Sections

Pantothenate Kinase-Associated Neurodegeneration (PKAN)

Sections Pantothenate Kinase-Associated Neurodegeneration (PKAN)
Overview
Presentation
DDx
Workup
Treatment
Medication
References

Workup

Approach Considerations

No biochemical markers have been found in pantothenate kinase-associated neurodegeneration (PKAN). Levels of copper, ceruloplasmin, lipids, amino acids, and acanthocytes typically are measured in the blood to exclude other conditions. Radionuclide scan reveals increased iron uptake in the basal ganglia.^[23]

Cultured skin fibroblasts have been reported to accumulate iron (⁵⁹ Fe) transferrin, but the isotope is no longer available for human use.

Increased platelet monoamine oxidase ̶ B activity has been reported.^[24]Bone marrow histiocytes and peripheral lymphocytes may demonstrate the presence of abnormal cytosomes, including fingerprint, granular, and multilaminated bodies.^{[25, 26]}The characteristics of the material suggest the presence of ceroid lipofuscin.

CT scanning

Computed tomography (CT) imaging is not very helpful in the diagnosis of PKAN but may show hypodensity in the basal ganglia and some atrophy of the brain. Calcification in the basal ganglia in the absence of any atrophy also has been described.

SPECT scanning

Iodine-123 (¹²³ I)-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane (CIT) single-photon emission computed tomography (SPECT) scanning and (¹²³ I)-iodobenzamide (IBZM)-SPECT scanning also have been used in making the diagnosis of PKAN.^{[27, 28]}

MRI

MRI has increased the likelihood of antemortem diagnosis of PKAN.^{[29, 30, 31]}The image below depicts the typical MRI appearance in PKAN, revealing bilaterally symmetrical, hyperintense signal changes in the anterior medial globus pallidus, with surrounding hypointensity in the globus pallidus, on T2-weighted scanning. These imaging features are fairly diagnostic of PKAN and have been termed the "eye-of-the-tiger sign."^{[30, 31, 32, 33, 34]}

Magnetic resonance imaging (MRI) has increased the likelihood of antemortem diagnosis of Pantothenate kinase-associated neurodegeneration (PKAN). 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 PKAN, 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.

A study by McNeill et al concluded that in most cases of PKAN, different subtypes of neurodegeneration associated with brain iron accumulation can be reliably distinguished with T2 and T2, fast ̶ spin echo brain MRI.^[31]

Using a 7T MRI to quantify the amount of iron deposition, patients with PKAN were found to have a more than 3-fold higher concentration of iron in the globus pallidus, subthalamic nucleus and internal capsule, compared to normal controls. Patients heterozygous for the PANK2 mutation did not have any findings of iron deposition.^[35]

A recent study of 21 patients with PKAN compared to 21 age-matched controls, showed reductions of fractional anisotropy on diffusion tensor imaging mainly in the periventricular substance surrounding the third ventricle, the medial part of both putamina and in the frontal white matter including the anterior limbs of the internal capsules and the corpus callosum. In the infratentorial region, cerebellar white matter and dorsal parts of the pons and medulla were affected. This new finding indicates that cerebral tissue dysfunction is likely more widespread than previously thought.^[36]

Laboratory Studies

Molecular genetic testing used in PKAN and NBIA comprises testing for PANK2 through sequence or deletion/duplication analysis. When one pathogenic variant (sequence variant or partial- and whole-gene deletion) is identified in a person with an "eye of the tiger" sign on MRI, the diagnosis of PKAN is confirmed.^[37]

Treatment & Management

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Media Gallery

Magnetic resonance imaging (MRI) has increased the likelihood of antemortem diagnosis of Pantothenate kinase-associated neurodegeneration (PKAN). 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 PKAN, 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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Author

Philip A Hanna, MD Associate Professor of Neuroscience, JFK Neuroscience Institute at JFK Medical Center, Hackensack Meridian School of Medicine at Seton Hall University

Philip A Hanna, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, International Parkinson and Movement Disorder 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.

Esther Fischer Resident Physician, Department of Neurology, JFK Neuroscience Institute, JFK Medical Center, Hackensack Meridian School of Medicine at Seton Hall University

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 Morsani 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, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity (DigiTrace), Brain Sentinel, Cavion, Ceribell, Eisai, Greenwich, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion<br/>Serve(d) as a speaker or a member of a speakers bureau for: Bioserenity (DigiTrace), Brain Sentinel, Cavion, Ceribell, Eisai, Greenwich, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion<br/>Received research grant from: LivaNova, Greenwich, SK biopharmaceuticals, Takeda,.

Acknowledgements

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

Sections Pantothenate Kinase-Associated Neurodegeneration (PKAN)
Overview
Presentation
DDx
Workup
Treatment
Medication
References

Pantothenate Kinase-Associated Neurodegeneration (PKAN) Workup

Approach Considerations

CT Scanning and MRI

CT scanning

SPECT scanning

MRI

Laboratory Studies

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Pantothenate Kinase-Associated Neurodegeneration (PKAN) Workup

Approach Considerations

CT Scanning and MRI

CT scanning

SPECT scanning

MRI

Laboratory Studies

References

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