Pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN), previouslyhistorically also 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:

• progressive dementia
• extrapyramidal signs (rigidity, dystonia, choreoathetosis)
• corticospinal signs (spasticity, hyper-reflexiahyperreflexia)
• dysarthria
• retinitis pigmentosa
• tremors

The clinical course is usually relentlessly progressive with affected individuals dying in their second or third decade.

Radiographic features

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

MRI

• T2: T2-weighted MRI images often demonstrate hypointense changes in the globiglobus pallidi and pars reticulata of the 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 vacualisationvacuolisation ³.

MR spectroscopy

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

History and etymology

ItThe condition was previously named after two 20^4th:

• century German neuropathologists Julius Hallervorden (1882-1965): Neuropathologist and, Germany
• his superior, Hugo Spatz(1888-1969): Anatomist, Munich, Germany

Both Hugo Spatz and Julius Hallervorden were involved inpersonally examined 697 brains from disabled adults and children who had been murdered as part of the Nazi euthanasia program and, as such,at the alternativeKaiser-Wilhelm-Institut für Hirnforschung in Berlin-Buch. Hugo Spatz,was Director of his division. Thus the alternate name isof the condition - pantothenate kinase-associated neurodegeneration - is now preferred by somecontemporaneous authors. Brief biographical entries on Spatz and Hallervorden make an interesting reading ¹¹³.