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Show " )9tl6 Rave" Press. New York New Computed Tomography Scan Finding in Hallervorden-Spatz Syndrome Marion P. Van Kirk, M.D., Paul D. Larsen, M.D., and Patrick S. O'Connor, M.D. The case of an ll-year-old female with the clinical findings of Hallervorden-Spatz syndrome. including progressive dystonia, dysarthria, disturbances of gait. and retinal pigmentary degeneration, is presented. The differential diagnosis of childhood dystonia "nd retinal pigmentary degeneration associated with nt'urologicaI conditions is discussed. The prcsenct' of b.,saI ganglia densities on computed tomography scanning in thi patient may aid in future premorlem diagnosis llf this rare disease. From the Department of Ophthalmology (Drs. Van Kirk and O'Connor) and the Division uf Pediatric Neurology (Dr. Larsen), Univer ity of Texas Health Science Center. San Antonio, Texas. Address correspondence and reprint requests tu Paul D. Larsen, M.D., Division of Pediatric Neurology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio. TX 78284. U.S.A. 86 Hallervorden-Spatz syndrome, or pigmentary degeneration of the globus pallidus and substantia nigra, is a rare, familial (autosomal recessive), and fatal disorder first described in 1922 by authors of the same names as a progressive degenerative disorder of the basal ganglia with dystonia, dysarthria, disturbances of gait, and eventual dementia (1). About one-third of the patients have an associated pigmentary degeneration of the retina (2). Onset is early, usually between ages 2 and 10, with 809C prior to age 15 (2). There is no known etiology and no known biochemical abnormality, although an inborn error of metabolism has been suggested (3). The disease has been induced experimentally in animals by the intravenous infusion of manganese chloride, ferrous sulfate, and sodium selenite (4). The common denominator in these experiments was the resulting liver damage leading to an encephalopathy, suggesting that Hallervorden-Spatz, like Wilson's disease, belongs to the family of hepatic encephalopathies, and, as in Wilson's disease, there may be some inborn error of metabolism resulting in the subsequent increased deposition of iron pigment in the basal ganglia in this disease. At present, however, the diagnosis depends on the clinical findings as well as neuropathology, which shows brown discoloration of the globus pallidus and the reticular zone of the substantia nigra with iron pigment deposition in these areas (2,5,6). Microscopically, spheroid bodies (axonal swellings) OCCur in the pallidonigral regions and cerebral cortex (2,6,7). Computed tomography (CT) scans thus far have been normal (7,8) or showed severe diffuse cerebral atrophy with striking caudate atrophy and ventricular enlargement (9). We wish to present a case of probable Hallervorden-Spatz syndrome (premortem) with a CT scan finding that to the best of our knowledge has not yet been reported in this condition. CT SCAN AND HALLERVORDEN-SPATZ SYNDROME 87 CASE REPORT The patient was an ll-year-old Latin American female with a younger half-brother and a halfsister who were healthy. She weighed 6 Ib 7Y2 oz at birth and had an uneventful delivery. Her family noted an unusual crawling pattern and tendency to awkwardness since infancy. Nyctalopia also had been noted since infancy, as well as a left esotropia which was surgically corrected in March 1983. At that time, a fundus picture consistent with retinitis pigmentosa was described. No other problems were detected until age 8 (1982), at which time she developed posturing with left upper extremity extensor rigidity and wrist flexion. Over the next few months, motor impairment of the left side progressed, resulting in stiffness and a dystonic gait. She also developed difficulty with speech (stuttering) and involvement of her right arm. The patient never showed mental deterioration and was able to do average schoolwork in a special classroom. There was no history of fever, steatorrhea, jaundice, or seizures, and her family history was negative. At the time of admission in 1984 at age 11, her height and weight were less than the fifth percentile, and her head circumference was in the 50th percentile. She was alert and cooperative and smiled appropriately, although there was very little facial expression and diminished spontaneous facial movement. The patient was severely dysarthric and her speech had a marked dystonic quality making speech difficult. Dystonic posturing of the trunk with retroflexion of the head and opisthotonos made it appear as though she were sliding out of a chair. The extremities were dystonic and her feet were twisted in an equinovarus position. A dromedary-type gait with severe lordoses was noted with the right upper extremity