Journal of Neuro-Ophthalmology, March 1994, Volume 14, Issue 1

Idiopathic striopallidodentate calcification with prominent supranuclear abnormality of eye movement.

We present a 63-year-old man with idiopathic striopallidodentate calcifications who exhibited a marked supranuclear defect of eye movement in addition to an extrapyramidal movement disturbance and dementia. The resulting clinical disorder resembled progressive supranuclear palsy.

journal of Neuro- Ophthalmology 14( 1): 29- 33, 2994. © 1994 Raven Press, Ltd., New York Idiopathic Striopallidodentate Calcification with Prominent Supranuclear Abnormality of Eye Movement Jeffrey L. Saver, M. D., Grant T. Liu, M. D., and Michael E. Charness, M. D. We present a 63- year- old man with idiopathic striopalli­dodentate calcifications who exhibited a marked supra­nuclear defect of eye movement in addition to an ex­trapyramidal movement disturbance and dementia. The resulting clinical disorder resembled progressive supra­nuclear palsy. Key Words: Eye movements- Saccades- Fahr's dis­ease- Basal ganglia calcinosis- Progressive supranu­clear palsy. Idiopathic calcification of the basal ganglia has been associated with a syndrome of progressive movement disorder and neuropsychiatric abnor­mality beginning in mid to late adulthood ( 1). Dys­arthria and extrapyramidal features, including choreoathetosis and parkinsonism, are prominent motor manifestations, and occasional patients ex­hibit pyramidal signs or cerebellar ataxia ( 2). Sei­zures are a rare feature. The condition occurs in sporadic, autosomal dominant and autosomal re­cessive forms ( 3,4). We describe a patient with id­iopathic striopallidodentate calcification who ex­hibited, in addition to an extrapyramidal move­ment disturbance and mild dementia, a marked abnormality of eye movement not previously re­ported in association with this disorder. From the Section of Neurology ( G. T. L., M. E. C.) Brockton/ West Roxbury Veterans Administration Hospital, Department of Neurology, Harvard Medical School, Division of Neurology, Department of Medicine, Brigham and Women's Hospital, Har-vard- Longwood Neurology Training Program, Boston, Massa­chusetts; and the Department of Neurology ( J. L. S.), North­western Memorial Hospital, Lakeside Veterans Administration Hospital, Northwestern University Medical School, Chicago, Illinois, U. S. A. This paper was presented in part at the 44th annual meeting of the American Academy of Neurology, San Diego, California, May 1992. Address correspondence and reprint requests to Dr. Jeffrey L. Saver, Department of Neurology, Northwestern Memorial Hospital, 233 East Erie Street, Suite 500, Chicago, IL 60611, U. S. A. REPORT OF A PATIENT A 63- year- old, right- handed man developed progressive difficulty speaking, gait disorder, and diminished hygiene. Four years before admission he began to fall increasingly and walk with small, quick steps. He occasionally maintained his upper limbs in unusual postures for extended periods of time. He became reticent about talking, and spoke with decreased volume. Personal hygiene deterio­rated, resulting in eviction from his apartment. He continued to drive and handle financial affairs, but avoided interpersonal interactions. He complained of occasional double vision, which he character­ized poorly. " Shell shock" was diagnosed 40 years earlier and throughout adulthood he had difficulty with anxiety. There was no history of exposure to neu­roleptic agents, and he was taking no medications at the time of admission. He was one of 15 siblings 29 30 }. L. SAVER ET AL. and had one son. The only family history of neu­rologic impairment was a maternal female first cousin who had received a diagnosis of Parkin­son's disease ( details of this case were unavailable for review). The general physical examination was unre­markable, including normal stature. The retina was normal, and there were no cataracts or Kay-ser- Fleischer rings. On mental status examination, the patient was anxious and withdrawn, but fully oriented and attentive. Speech was moderately dysarthric and hypophonic; underlying language function was intact. Constructions and verbal memory were mildly impaired. He had significant difficulty with tests of frontal systems, including inability to acquire the Luria hand sequence and errors of commission on go- no go testing and writ­ten alternating motor tasks. His visual acuity was 20/ 30 OS, 20/ 20 OD, and the visual fields were full to confrontation. There was a 1.5- mm anisocoria, left greater than right, but the pupillary light reactions were normal and there was no dilation lag, consistent with physio­logic anisocoria. Convergence and eyelid opening were normal. There was marked difficulty gener­ating