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Hallervorden-spatz syndrome Clinical and magnetic resonance imaging correlations.

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Syndrome: Clinical and
Magnetic Resonance
Imaging Correlations
K. D. Sethi, MD, MRCP,’ R. J. Adams, MD,”
D. W. Loring, PhD,’ and T. El Gammal, MDt
Two women with a presumptive diagnosis of Hallervorden-Spatz syndrome had a combination of dystonia and
parkinsonism. One had retinitis pigmentosa. Neuropsychological testing revealed decreased verbal fluency
and visuoconstructional and motor deficits. Magnetic
resonance imaging performed with a high-field-strength
unit (1.5 Tesla) showed striking abnormalities i n the
globus pallidus bilaterally (“eye-of-the-tiger” sign).
Magnetic resonance imaging may prove useful in the
diagnosis of Hallervorden-Spatz syndrome.
Sethi KD, Adams RJ, Loring DW, El Gammal T.
Hallervorden-Spatz syndrome: clinical and
magnetic resonance imaging correlations.
Ann Neurol 1988;24:692-694
Hallervorden-Spatz disease ( H S D ) is characterized by
extrapyramidal rigidity, dystonia, retinal degeneration,
and dementia. Pathologically there is iron deposition in
t h e globus pallidus and zona reticularis of substantia
nigra and there are axonal spheroids in these and other
areas of t h e brain [l). The diagnosis is usually made
post mortem. We present 2 cases with neuropsychological testing and magnetic resonance imaging (MRI).
Case Reports
Patient I
A 20-year-old woman had a 1-year history of progressive
difficulty with night vision and repeated forceful eye closure
aggravated by sudden noise and attempted eye opening. The
only neurological findings were frequent blepharospasm, repetitive slow tongue protrusion, and tapetoretinal degeneration. There were no Kayser-Fleischer rings. Electroretinography showed a flat tracing in both eyes. The following tests
were normal or negative: a cranial computed tomographic
scan, electroencephalography, routine blood studies, serum
copper, ceruloplasmin, urine metabolic screen, antinuclear
antibodies, erythrocyte sedimentation rate, and a cerebrospinal fluid examination. Initially a psychiatric diagnosis of conversion reaction with blepharospasm was made. Over the
next 2 years the blepharospasm became more severe, and the
From rbe Deparrmenrs of “Neurology and tNeuroradiology, Medical College of Georgia, Augusta, GA.
Received Feb 8, 1988, and in revised form May 17. Accepted for
publication May 20, 1388.
Address correspondence to D r Sethi, Department of Neurology,
Medical College of Georgia, Augusra, G A 30912.
patient began falling without loss of consciousness. A tremor
developed in both hands and the lower jaw and her intellectual functions declined. Reexamination showed facial g r h a c ing, severe blepharospasm, and tongue protrusion. There
was a rest tremor of both hands, tongue, and jaw and cogwheel rigidity of both arms. Gait was slow and wide-based
with reduced arm swing. Neuropsychological testing showed
a verbal I Q of 7 3 and deficits in verbal and visuomotor functions and motor sequencing.
Drug therapy-including trihexyphenidyl, reserpine, haloperidol, chlorpromazine, low-dose bromocriptine, and I-dopdcarbidopa-was unsuccessful. Currently she receives 4
gm of vitamin C per day.
Patient 2
This 38-year-old woman was well until ‘age 14, when she
began arching her body backward, falling out of the chair if
unsupported. At age 16 a diagnosis of dystonia was made.
She responded to chlorpromazine treatment and finished
high school. She slowly deteriorated despite medication and,
at age 20, developed progressive difficulty with mouth closure. At age 32 she began to fall frequently. Attempts to
withdraw chlorpromazine resulted in worsening symptoms
of back arching and jaw dystonia. Chlorpromaine was
stopped at age 36, but the difficulty in walking and frequent
falling has continued.
O n most recent examination, she was severely dysarthric
because of marked jaw dystonia and had a slow tremor of
tongue and jaw. She had dystonia of the right hand. Gait was
slow and hesitant. Reflexes were normal and there was no
Babinski sign. IQ was difficult to test, but severe motor and
visuospatial deficits were present. The tone in her arms was
increased but was difficult to characterize as either rigidity or
spasticity. Computed tomographic scan of the head was normal.
Magnetic Resonance Imaging
MRI scan was performed with a spin echo sequence on a GE
1.5-Tesla Signa unit. Both proton density (TR = 2,000
msec; TE = 25 msec) and TZ-weighted (TR = 2,000 msec;
TE = 50 msec) images were obtained. Five-millimeter axial
and coronal images revealed striking abnormalities in both
patients (Figs 1 and 2). W e have called the abnormality the
“eye-of-the-tiger” sign. The low signal normally seen on ’r2weighted images in the globus pallidus was markedly exaggerated. This low-signal area surrounded a relatively circumscribed region of high signal. The low signal was less
evident but still present on proton density images. There was
no abnormality in the brainstem including substantia nigra,
cerebellum, or cerebral hemispheres.
