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KEY FACTS

Terminology
- Wallerian degeneration (WaD)
- Progressive secondary anterograde degeneration of axons and their myelin sheaths caused by interruption of axonal integrity or damage to neuron
Imaging
- Primary lesion is cortical or subcortical with WaD in descending white matter (WM) tracts ipsilateral to neuronal injury - WaD can be seen in fibers crossing corpus callosum, fibers of optic radiations, fornices, and cerebellar peduncles
- CT is not sensitive for WaD in acute-subacute stages - Detects atrophy of corticospinal tracts (CSTs) in chronic stage
- Time-dependent changes in CSTs on MR - Strong correlation between WaD detected on T2WI and DWI and long-term morbidity - DWI findings precede development of WaD assessed by conventional MR
- DTI may distinguish between primary lesion and associated WaD - Reduced fractional anisotropy (FA) with ↑ mean diffusivity (MD) in infarct - Reduced FA with preserved MD in CST
Top Differential Diagnoses
- Normal CST can appear T2/FLAIR hyperintense on high-field-strength MR
- Neurodegenerative diseases
- Brainstem glioma
- Demyelinating and inflammatory diseases
- Hypertrophic olivary degeneration
- Metabolic diseases
- Intoxication (heroin inhalation)

TERMINOLOGY

Abbreviations
- Wallerian degeneration (WaD)
Definitions
- Progressive secondary anterograde degeneration of axons and their myelin sheaths caused by interruption of axonal integrity or damage to neuron

IMAGING

General Features

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, corticopontocerebellar tracts
        - Corpus callosum, posterior column of spinal cord, limbic circuit, and optic pathway
- 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 WaD of commissural nerve fibers of neocortex
        - Callosal atrophy is present predominantly in latest stage of Alzheimer disease
- Seizure-induced damage may cause secondary WM degeneration along tapetum and through splenium of corpus callosum

Size

- Acute stage: Normal size
- Chronic stage: ↓ (atrophy)

Morphology

- Signal changes conforming to WM tract shape
        - Oval regions in posterior limb of IC and cerebral peduncle; thin curvilinear regions in pons

CT Findings

NECT

- Not sensitive for WaD in acute-subacute stages
- Detects atrophy of CSTs in chronic stage
        - ↓ size of corresponding aspect of brainstem

MR Findings

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

FLAIR
```
- Same as T2WI
```

DWI

- Can demonstrate acute injury to descending WM tracts < 10 days after primary injury such as infarction
- 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

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 ↑ 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

Imaging Recommendations

Best imaging tool
```
- MR
```

Protocol advice

- DWI allows early detection (stage 1)
- T2WI detects changes after 4 weeks

DIFFERENTIAL DIAGNOSIS

Normal CST
- CST can appear T2/FLAIR hyperintense on 3T MR (normal fully myelinated brain)
Neurodegenerative Diseases
- Amyotrophic lateral sclerosis (upper &/or lower motor neuron involvement) - Bilateral hyperintensities along CST extending from corona radiata to brainstem on T2WI/PD/FLAIR
- Primary lateral sclerosis and infantile-onset hereditary spastic paraplegia - Upper motor neuron degeneration only
Brainstem Glioma
- T2 hyperintense mass ± enhancement
Demyelinating and Inflammatory Diseases
Hypertrophic Olivary Degeneration
- Secondary degeneration of inferior olivary nucleus (ION), usually caused by primary lesions in dentato-rubro-olivary pathway
- Time-dependent T2 changes of ION - Hyperintense signal without hypertrophy of ION: Within first 6 months of ictus - Both ↑ signal and hypertrophy of ION: Between 6 months and 3-4 years after ictus - Only ↑ signal in ION: Begins when hypertrophy resolves and can persist indefinitely
Metabolic Diseases
Heroin Inhalation
- Symmetric T2 hyperintensity in posterior WM, including posterior limb of IC

