Table 3.

Differential diagnosis of Krabbe disease.

Disorder	Clinical features	Supratentorial white matter	Infratentorial white matter	Deep grey matter	Cerebral and cerebellar volume loss	Others/Comments
Early onset Krabbe disease	Relentlessly progressive spasticity, visual and hearing loss, seizures, decerebrate rigidity, unexplained hyperpyrexia	Periventricular and deep white matter with subcortical sparing, tigroid pattern	Pyramidal tracts Cerebellar white matter and dentate hilum typically involved	Thalamic hypointensity is typical	Marked cerebral volume loss	CT hyperdensity of thalamus Optic nerve hypertrophy Cranial nerve enhancement usually seen
Metachromatic leukodystrophy	Progressive motor and cognitive regression, sensory-motor demyelinating neuropathy, visual and hearing loss, seizures	Periventricular and deep white matter with subcortical sparing, tigroid pattern, Frontal predominance in late-onset	Pyramidal tracts Cerebellar white matter in some	Thalamic hypointensity may be seen	Less pronounced	CT hyperdensity is absent Enhancement of cranial nerves and spinal roots may be seen
Peroxisome Biogenesis Disorders	Dysmorphic facies, hypotonia, psychomotor retardation, hepatomegaly, sensorineural hearing loss, pigmentary retinopathy	Variable, commonly corticospinal tracts and posterior deep white matter, callosal splenium	Deep cerebellar white matter and dentate hilum	Absent	Can be present	Cortical malformations can be associated Some patterns can mimic adult-onset Krabbe as well
Hypomyelination of early myelinating structures	Normal neonatal period and early development followed by developmental stagnation, nystagmus, spasticity, and cerebellar ataxia	Trilaminar or tram-track PLIC, Periventricular and parietal white matter/optic radiations	Absent/mild peridentate white matter hyperintensity Hyperintensity of pons, medulla	Absent	Absent
ITPA mutation related early infantile epileptic encephalopathy	Progressive microcephaly, refractory seizures with onset in early infancy, profound developmental disability, cataract, cardiac conduction defects	T2 hyperintensity and restricted diffusion of PLIC Delayed myelination Variable restricted diffusion of optic radiations	Variable pyramidal tracts in the midbrain, middle and inferior cerebellar peduncles, dentate hilum and cerebellar white matter hyperintensity and restricted diffusion	Absent	Progressive cerebral atrophy	Serial MRIs may show less conspicuous T2 and DWI signal changes of PLIC
Neuronal ceroid lipofuscinosis	Visual loss due to maculopathy, regression of motor and intellectual functions, myoclonic seizures, ataxia and spasticity	Mild long TR hyperintensity of white matter, PLIC involvement is late except in LI variant	Usually spared	Marked thalamic T2 hypointensity and volume loss in later stages	Pronounced volume loss Cerebellar >Cerebral in LI variant
Mitochondrial disorders	Heterogeneous group with recurrent encephalopathy, ataxia, spasticity, seizures, neuropathy, visual loss, cardiac and liver involvement	Confluent deep white matter hyperintensity with or without restricted diffusion	Variably involved	Basal ganglia and thalamus can be involved depending on the specific gene involved	Can be present	Significant Restricted diffusion is usually present and is a distinguishing feature
Krabbe disease later onset	Progressive spastic hemiparesis or quadriparesis, progressive visual loss, ataxia, neuropathy and cognitive decline	Posterior periventricular, splenial and CST involvement No zonal pattern or enhancement	Absent	Absent	Absent	No enhancement diffusion restriction can be seen
Adrenoleukodystrophy/adrenomyeloneuropathy (AMN)	Progressive visual and hearing loss, cognitive decline with behavioral disturbances, spasticity, and ataxia. AMN presents in third-fourth decade with slowly progressive spasticity, neuropathy, bladder and bowel incontinence	Posterior periventricular and splenial with CST involvement Zonal pattern with enhancement and restricted diffusion of leading edge	Absent	Absent	Absent
ALS	Progressive asymmetric muscle weakness of limbs, fasciculations, UMN signs, bulbar weakness, and breathlessness	Isolated corticospinal tract involvement with milder T2 hyperintensity	CST	Absent	Absent	T2 hyperintensity is usually milder than seen in Krabbe disease

PLIC: Posterior limb of internal capsule, CST: Corticospinal tract, MRI: Magnetic resonance imaging, DWI: Diffusion-weighted imaging, LI: Late-infantile