocrinol (Oxf) 12(4):385­90, 1980

6. Gomille T, Meyer RA, Falkai P, Gaebel W,Konigshausen T, Christ F: Prevalence and clinical

significance of computerized tomography verifiedidiopathic calcinosis of the basal ganglia. Radiologe41(2):205-10,2001

7. Idris MN, Sokrab TE: Unusual neuropsychiatricmanifestations of hypoparathyroidism: report of twocases. East Afr Med J 75(2):127-8,1998

8. Keck E, Schuier FJ, Thorner G, Ischebeck W, Durdel

R, Wiegelmann W: Symmetric cerebral calcificationassociated with disturbed parathyroid function. MedKlin 73(43):1507-12,1978

9. Kowdley KV, Coull BM, Orwoll ES: Cognitiveimpairment and intracranial calcification in chronichypoparathyroidism. Am J Med Sci 317(5):273-7,1999

10. Manyam BY;Bhatt MH, Moore WD, DevleschowardAB, Anderson DR, Caine DB: Bilateral

striopallidodentate calcinosis: cerebrospinal fluid,imaging and electrophysiological studies. AnnNeuroI31(4):379-84,1992

11. Mendelsohn DB, Hertzanu Y, Freidman L:

Hypoparathyroidism with cerebral calcificationextending beyond the extrapyramidal system. A casereport. S Afr Med J 65(19):781-2,1984

12. Osborn AG: Inherited metabolic, white matter, and

degenerative diseases of the brain, in Osborn AG(ed), Diagnostic Neuroradiology, St. Louis: Mosby,1994: 716-47

13. Pronica E, Kulczycki J, Rowinska E, Kuran W:Abolished phosphaturic response to parathormonein adult patients with Fahr disease and its restorationafter propranolol administration. J NeuroI235(3):185­7,1988

14. Smeyers-Verbeke J, Michotte Y, Pelsmaeckers J,Lowenthal A, Massart DL, Dekegel D, Karcher D: Thechemical composition of idiopathicnonarteriosclerotic cerebral calcifications. Neurology25(1):48-57, 1975

15. Taveras JM: General pathologic conditions, inTaveras JM (ed), Neuroradiology, third edition,Baltimore: Williams & Wilkins, 1996: 79-106

16. Uygur GA, Liu Y, Hellman RS, Tikofsky RS, CollierBD: Evaluation of regional cerebral blood flow inmassive intracerebral calcifications. J Nucl Med36(4):610-2, 1995

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