Pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN), previously known as Hallervorden-Spatz syndrome, is an autosomal recessive disorder causing involuntary spasticity and progressive dementia. It is a subset of neurodegeneration with brain iron accumulation (NBIA).

Epidemiology

Classical PKAN tends to have onset before 6 years of age, whereas atypical PKAN manifests at a mean age of 14 years ¹⁰. Prevalence is estimated around 1-3 per million ¹⁰.

Clinical presentation

Described features include ^9,11:

• rigidityprogressive dementia
• extrapyramidal signs (rigidity, dystonia, choreoathetosis)
• corticospinal signs (spasticity, hyper-reflexia)
• dysarthria
• dystonia
• retinitis pigmentosa
• progressive mental retardation
• cognitive impairment 
• spasticity
• tremors

Radiographic features

Reflects areas of iron deposition, mainly globi pallidi, substantia nigra, and red nuclei.

MRI

• T2: T2-weighted MRI images often demonstrate hypointense changes in globi pallidi and pars reticulata of substantia nigra
• SWI/T2*: shows susceptibility artefact (low signal) in corresponding areas from iron deposition ⁷

Cortex is usually spared but caudate atrophy may be seen in more advanced cases. The "eye of the tiger" sign refers to a central T2 relatively hyperintense spot (line) within the hypointense globi pallidi due to gliosis and vacualisation ³.

MR spectroscopy

• shows decreased NAA peak due to neuronal loss and may show increased myoinositol ⁸ 

History and etymology

It was previously named after ⁴:

• Julius Hallervorden (1882-1965): Neuropathologist, Germany
• Hugo Spatz (1888-1969): Anatomist, Munich, Germany

Both Hugo Spatz and Julius Hallervorden were involved in the Nazi euthanasia program and, as such, the alternative name is preferred by some authors. Brief biographical entries on Spatz and Hallervorden make an interesting reading ¹.