Wallerian Degeneration

Wallerian degeneration (WaD)

Secondary anterograde degeneration of axons and their myelin sheaths caused by interruption of the axonal integrity or damage to the neuron

Best diagnostic clue

• Contiguous T2 hyperintensity along topographic distribution of corticospinal tract (CST) in internal capsule (IC) and brainstem in patients with various cerebral pathologies

Location

• Primary lesion: Cortical or subcortical

• WaD: Descending white matter (WM) tracts ipsilateral to neuronal injury

  • –

    CST, corticobulbar, corticopontine tracts

  • –

    Optic radiations

• Center of cerebral peduncle may reveal WaD of CST

• Lateral side of cerebral peduncle may show WaD of corticopontine tract

• WaD can be seen in corpus callosum, optic radiations, fornices, and cerebellar peduncles

  • –

    WaD in distal optic radiations after infarction at their root

  • –

    Pontine infarct can cause WaD in middle cerebellar peduncle

• Corpus callosum has been shown to be susceptible to atrophy in Alzheimer disease mainly as correlate of wallerian degeneration of commissural nerve fibers of neocortex

  • –

    Callosal atrophy is present predominantly in latest stage of Alzheimer disease

    • □

      2 mechanisms contribute to WM alterations: WaD in posterior subregions and myelin breakdown process in anterior subregions

• Seizure-induced damage may cause secondary white matter degeneration along tapetum and through splenium of corpus callosum

Size

• Acute stage: Normal size

• Chronic stage: Decreased (atrophy)

Morphology

• Signal changes conforming to WM tract shape

  • –

    Oval regions in posterior limb of IC and cerebral peduncle; thin curvilinear regions in pons

NECT

• Not sensitive for WaD in acute-subacute stages

• Detects atrophy of CSTs in chronic stage

  • –

    ↓ size of corresponding aspect of brainstem

T1WI

• Time-dependent changes in descending WM tracts

  • –

    Stage 1: No changes

  • –

    Stage 2: T1 hyperintense

  • –

    Stage 3: T1 hypointense

  • –

    Stage 4: Ipsilateral brainstem atrophy ± hypointensity

T2WI

• Time-dependent changes in descending WM tracts

  • –

    Stage 1: No changes in adult CNS

  • –

    Stage 2: T2 hypointense

  • –

    Stage 3: T2 hyperintense

  • –

    Stage 4: Atrophy, best seen in brainstem

    • □

      Sometimes, T2 hyperintense signal may persist

• Neonates and infants: Identification of WaD by T2WI complicated by high water content and lack of myelination in immature WM

• Adults: Strong correlation between T2WI detected WaD and long-term morbidity

PD/intermediate

• High intensity follows particular WM pathway

FLAIR

• Same as T2WI

DWI

• Neonates and infants: Indicates acute WM injury

  • –

    DWI findings precede development of WaD assessed by conventional MR

  • –

    May portend poor clinical outcome

• Adults: Correlation of DW changes in descending motor pathways at presentation with long-term neurologic disability

• ↑ signal intensity in descending WM tract ipsilateral to territorial infarct at level of IC or cerebral peduncle or both

• ↓ ADC values in involved WM tract compared with normal WM

• Extent and severity of territorial ischemia is related to development of descending WM tract injury detectable by DWI

• Hyperintense DW signal intensity and ↓ ADC values within territorial infarct and ipsilateral CST

  • –

    DW and ADC time courses in region of territorial injury and CST injury may be different

    • □

      Relatively delayed development of diffusion abnormality in descending WM tracts

• Subacute period after territorial infarction in adults

  • –

    Within infarct, WM ADC reduction > that in GM

• DW signal intensity abnormality in descending WM tracts may persist, even as DW hyperintensity in ipsilateral cerebral hemisphere fades

• WaD of inferior cerebellar peduncle (after lateral medullary infarction) depicted by thin slice DWI has been reported

T1WI C+

• No contrast enhancement of degenerated tracts

MRS

• ¹H-MRS enables in vivo assessment of axonal injury based on signal intensity of N-acetyl aspartate (NAA)

• ↓ NAA concentration in normal-appearing WM in pons and cerebellar peduncles in early stages of relapsing-remitting multiple sclerosis (MS)

  • –

    Evidence of early WaD outside MS plaques

  • –

    Correlates best with disability, MS duration, and relapse rate

Diffusion tensor imaging (DTI)

• Myelin breakdown leads to ↓ diffusion anisotropy

• DTI may distinguish between primary lesion and associated WaD

  • –

    Difference in diffusion properties between primary lesion and degenerated tract

    • □

      Fractional anisotropy (FA) = measure of directionality of water diffusion

    • □

      Mean diffusivity (MD) = measure of amount of water diffusion

• Reduced FA with increased mean diffusivity (MD) in infarct

• Reduced FA with preserved MD in CST

• In patients with motor pathway infarction, diffusion indices in degenerated CST stabilize within 3 months and early changes in CST FA may predict long-term clinical outcomes