Sections

Pantothenate Kinase-Associated Neurodegeneration (PKAN)

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

Presentation

History

Symptoms in pantothenate kinase-associated neurodegeneration (PKAN) include the following:

Dystonia - A prominent and early feature
Significant speech disturbances - Can occur early
Dysphagia - A common symptom; caused by rigidity and corticobulbar involvement
Dementia - Present in most individuals with PKAN
Visual impairment - Caused by optic atrophy or retinal degeneration; not uncommon and can be the presenting symptom of the disease, although this is rare
Seizures - Have been described^[18]

Clinical manifestations of PKAN vary from patient to patient. The symptoms usually begin in the first decade with a motor disorder of extrapyramidal type and gait difficulty. Extrapyramidal symptoms dominate the clinical picture and include rigidity, slowness of movement, dystonia, choreoathetosis, and tremor.

In patients with atypical PKAN, extrapyramidal dysfunction may be delayed for several years, and spasticity and dysarthria may be the presenting symptoms.

Physical Examination

Physical examination reveals signs consistent with extrapyramidal and corticospinal dysfunction. In addition to rigidity, dystonia, and chorea, patients may exhibit spasticity, brisk reflexes, and extensor plantar responses.

Based on the common clinical features, the following diagnostic criteria for PKAN have been proposed.^[18]For a definitive diagnosis, all of the obligate findings and at least 2 of the corroborative findings should be present. None of the exclusionary factors should be present.

Obligate features of PKAN include the following:

Onset during the first 2 decades of life
Progression of signs and symptoms
Evidence of extrapyramidal dysfunction, including 1 or more of the following: dystonia, rigidity, choreoathetosis

Corroborative features include the following:

Corticospinal tract involvement
Progressive intellectual impairment
Retinitis pigmentosa and/or optic atrophy
Seizures
Positive family history consistent with autosomal recessive inheritance
Hypointense areas on magnetic resonance imaging (MRI) involving the basal ganglia
Abnormal cytosomes in circulating lymphocytes and/or sea-blue histiocytes in bone marrow

Exclusionary features include the following:

Abnormal ceruloplasmin levels and/or abnormalities in copper metabolism
Presence of overt neuronal ceroid lipofuscinosis, as demonstrated by severe visual impairment and/or seizures that are difficult to control
Predominant epileptic symptoms
Severe retinal degeneration or visual impairment preceding other symptoms
Presence of familial history of Huntington chorea and/or other autosomal, dominantly inherited neuromovement disorders
Presence of caudate atrophy on imaging studies
Deficiency of hexosaminidase A
Deficiency of ganglioside monosialic acid-1 (GM1)–galactosidase
Nonprogressive course
Absence of extrapyramidal signs

Patients with atypical PKAN show more varied clinical features, with slower progression. Presenting symptoms usually involve speech defects, such as palilalia (repetition of words or phrases), tachylalia/tachylogia (rapid speech), and dysarthria (poor articulation, slurring). Motor involvement is usually a later feature. Onset is in the first three decades (mean age 13.6 years).^[22]

Differential Diagnoses

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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

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, MD Resident Physician, Department of Neurology, JFK Neuroscience Institute, JFK Medical Center, Hackensack Meridian School of Medicine

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, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

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) Clinical Presentation

History

Physical Examination

References

Tables

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