postured behind the patient's back. She required support because of the degree of retropulsion and dystonia. The deep tendon reflexes were diffusely hypertonic with ankle clonus and bilateral Babinski reflexes. Sensory and cerebellar systems were intact. Ophthalmologic examination revealed a best corrected vision of 20/30 in both eyes, normal pupils, normal intraocular pressures and anterior segments. Motility was full with a 12-prismdiopter concomitant left esotropia. There was no nystagmus. The visual fields were constricted. Fundus examination revealed normal optic nerves, vessels, and maculae, but a mottled background in the periphery with pigment deposits in the form of bony spicules 3600 O.U. (Fig. FIG. 1. Photograph of the patient's right fundus, demonstrating normal disc and vessels with midperipheral bone spiCUle pigmentation. 1). Both the photopic and scotopic electroretinograms were extinguished. Color vision (0-15) and pattern visual evoked responses were normal, suggesting sparing of central vision in the face of a widespread retinal dystrophy. The remaining ex- FIG. 2. CT scan showing bilateral basal ganglia densities (see arrow), probably due to pseudocalcareous deposits. I Clill NfIlTlI-olll1ll,allllol. Vol. 6. No.2. 1986 88 M. P. VAN KIRK ET AL. TABLE 1. Dystonia associated with other hereditary neurologic disorders Wilson's disease Huntington's disease Hallervorden-Spatz syndrome GM·1 gangliosidosis Hexosamidase A and B deficiency Glutaric acidemia Juvenile dystonic lipidosis (Juvenile Niemann-Pick disease) amination, including skin and abdomen, was normal. Lab studies, including complete blood cell count, chemical profile with cholesterol and triglycerides, urinalysis, serum protein electrophoresis, urine and serum copper, ceruloplasmin, serum vitamin A, serum vitamin E, parathyroid hormone, and total calcium, were normal. Electron microscopy of the patient's peripheral blood buffy coat was negative for ceroid lipofuscinosis. Computed tomography of the head revealed small areas of increased density similar to calcifications in the globus pallidus bilaterally (Fig. 2), DISCUSSION Clinically, dystonia involves sustained, involuntary twisting movements which affect muscle groups in the trunk, limbs, face, and neck. The movements are usually slow, but may be rapid and then are termed dystonic spasm (10). The dystonic states can be classified into primary or secondary dystonias (11). The primary dystonias have no other neurological system involvement, have ~o predisposing factors present, and may be hereditary, such as dystonia musculorum deformans, or idiopathic, such as the focal dystonia, torticollis, or blepharospasm (10). On the other hand, secondary dystonias may involve other neurological systems and include those dystonias associated with other hereditary neurologic disorders such as Hallervorden-Spatz syndrome (10,11) (Table 1), and those associated with the environment (10,11) (Table 2). Whenever a child presents with torsional dystonia after many of the abo.ve diseases are eliminated by history or examination, several conditions should be considered TABLE 2. Dystonias associated with the environment Perinatal cerebral injury Infection Postinfectious Head trauma Toxins: manganese. carbon monoxide Drugs: levadopa, antipsychotics, anticonvulsants IOiu rllra·or/Mho/m"l. Vol. Ii. No 2. 19RIi TABLE 3. Differential diagnosis of a child with dystonia Dystonia musculorum deformans Hallervorden-Spatz syndrome Juvenile Huntington's chorea Wilson's disease Juvenile Niemann-Pick disease (Table 3), including: (a) dystonia musculorum deformans (12) (onset usually in the first and second decade, with distortion of postures in the trunk and limbs as an isolated neurological finding); (b) Hallervorden-Spatz syndrome; (c) juvenile Huntington's chorea (usually characterized by rigidity, seizures, and dementia); (d) Wilson's disease (abnormal copper metabolism, liver disease, tremor, and rigidity); and (e) juvenile Niemann-Pick disease (progressive dementia, dysarthria, seizures, vertical gaze palsies) (2). Adding pigmentary retinal degeneration to the clinical picture introduces another list of possible conditions (Table 4), including: (a) HallervordenSpatz syndrome; (b) Cockayne's syndrome (small, retarded child with neurosensory deafness and photosensitive dermatitis); (c) Vitamin E deficiency (fat-soluble vitamin malabsorption, areflexia, ataxia, sensory deficits, ophthalmoplegia); (d) Bassen- Kornzweig (abetalipoproteinemia) (similar features as with vitamin E deficiency, with additional findings of acanthocytosis and decrea. sed cholesterol); (e) ceroid lipofuscinosis (juvenil~ ama~rotic idiocy or Spielmeyer-Vogt, and late mfantlle amaurotic idiocy or Batten- Bielschowsky disease; the initial manifestation is usu~lly