Pantothenate Kinase-Associated Neurodegeneration (PKAN) Treatment & Management

Updated: Dec 07, 2016
  • Author: Philip A Hanna, MD; Chief Editor: Selim R Benbadis, MD  more...
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Treatment

Approach Considerations

The treatment of patients with pantothenate kinase-associated neurodegeneration (PKAN) remains mostly symptomatic. The tremor responds best to dopaminergic agents. The anticholinergic agent benztropine may be used to help rigidity and tremor. Benzodiazepines have been tried for choreoathetotic movements.

Hypertonia is usually a combination of rigidity and spasticity and may be difficult to treat. Dopamine agonists and anticholinergics may help to reduce rigidity. Baclofen in moderate doses relieves the stiffness and spasms and can reduce dystonia. Intramuscular botulinum toxin has also been used. [37]

Symptoms such as drooling and dysarthria can be troublesome. Medications such as methscopolamine bromide can be tried for excessive drooling. Dysarthria may respond to medications used for rigidity and spasticity. Speech therapy also may be useful, and computer-assisted devices may be used in advanced cases. A gastrostomy feeding may be necessary as the dysphagia progresses.

A multidisciplinary team approach involving physical, occupational, and speech therapists may be needed in selected patients with a protracted course to improve functional skills and communication.

Systemic chelating agents, such as desferrioxamine, have been used in an attempt to remove excess iron from the brain, but these have not proved beneficial. Dementia is progressive, and no treatment has proved clearly effective.

In vitro, pluripotent stem cells derived from PKAN patients responded to the administration of coenzyme A by preventing neuronal death and reactive oxygen species formation. [42]

Inpatient care

Admission for supportive care is occasionally necessary.

Referrals

Referral to a neurologist, particularly a movement disorders specialist, is helpful. Rehabilitation physicians often are consulted to coordinate the different therapy regimens.

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Treatment of Dystonia

Dystonia is the most prominent and disabling symptom of PKAN and may respond modestly to dopaminergic agents such as levodopa and bromocriptine (a dopamine agonist). Other dopamine agonists, such as ropinirole or pramipexole, can also be considered, although no formal studies have been conducted on their efficacy in PKAN.

Anticholinergics, such as trihexyphenidyl, may be used when dopaminergic agents are not helpful. However, these medications bring only transient relief for dystonia, and physical therapy is often of limited benefit as well. Botulinum toxin can be injected into severely affected muscles to relieve dystonia.

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Medical Care

High-dose pantothenate, the PANK2 enzyme substrate, has anecdotally been shown to improve symptoms such as dysarthria, gait imbalance, and sense of well being. Since pantothenate has no known toxicity in humans, even in high doses (</= 10 g/day) some individuals, particularly with atypical disease, have used it as a dietary supplement. [37]

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Surgical Care

Because dystonia is a prominent feature of PKAN, the globus pallidus has been a target for surgical treatment. Stereotactic pallidotomy and bilateral thalamotomy have occasionally been tried in patients with severe dystonia, resulting in partial relief of symptoms. [33] Deep brain stimulation of the globus pallidus has been used in these patients with promising results. [34, 35]

In 2005, six individuals with PKAN underwent DBS. At follow-up, 6 to 48 months later, they all showed improvements in writing, speech, walking, and global measures of motor skills. In addition, a multicenter retrospective study of 23 patients from 16 centers, the majority of whom had PKAN, were tracked for 15 months post DBS. Overall, patients reported improvement in dystonia and quality of life. Patients with the most severe dystonia seemed to be the ones who benefited most from DBS. [37]

Continuous intrathecal baclofen infusion has been tried for refractory, generalized dystonia without much success. An alternative is intraventricular baclofen, of interest because this site may deliver benefit in patients who have primarily upper-body and facial dystonia, such as blepharospasm. [37]

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Diet

Diet may play a role in the treatment of PKAN. A case study performed on a set of twins with PKAN indicated a positive response to a hypercaloric diet. The twins were placed on a diet of 50 kcal/kg for 2 weeks, and both were noted to have improvement particularly with regards to dystonia of the neck and trunk, as well as with gait and strength of hand grip. [41]

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