Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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March 11, 2021
Pantothenate Kinase-Associated Neurodegeneration (PKAN)
- Background:
- Most common form of neurodegeneration with brain iron accumulation (NBIA); prevalence of 1–3 per 1,000,000
- Autosomal recessive mutation of PANK2 gene → disrupts pantothenate kinase biochemical pathway
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Results in iron accumulation in the globi pallidi, progressing to diffuse brain atrophy
- Clinical Presentation:
- Action-induced jaw dystonia with eating/speaking and truncal opisthotonos are both highly suggestive.
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Classic PKAN (the majority):
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Early onset (<6 years) with rapid progression
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Limb dystonia, spasticity and clumsiness with falls, retinopathy (later); also developmental delay, ADHD, or toe walking
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Atypical PKAN:
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Older age of onset (13–14 years), with slower progression
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Neuropsychiatric or speech disturbance; later development of dystonia, parkinsonism, ADHD
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- Key Diagnostic Features:
- Early MRI may be normal or show only isolated high signal in the globi pallidi on T2WI.
- Classic T2WI: Symmetric hypointensity (due to increased iron) in the globi pallidi; central area of hyperintensity (due to gliosis and vacuolization); linear central stripe of T2 hyperintensity is the "eye of the tiger" sign, which is strongly associated with PANK2 mutation.
- Increased susceptibility on SWI/T2*WI due to iron accumulation in these regions
- MRS may show reduced NAA/increased myoinositol.
- Differential Diagnoses:
- Non-PANK2 NBIA: Typically homogeneous reduced signal on T2WI throughout the globi pallidi, without central hyperintensity
- Leigh syndrome: Symmetric hyperintensity on T2WI in the globi pallidi without surrounding low signal; frequently other areas of basal ganglia affected
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Wilson disease: More extensive areas of high signal involving the entire basal ganglia and ventrolateral thalamus on T2WI
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Toxic/metabolic (eg, cyanide/carbon monoxide poisoning): Bilateral, symmetric hyperintensity of the globi pallidi + relevant clinical history
- Treatment:
- There is currently no disease-modifying therapy for PKAN. Iron chelating agents (eg, deferiprone), while reducing brain iron levels, have not shown clinical trial success.
- Treatment is primarily symptomatic and includes antispasticity agents such as trihexyphenidyl, clonazepam, and baclofen. Pantothenate (vitamin B5) is a substrate in the PK pathway and may offer some clinical improvement.
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Thalamotomy and pallidotomy have been performed for disabling dystonia as well as deep brain stimulation, with mixed results and often not long-term success.
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