seizures, then myoclonus, macular degeneration, and optic atrophy); (f) Refsum's disease (neurosensory deafness, ichthyosis, peripheral neuropathy); and (g) Kearns-Sayre syndrome (ophthalmoplegia, ragged-red fiber myopathy) (2,13). Naturally, not all of these entities are clinically di.st~nct and there may be overlap; but with the chmcal findings and laboratory data of our patient, we feel that, even without neuropathological evi- TABLE 4. Neurologic degenerative conditions associated with pigmentary retinal degeneration Hallervorden-Spatz syndrome Cockayne's syndrome Vitamin E deficiency Bassen-Kornzweig Ceroid lipofuscinosis (Spielmeyer-Vogt and Batten-Bielschowsky) Refsum's disease Kearns-Sayre syndrome CT SCAN AND HALLERVORDEN-SPATZ SYNDROME TABLE 5, Twenty-six conditions previously described in association with radiographically identified basal ganglia calcification" 89 Idiopathic hypoparathyroidism Secondary hypoparathyroidism Pseudohypoparathyroidism Pseudo-pseudohypoparathyroidism Hyperparathyroidism Hypothyroidism Birth anoxia Carbon monoxide intoxication Lead intoxication Fahr's syndrome (ferrocalcinosis) Familial idiopathic symmetrical basal ganglia calcification Hasting-James syndrome MELAS (Metabolic encephalopathy lacllc acidosis and stroke) • See references 16-18. dence, the diagnosis of Hallervorden-Spatz syndrome is established. As can be noted, Hallervorden- Spatz syndrome is the only condition included in both differential diagnosis lists. Of special interest in our case is the finding of basal ganglia density on computed tomography. Whether these represent the deposition of iron pigment granules seen histopathologically or the accompanying pseudocalcareous deposits previously reported is unclear (14). Although calcium concentrations have been reported to be elevated in the basal ganglia of Hallervorden-Spatz syndrome (15), iron is the predominant trace element which is elevated in this disease, and given its electron density may very well be the major contributor to the CT scan findings in our patient. MRI would be helpful in determining the relative contribution of iron versus calcium, as iron would be readily visible while calcium would not. Even though the hyperdense basal ganglia lesions in our patient may be from iron deposits, on CT scan they are indistinguishable from the appearance of calcifications, and therefore we recommend that Hallervorden-Spatz syndrome be added to the list of diseases which can present with the appearance TABLE 6. Diagnostic workup for dystonia and retinal degeneration Complete blood cell count Chemical screen Vitamins E and A Copper Ceruloplasmin Parathyroid hormone Calcium Electron microscopy of buffy coat ERG Visual-evoked response Color vision CT scan of the head Cockayne's syndrome Lipoid proteinosis Tuberous sclerosis Parkinsonism Vascular disease Cerebral hemorrhage Radiation therapy Methotrexate therapy Cytomegalic inclusion disease Encephalitis (measles. chicken pox) Toxoplasmosis Cysticercosis Kearns-Sayre syndrome of calcifications of the basal ganglia on CT scan. There are 26 conditions previously described as being associated with such calcifications (Table 5) (16-18). Among the more common are parathyroid disease, birth anoxia, carbon monoxide and lead intoxication, Kearns-Sayre syndrome, Fahr's syndrome, Cockayne's syndrome, toxoplasmosis, cytomegalic inclusion disease, tuberous sclerosis, and Parkinson's disease. Perhaps in future cases of Hallervorden-Spatz syndrome, the finding of basal ganglia densities will aid in the early premortem diagnosis of this syndrome. SUMMARY When the ophthalmologist is faced with a child displaying dystonia and a retinal picture suggestive of retinitis pigmentosa, further neurological evaluation (Table 6) and consultation are in order. Studies should include a complete blood cell count (to check for acanthocytes as seen in BassenKornzweig disease); chemical screen for triglycerides and cholesterol (which are low in abetalipoproteinemia); vitamin E levels (to rule out vitamin E deficiency); urine and serum copper and ceruloplasmin (Wilson's disease); parathyroid hormone and calcium (parathyroid disease); and ultrastructural electron microscopy of the peripheral blood buffy coat looking for ceroid bodies in leukocytes as seen in ceroid lipofuscinosis. Electrophysiologic studies of the eye should also be obtained. Finally, computed tomography of the head may be helpful if basal ganglia densities are found, suggesting the diagnosis of Hallervorden-Spatz syndrome when combined with dystonia and retinal pigmentary degeneration. Acknowledgment: This study was supported in part by a Research to Prevent Blindness Development Award I eli" Nrllf<l'oJllltlmll/lol. Vol. 6. No.2. 19R/i 90 M. P. 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