PATHOLOGY

General Features

Etiology

- Infarction, hemorrhage, neoplasm, encephalitis
- Demyelinating disease, trauma, arteriovenous malformations
- Reported also in patients with movement disorder

Genetics

- Process of axonal degeneration is genetically regulated

Associated abnormalities

- Primary lesion/disorder that caused secondary WM tract degeneration

Staging, Grading, & Classification
- Stage 1 (0-4 weeks) - Degradation of axon; mild changes in myelin
- Stage 2 (4-14 weeks) - Myelin protein breakdown; lipids remain intact
- Stage 3 (> 14 weeks) - Myelin lipid breakdown, gliosis, changes in water content and structure
- Stage 4 (after months to years) - Atrophy of ipsilateral brainstem
Gross Pathologic & Surgical Features
- Brainstem asymmetry due to atrophy in chronic stage
Microscopic Features
- Stage 1: Beginning of myelin and axon breakdown - Myelin sheaths break up into ellipsoids and spheres but retain myelin-staining properties
- Stage 2: ↓ protein:lipid ratio
- Stage 3: ↑ edema and further lipid breakdown
- Stage 4: Atrophy due to volume loss; removal of axonal debris by microglia continues for 2 years (vs. completed in 3 weeks in peripheral nervous system)
- Expression of transcription factors ATF3 and JUN by nonneuronal cells during WaD - ATF3/JUN heterodimers may play role in regulating changes in gene expression necessary for preparing distal segments of injured peripheral nerves for axonal regeneration - Absence of ATF3 and JUN from CNS glia during WaD may limit their ability to support regeneration
- In CNS, astrocyte-dominated matrix fails to accommodate new axonal growth

CLINICAL ISSUES

Presentation

Most common signs/symptoms

- WaD in CST is associated with persistent hemiparesis

Demographics

Age
```
- Reported in all ages
```
Sex
```
- No preference
```

Epidemiology

- WaD commonly follows CNS lesions
        - WaD in pyramidal tract reported in 78.6% of cases of capsular infarct

Natural History & Prognosis
- WaD may begin within 1 week of fiber tract damage
- Demyelination can continue during next 6 months
- Signifies irreversible loss of neuronal function - Little evidence of axonal regeneration in CNS
- Presence or absence of WaD may influence clinical outcome after stroke
- Extent of WaD is related to severity of motor deficit - Abnormal DWI signal in CST can be acute predictor of motor outcome in childhood infarction - Contralesional CST abnormal DWI signal predicts severe hemiparesis
Treatment
- No specific therapy

DIAGNOSTIC CHECKLIST

Image Interpretation Pearls
- In ischemic stroke: Important to differentiate DWI abnormality related to WaD from additional infarction
- Time-specific signal intensity changes of WaD → able to ascertain age of primary lesion

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References

Selected References

Images

Selected Images

Coronal T2WI shows a cavernous malformation in left precentral gyrus . T2 hyperintensity along the course of cortical spinal tract (CST) indicating antegrade wallerian degeneration (WaD).

Axial NECT shows changes of a remote right-sided craniotomy with right frontotemporal encephalomalacia and atrophy of right cerebral peduncle due to antegrade WaD. Also note ex vacuo dilation of right lateral ventricle .

Axial DWI in a patient with recent infarcts in the left occipital lobe and left internal capsule show restricted diffusion restriction along splenium , indicating WaD.

Left pontine remote infarct with WaD of bilateral middle cerebellar peduncles (MCPs) is shown. Axial FLAIR (A) shows left pontine small remote infarct . Axial FLAIR (B) & diffusion weighted image (C) show hyperintense signal in MCPs due to WaD.

Axial ADC map in a newborn with acute infarcts in bilateral frontal and right occipital lobes shows decreased ADC signal in the genu and splenium of the corpus callosum due to acute WaD.

Axial T2WI in the same patient shows increased T2 signal in bilateral frontal and right occipital lobes corresponding to acute infarcts. Subtle hyperintense signal in genu & splenium is difficult to assess due to high water content in the neonatal brain.

