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Show 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. REFERENCES 1. Cummings JL, Gosenfeld LF, Houlihan JP, McCaffrey T. Neuropsychiatric disturbances associated with idiopathic calcification of the basal ganglia. Biol Psychiatry 1983; 18: 591- 601. 2. Lowenthal A. Striopallidodentate calcifications. Hand Clin Neurol 1986; 49: 417- 36. 3. Ellie E, Julien J, Ferrer X. Familial striopallidodentate calcifications. Neurology 1989; 39: 381- 4. 4. Manyam BV, Bhatt MH, Moore WD, Devleschoward AB, Anderson DR, Calne DM. Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies. Ann Neurol 1992; 31: 379- 84. 5. Rossazza C, Yesou C, Guerois M. Les signes ophthal-mologiques associes a la maladie de Fahr. Bull Mem Soc Fr Ophtalmol 1983; 95: 445- 8. 6. Fahr T. Idiopathische Verkalkung der Hirngefasse. Zen-tralbl Allg Pathol Anat 1930; 50: 129- 33. 7. Chavany JA, Bogaert LV, Houdart R. Aspects extrapyrami-daux de la " calcification vasculaire intracerebrale nonarte-rioslereuse idiopathique" de Fahr. Monatsschr Psychiatr Neurol 1949; 117: 77- 99. 8. Kasanin J, Crank RP. A case of extensive calcification in the brain. AMA Arch Neurol Psychiatry 1935; 34: 164- 78. 9. Duvoisin RC, Golbe LI, Lepore FE. Progressive supranuclear palsy. Can f Neurol So' 1987; 14: 547- 54. 10. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy. Arch Neurol 1964; 10: 330- 59. 11. Savoiardo M, Strada L, Girotti F, et al. MR imaging in progressive supranuclear palsy and Shy- Drager syndrome. / Comp Assist Tomogr 1989; 13: 555- 60. 12. Stern MB, Braffman BH, Skolnick BE, Hurtig HI, Grossman RI. Magnetic resonance imaging in Parkinson's disease and parkinsonian syndromes. Neurology 1989; 39: 1524- 6. 13. Leigh RJ, Zee DS. The neurology of eye movements, 2nd Ed. Philadelphia: FA Davis, 1991. 14. Hikosaka O. Role of basal ganglia in saccades. Rev Neurol 1989; 145: 580- 6. I Neuro- Ophtlmlmol, Vol. 14, No. 1, 1994 |