Hallervorden-Spatz Disease Differential Diagnoses

  • Author: Philip A Hanna, MD; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Feb 28, 2012
 
 

Diagnostic Considerations

The differential diagnosis of Hallervorden-Spatz disease (HSD) includes other diseases presenting with extrapyramidal-pyramidal-dementia complex.

Wilson disease

Wilson disease usually presents with tremors, rigidity, dementia, and pseudobulbar features and has an autosomal recessive mode of inheritance. Slit-lamp examination of the eyes may reveal a Kayser-Fleischer ring. MRI in Wilson disease exhibits the characteristic changes consisting of high-intensity lesions in the basal ganglia, thalami, and mid brain on T2-weighted images. The normal low intensity of red nuclei and SN surrounded by abnormal high-signal intensity in the tegmentum of the mid brain gives rise to the typical "face-of-the-giant-panda" sign. Results from serum ceruloplasmin and copper studies are usually abnormal and help to confirm the diagnosis. Neurologic symptoms are reversible if treated early with copper chelation therapy; hence, an early diagnosis is important.

Juvenile form of Huntington disease

The juvenile form of Huntington disease may be confused with HSD. Patients with this form of Huntington disease present with a predominantly akinetic-rigid syndrome (ie, Westphal variant). The differentiating features include an autosomal dominant mode of inheritance and the presence of caudate atrophy on MRI.

Juvenile neuronal ceroid lipofuscinosis

Juvenile neuronal ceroid lipofuscinosis may be difficult to distinguish from HSD. It is an inherited disorder characterized by storage of ceroid and lipofuscin in neuronal and other tissues. The symptoms start in early childhood with vision loss, retinitis pigmentosa, dementia, rigidity, and dystonia. In contrast to the infantile and late-infantile forms of the disease, generalized tonic-clonic seizures and myoclonic seizures are not very common.

The diagnosis can be made on the basis of clinical presentation, electrophysiologic studies, and skin biopsy findings. The electroretinogram reveals markedly reduced amplitude, and visual and somatosensory evoked responses are increased. The characteristic fingerprint inclusion bodies are identified easily in eccrine sweat glands and in circulating lymphocytes.

Machado-Joseph disease

Machado-Joseph disease is inherited as an autosomal dominant trait, and the onset of clinical disease is usually later, after age 20 years. Ataxia and other signs of spinocerebellar dysfunction are predominant. Some affected children may have extrapyramidal features, but prominent ataxia and the inheritance pattern help to differentiate Machado-Joseph disease from HSD.

Neuroacanthocytosis

Neuroacanthocytosis is characterized by onset in the third or fourth decade and prominent orofacial dyskinesia, chorea, dystonia, and cognitive changes. Other features include self-mutilation, peripheral neuropathy, and seizures. Recognition of acanthocytes (red blood cells with irregular spine on the cell surface) in the peripheral smear can lead to the diagnosis.

HARP syndrome, which is characterized by hypoprebetalipoproteinemia, acanthocytes, retinitis pigmentosa, and pallidal degeneration, is another form of neuroacanthocytosis. It presents clinically with dyskinesias, dystonia, and progressive dementia. The lipoprotein electrophoresis reveals the absence of the prebeta fraction, and MRI exhibits hypointense signals in the globus pallidus.

GM gangliosidoses

Rare metabolic disorders such as GM1 and GM2 gangliosidoses in children sometimes can have features similar to HSD, but they have other clinical features and lab abnormalities and are differentiated readily.

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Philip A Hanna, MD  Associate Professor, Department of Neuroscience, Seton Hall University School of Graduate Medical Education; Residency Program Director, New Jersey Neuroscience Institute, JFK Medical Center; Neurology Director, Huntington's Disease Unit, JFK Hartwyck-Cedarbrook

Philip A Hanna, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Movement Disorders Society

Disclosure: Nothing to disclose.

Coauthor(s)

Neeta Garg, MD, DM  Assistant Professor, Department of Neurology, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Neeta Garg, MD, DM is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Additional Contributors

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Brian L Gerhardstein, MD, PhD Staff Physician, Department of Neurology, New Jersey Neuroscience Institute, JFK Medical Center

Disclosure: Nothing to disclose.

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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Magnetic resonance imaging (MRI) has increased the likelihood of antemortem diagnosis of Hallervorden-Spatz (HSD) disease. The typical MRI findings include bilaterally symmetrical, hyperintense signal changes in the anterior medial globus pallidus, with surrounding hypointensity in the globus pallidus, on T2-weighted images. These imaging features, which are fairly diagnostic of HSD, have been termed the "eye-of-the-tiger sign." The hyperintensity represents pathologic changes, including gliosis, demyelination, neuronal loss, and axonal swelling. The surrounding hypointensity is due to loss of signal secondary to iron deposition.
 
 
 
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