Pathogenesis and Pathophysiology. Hallervorden- Spatz disease (HSD) is a rare autosomal recessive disorder associated with excessive iron deposition in the globus pallidus (GP). y The most striking autopsy finding in HSD patients is the asymmetrical rust-brown pigmentation of the GP and zona reticulata of the substantia nigra (SN). The iron pigmentation occurs both extracellularly and intracellularly but is predominantly found in astrocytes, microglia, and neurons. "Mulberry" concretions are also typically present in the extracellular space. Numerous and large spheroid bodies, identified by myelin staining and surrounded by pigment granules, are typically present throughout the medial GP, SN zona reticulata, cortex, and subthalamic nucleus. y The spheroid bodies apparently represent degenerating myelinated axons.
Clinical Features and Associated Disorders. HSD was initially described in a single family of 12 children, three of whom died at birth; eight of the remaining nine developed athetosis, tremor, and visual difficulties. Dystonia and rigidity are the major hallmarks of this childhood illness, but other associated features include gait and posture disturbances, chorea, athetosis, tremor, dysarthria, blindness with retinitis pigmentosa, intellectual decline, spasticity, and seizures. Myoclonus is rare and usually is a preterminal sign. Although the onset usually occurs in the first decade of life, rare patients with adult-onset HSD starting in the fourth to sixth decade and presenting as parkinsonism have been described. y
Differential Diagnosis. HSD has a wide spectrum of presentation and therefore a potentially large differential diagnosis. A disease of iron deposition in the basal ganglia, HSD shares some features with other disorders associated with deposition of metals, such as Wilson's disease and manganese toxicity. Other disorders with overlapping clinical features include juvenile Huntington's disease, neuro- acanthocytosis, and neuronal ceroid lipofuscinosis.
Evaluation. CT scans reveal high signal intensity in the medial GP, and MRI demonstrates decreased signal intensity in the GP on T2- or proton density-weighted images; these abnormalities are produced by iron deposition bilaterally in the pallidum. y In some cases, the center is hyperintense, giving rise to the term "eye of the tiger" sign. Ophthalmological examination may be particularly helpful because it may show optic degeneration and retinitis pigmentosa.
Management. There is no specific treatment for HSD. Chelation therapy to remove excess iron accumulation in the basal ganglia has not been useful. Parkinsonism in some patients has responded to levodopa and bromocriptine therapies, but anticholinergic agents have failed to improve symptoms of tremor, dystonia, or bradykinesia. The choreoathetosis may benefit from benzodiazepines, but dopamine antagonists are generally not used because of the risk of worsening parkinsonism. Antiepileptic drugs are useful for the control of seizures. Supportive care and physical, occupational, and speech therapy should also be instituted when appropriate. [d
Prognosis and Future Perspectives. The mean duration of the disease is 11 years, and 45 percent of patients die before reaching the age of 20 years. y Putative gene markers have been found recently, but further studies are needed before the gene mutation is characterized and the gene product is identified.
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