saccades to command in all directions of gaze. Voluntary saccades both to visual (" Look at my finger") and nonvisual (" Look left," " Look right") targets were affected. No head thrusting movements were observed. On several occasions, full but slow reflexive saccades to novel visual and auditory stimuli occurring during the course of the examination were observed. Upward pursuit and voluntary saccades were limited to approximately 15 degrees in each eye ( Fig. 1A) and were im­proved to 30 degrees by oculocephalic maneuver. Voluntary and oculocephalic downward eye movements were full ( Fig. IB). Voluntary horizon­tal eye movements were reduced in amplitude and markedly impersistent ( Fig. 1C); horizontal pursuit showed " catch- up" corrective saccades. In con­trast, oculocephalic horizontal eye movements were smooth and full ( Fig. ID). Optokinetic nystagmus was present in all directions, although amplitude was diminished. He exhibited a staring, stiff, smiling face, and the head tended to be upturned. There was signif­icant rigidity of axial greater than limb muscles, with prominent involvement of the neck exten­sors. There was no cogwheeling. There were infre­quent athetotic movements of the upper extremi­ties bilaterally, with occasional sustained dystonic postures. There was mild bradykinesia. There was no weakness, muscle atrophy, sensory loss, or ataxia. Gait was narrow based with decreased arm FIG. 1. Extraocular movements demonstrating impair­ment of upgaze and voluntary horizontal saccades. Attempted fixation on a target located: ( A) above his head ( the photograph was shot from slightly below the horizontal meridian), ( B) below his head, ( C) to his right, and ( D) directly ahead with the examiner turning his head to the left. The oculocephalic maneuver ( D) corrects his defective generation of voluntary sac­cades to the right. swing and tendency to hold both arms stiffly be­hind the back (" peacock gait"). Deep tendon re­flexes were brisk and symmetric, with 2- 3 beats of clonus at the ankles. The plantar responses were flexor. Snout and glabellar reflexes were elicited. A complete blood count, urinalysis, serum elec­trolytes, lactate, alkaline phosphatase, transami­nases, folic acid, cobalamin, sedimentation rate, rapid plasma reagin, thyroid, ceruloplasmin, cop­per, and cerebrospinal fluid ( CSF) tests were all normal. The serum calcium was 9.1 mg/ dl ( normal 8.5- 10.5 mg/ dl), ionized serum calcium 5.0 mg/ dl ( 4.5- 5.3 mg/ dl), inorganic phophorus 3.9 mg/ dl ( 2.5- 4.5 mg/ dl), and C- terminal parathyroid hor­mone 330 pg/ ml ( 50- 340 pg/ ml). A 24- hour urine collection showed normal excretion of copper and calcium. A slit lamp examination was unremark­able. Electrocardiogram showed sinus bradycar- / Neuro- Ophthalmol, Vol. 14, No. 1, 1994 STRIOPALLIDODENTATE CALCIFICATION 31 dia. An electroencephalogram was normal. Radio­graphic films of the hand did not reveal develop­mental osseous abnormalities. Serial cranial CT studies obtained 2 years apart showed progres­sive, symmetric calcification of the striatum, mid­brain, deep cerebellar nuclei, and subcortical white matter ( Fig. 2). Magnetic resonance imaging ( MRI) likewise showed characteristic findings of stnopal­lidodentate calcification ( Fig. 3). Treatment with trihexyphenidyl hydrochloride produced mild improvement in axial dystonia, dysarthria, and eye movements, but was discon­tinued due to visual blurring and urinary reten­tion. COMMENT A wide range of movement disorders have been reported in patients with idiopathic calcification of the basal ganglia. Rarely, however, have oculomo­tor abnormalities been noted, and then only to mild degree ( 5). Fahr, in the report that led to his eponymic association with this condition, noted diplopia but normal ocular movements in his pa­tient ( 6). Chavany and colleagues ( 7) observed loss of convergence in their patient, but no other ocu­lomotor disturbance. In Kasanin and Crank's case ( 8), a sluggish pupillary reaction to light on the right was noted. Our patient demonstrated the characteristic mo­tor, neuropsychiatric, and neuroradiologic fea­tures of idiopathic striopallidodentate calcification, but, additionally, exhibited a marked supranuclear disturbance of eye movements characterized by defective initiation of voluntary saccades, limita­tion of upgaze, and impaired smooth pursuit, with sparing of the oculocephalic reflex. These prominent oculomotor disturbances, in combination with the extrapyramidal disorder and mild dementia, suggested the diagnosis of pro­gressive supranuclear palsy. All the salient find­ings of progressive supranuclear palsy ( 9) were FIG. 2. Serial cranial CT scans demonstrating progressive striopallidodentate calcification. ( A) CT scan obtained 2 years before admission. There are dense, symmetric calcifications of the dentate, caudate, and lenticular nuclei, ventral rostral midbrain, deep white matter of the frontal, parietal, and occipital lobes, and cortical gyri of the occipital poles. ( B) CT scan on admission. Compared to the earlier study, there is increased calcification of the basal ganglia and subcortical white matter and enlargement of the lateral ventricles and perisulcal space. I Neuro- Ophthalmol, Vol. 14, No. 1, 1994 32 }. L. SAVER ET Ah. A i j ^ ^ ^ ^ - QHKCIII • w ^ ! & \ * V A. / * • « \ / ^•^ H HL^^ I ^ FA 7* 1 A f 4jjys- \ f ••• \!