Coronal T2WI in a 6-year-old boy with left-sided spasticity and history of perinatal insult shows periventricular cystic encephalomalacia with ex vacuo dilation of the right lateral ventricle.

$Axial DTI in the same patient shows decreased fractional anisotropy in the right pontine corticospinal tract due to WaD. Note intact CST on the contralateral side .$ Axial DTI in the same patient shows decreased fractional anisotropy in the right pontine corticospinal tract due to WaD. Note intact CST on the contralateral side .

Axial FLAIR MR at the corona radiata level in a 65 year old with bilateral (left > > right) corona radiata infiltrative low-grade glioma and WaD of cerebral peduncles shows white matter (WM) hyperintense signal due to an infiltrative glioma .

Axial FLAIR image in the same patient shows mild atrophy and hyperintense signal in bilateral cerebral peduncles . Considering atrophy of cerebral peduncles, WaD was considered more likely than tumor extension.

Additional Images

Axial T2WI MR in a patient with left middle cerebral artery infarct (not shown) shows high signal intensity in the left cerebral peduncle , consistent with WaD.

Axial T2WI MR shows a large left middle cerebral artery infarct, which resulted in ipsilateral WaD (not shown).

Axial T2WI MR in the same patient illustrates the hyperintense signal within the left cerebral peduncle from WaD.

Axial T2WI MR in the same patient shows hyperintense signal in crossing CSTs in the left side of the pons , consistent with WaD.

Axial T2WI MR in the same patient shows hyperintense signal in the right side of the medulla , consistent with WaD.

Axial T2WI MR in a patient with a left middle cerebral artery infarct shows no abnormal signal in the pons, although diffusion revealed abnormality from WaD (not shown).

Anisotropy map in which high anisotropy values are seen in red shows diminished anisotropy in the left side of the pons despite normal T2WI in the same patient.

$Axial DTI trace image shows increased signal in the left corona radiata/CST related to an acute infarct . DTI may distinguish between the primary lesion and associated WaD. Reduced fractional anisotropy may be seen in the affected CST.$ Axial DTI trace image shows increased signal in the left corona radiata/CST related to an acute infarct . DTI may distinguish between the primary lesion and associated WaD. Reduced fractional anisotropy may be seen in the affected CST.

Axial DTI trace shows increased signal in the central cerebral peduncle related to CST WaD. The lateral cerebral peduncle may show corticopontine tract involvement.

Axial T2WI MR shows a heterogeneous hyperintense lesion involving the left corona radiata and CST related to a glioblastoma. Note the internal curvilinear T2 hypointensity related to blood products or proteinaceous debris.

Axial T2WI MR in the same patient shows cerebral peduncle hyperintensity due to CST WaD from the tumor. There is slight volume loss with linear T2 hypointensity along the posterolateral margin .

31 KiB Raw Blame History

KEY FACTS

Terminology

Imaging

Top Differential Diagnoses

TERMINOLOGY

Abbreviations

Definitions

IMAGING

General Features

Best diagnostic clue

Location

Size

Morphology

CT Findings

NECT

MR Findings

T1WI

T2WI

FLAIR

DWI

T1WI C+

MRS

Imaging Recommendations

Best imaging tool

Protocol advice

DIFFERENTIAL DIAGNOSIS

Normal CST

Neurodegenerative Diseases

Demyelinating and Inflammatory Diseases

Metabolic Diseases

PATHOLOGY

General Features

Etiology

Genetics

Associated abnormalities

Staging, Grading, & Classification

Gross Pathologic & Surgical Features

Microscopic Features

CLINICAL ISSUES

Presentation

Most common signs/symptoms

Demographics

Age

Sex

Epidemiology

Natural History & Prognosis

Treatment

DIAGNOSTIC CHECKLIST

Image Interpretation Pearls

References

Selected References

Images

Selected Images

Additional Images

31 KiB

Raw Blame History