Hallervorden and Spatz described a progressive disord e r (HSD) characterized by rigidity, dystonia, and progressive dementia in 1922 [ 1). Pathological changes
mainly involved globus pallidus and zona reticularis of
the substantia nigra. Subsequent reports noted pyramidal signs and retinitis pigmentosa as additional findings.
Also, cases with pathological changes similar to those
o f HSD but without extrapyramidal dysfunction were
called HSD, leading to confusion in t h e literature. It
Copyright 0 1988 by the American Neurological Association
Fig 2. Magnetic resonance scan T2-weighted images ( T R =
2,000; TE = SO1 Jhow a decreased signal localized to the globus
pallidus surrounding an area of increased signal.
Fig 1. Magnetic resonance scan T2-weighted images (TR =
2,000; TE = 50) show “eye-ofthe-tiger” sign.
has been suggested that the term Hallervorden-Spatz
disease be reserved for typical cases with onset in the
first or second decade, extrapyramidal symptoms, positive family history, and characteristic pathological findings, and the term Hallervorden-Spatz syndrome be used
for other cases [l]. Since our patients have neither a
positive family history nor pathological confirmation,
we employ the term Hallervorden-Spatz syndrome.
Both our cases have strikingly similar clinical and
radiological features. Following normal early childhood
development, both patients developed dystonia, rigidity, progressive intellectual deterioration, and mark-
edly impaired postural reflexes. Dystonia as a prominent and early feature has been reported previously C2,
31. Speech difficulty, including dysarthria and muteness, is almost universal. The impairment of postural
reflexes also noted in this disorder was very marked in
our patients and resulted in frequent falls.
At present there is no reliable way to make a diagnosis of HSD while the patient is alive. There have
been reports of delayed iron disappearance over the
basal ganglia after an injection of 59Fe 141. However,
these studies are cumbersome and generally unavailable. An increased uptake of radioactive Fe by fibroblasts of patients with H S D has been reported I S ] but
not confirmed. Recently Perry and colleagues 161 described low activity of the enzyme cysteine deoxygen-
Brief Communication: Sethi et al: Hallervorden-Spatz Syndrome 693
ase and low levels of y-aminobutyric acid in the globus
pallidus of patients with HSD. However, no cystine
was detectable in the cerebrospinal fluid of one patient
studied and y-aminobutyric acid concentration was
normal. The authors thought it unlikely that examination of cerebrospinal fluid would prove useful in detecting neurochemical abnormalities localized tc) the
globus pallidus.
Computed tomographic scanning has been reported
to show generalized atrophy especially affecting the
striatum { 7 ) or increased densities limited to the
globus pallidus 18-10]. At best these abnormalities are
nonspecific. The computed tomographic scan was normal in both our patients.
MRI has been useful in the diagnosis of iron storage
diseases [ 11, 12f and in studying normal iron distribution in the human brain [13). There is evidence that
MRI using a high-field-strength magnet improves delineation of brain iron 114).
Iron acting as a paramagnetic substance causes a proton relaxation effect on neighboring hydrogen nuclei,
resulting in a decrease in T1 and T2 relaxation times.
O n T2-weighted images the decrease in relaxation
time results in a decreased signal C12, 151. This effect
has been shown to occur in superficial siderosis of the
brain and at the edge of old hematomas 116, 17). The
striking low attenuation limited to the globus pallidi
bilaterally in our patients suggests iron accumulation.
Though this appearance on MRI scan may be consistent with the appearance of old hematomas, the bilateral symmetrical nature of the lesion and the clinical
picture rule against this possibility.
The central high signal on the MRI is more difficult
to explain but has been noted previously 1141. It may
be due to intense gliosis 1181 or increased water content due to loss of cellular elements 1151. The exact
nature of the high signal awaits pathological confirmation. Previous reports 114, 19, 201 have described
MRI findings in patients thought to have HSD. The
lack of clinical details and different imaging parameters
in one report {19] preclude comparison with the MRI
of our cases. The clinical features related in one report
do not suggest HSD, and although low signal was seen
on MRI (0.35 Tesla), it was not restricted to globus
pallidus E20). In a study of movement disorders and
brain iron using a high-field-strength magnet (1.5
Tesla), Rutledge and colleagues described 4 cases with
clinical and familial evidence of H S D 1141. The MRI
findings of markedly decreased signal in globus pallidus and central increased signal are similar to those
seen in our cases.
In summary, we have discussed 2 patients with clinical findings consistent with HSD, but without a family
history of the disease. The MRI appearance is very
similar to that for the familial cases previously described using a high-field-strength MRI [14) and sup-
ports the diagnosis of HSD. We conclude that it may
be possible to diagnose H S D while the patient is alive
through clinical and MRI findings.
We thank Cathy Hallex and Kara Summers for typing this manuscript.
Presented at the 112th Annual Meeting of the American Neurological Association, Oct 18-21, 1987, San Francisco, CA.
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694 Annals of Neurology Vol 24 No 5 November 1988
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correlation, clinical, syndrome, magnetic, imagine, spatz, hallervorden, resonance
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