$* y ^ 1 ^ ^ c p '• it ^'•^^ H $ 4% it ' 1 ^ -*, M $ A ' 1 - " ^ ~ tf ' 4 IV "^ FIG. 3. MRI obtained on admission demonstrates multifocal, punctate T1 and T2 dark- signal abnormalities in caudate, putamen, globus pallidus, and dentate nuclei bilaterally and in right centrum semiovale. ( A) On T1 sequences ( TR 800 ms; TE 20 ms) these low- signal areas are surrounded by regions of increased signal intensity. Gadolinium infusion produced no change ( not shown). On proton density [( B) TR 2500 ms; TE 30 ms and T2 ( C) TR 2500 ms; TE 80 ms] sequences there is additional periventricular bright signal. present, including a progressive disorder, onset around age 60, extrapyramidal rigidity, extensor rigidity of the neck, bradykinesia, gait impairment, bulbar palsy, dementia, and a primarily supranu­clear ophthalmoparesis with impaired saccadic and pursuit eye movements. Other aspects of our patient's disorder, while atypical of progressive supranuclear palsy, have been observed infrequently in that condition. Choreoathetosis is unusual in progressive supra­nuclear palsy, but it has been noted ( for example, case 4 in the original report of Steele and cowork­ers ( 10). The most common initial gaze deficit in progressive supranuclear palsy is limitation of looking downward, but difficulty of upgaze ex­ceeding that of downgaze has been reported in a J Neiiro- Ophtlmlmol, Vol. 14, No. 1, 1994 STRIOPALLIDODENTATE CALCIFICATION 33 minority of patients ( 10). Consequently, anoma­lous findings in our patient would allow a diagno­sis of progressive supranuclear palsy to be ques­tioned, but not excluded, on clinical grounds alone. However, the absence of neuroradiologic findings supportive of progressive supranuclear palsy- atrophy of the midbrain tegmentum, supe­rior colliculi, and pons ( 11,12)- in addition to the atypical clinical findings and the progressive intra­cranial calcification revealed on computed tomog­raphy ( CT) scanning, make it improbable that he had progressive supranuclear palsy in addition to striopallidodentate calcification. Other, less common causes of progressive su­pranuclear ocular dysmotility are also unlikely. Absence of similar illness among numerous first-degree relatives, lack of a history of perinatal in­sult, length of course, site of geographic origin, lack of gastrointestinal symptoms, and normal blood smear militate against kernicterus, Nie-mann- Pick disease, neuroacanthocytosis, familial Parkinson- dementia syndrome, Western Pacific amyotrophic lateral sclerosis- parkinsonism- demen-tia complex, Whipple's disease, and Creutzfeldt- Jakob disease. Diffuse Lewy body disease, cortico-basal ganglionic degeneration, and olivopontocere­bellar atrophy may not be conclusively excluded in the absence of pathologic examination, but would present such a clinical picture only in highly unusual cases. Our patient's deficit in initiating voluntary sac­cadic eye movements is consonant with recent neurophysiologic and clinical data, indicating a major role for the basal ganglia in the generation of voluntary saccades ( 13,14). Widespread subcorti­cal, midbrain, and cerebellar calcification may also have contributed to our patient's complex oculo­motor disorder, by disrupting the multiple de­scending, parallel pathways that mediate saccade and smooth pursuit movements. In view of the common occurrence of oculomotor abnormalities in other progressive basal ganglia disorders, such as Parkinson's disease, progressive supranuclear palsy, and Huntington's disease, we find it sur­prising that significant impairment of eye move­ments has not been reported in idiopathic calcifi­cation of the basal ganglia. Careful analysis may reveal cases similar to ours, and perhaps allow the identification of characteristic oculomotor deficits that will aid in distinguishing striopallidodentate calcification from other progressive extrapyramidal disorders of mid and late life. Acknowledgments: The a u t h o r s t h a n k Richard Schwartz, M. D., Brigham a n d Women's Hospital for aid in interpretation of neuroradiologic studies. 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