Sections

Pantothenate Kinase-Associated Neurodegeneration (PKAN)

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

Medication

Medication Summary

As previously mentioned, dopaminergic agents, such as levodopa and bromocriptine, can produce modest improvements in dystonia. If dopaminergic agents are not effective against dystonia, anticholinergics can be used, but they offer only transient relief. Botulinum toxin injections also can improve dystonic muscles.

Agents used to relieve rigidity and spasticity may prove effective against dysarthria, while methscopolamine bromide can deter excessive drooling.

Class Summary

These agents reduce morbidity associated with dopamine deficiency.

Levodopa/carbidopa (Sinemet, Sinemet CR, Parcopa)

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Carbidopa (a decarboxylase inhibitor) is administered with levodopa to prevent the breakdown of levodopa and increase levodopa's bioavailability. Thus, carbidopa decreases the need for large doses of levodopa to achieve adequate brain dopamine levels. The levodopa/carbidopa combination is often used when symptom control with selegiline alone is insufficient. The CR levodopa/carbidopa formulation can help to prevent the on/off phenomenon in some patients.

The Sinemet tablet is available in a 4:1 ratio (Sinemet 100/25) and a 10:1 ratio (Sinemet 100/10 and 250/25) of levodopa to carbidopa. The Sinemet CR tablet contains a 4:1 ratio of levodopa to carbidopa (100/25 or 200/50); the daily dosage of Sinemet CR must be determined by careful titration.

Bromocriptine (Parlodel, Cycloset)

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Bromocriptine is a semisynthetic ergot alkaloid derivative. It is a strong dopamine D2-receptor agonist and a partial dopamine D1-receptor agonist. Bromocriptine may relieve akinesia, rigidity, and tremor associated with Parkinson disease. It stimulates dopamine receptors in the corpus striatum. It is, however, less effective than other dopamine agonists. It can be used as an adjunct to levodopa/carbidopa.

Approximately 28% of the drug is absorbed from the gastrointestinal (GI) tract and metabolized in the liver. The approximate elimination half-life is 50 hours, with 85% of bromocriptine excreted in feces and 3-6% eliminated in urine. The drug is initiated at a low dose with slow titration; increase in the dose every 2 weeks. If severe adverse reactions occur, the dose is reduced in 2.5-mg decrements.

Class Summary

These agents are thought to act centrally by suppressing the conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.

Trihexyphenidyl

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This is a centrally acting anticholinergic agent that tends to diminish the muscle spasms.

Benztropine (Cogentin)

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By blocking the striatal cholinergic receptors, benztropine may help in balancing the cholinergic and the dopaminergic activity in the striatum.

Scopolamine (Transderm Scop Patch, Scopace)

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Scopolamine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system (CNS). It antagonizes the action of histamine and serotonin.

Class Summary

By binding to the specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Clonazepam (Klonopin)

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Clonazepam suppresses the muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.

Class Summary

These agents produce symptomatic improvement in muscle strength by relieving spasticity and autonomic symptoms, or both in some patients.

Botulinum toxin type A (BOTOX)

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This agent binds to the receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which, in turn, inhibits the transmission of impulses at the neuromuscular junction.

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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) Medication

Medication Summary

Antiparkinson Agents, Dopamine Agonists

Class Summary

Levodopa/carbidopa (Sinemet, Sinemet CR, Parcopa)