Radiological differential diagnoses of ALERD
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acute encephalopathy AND diffusion
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ALERD radiological differential diagnosis MRI acute encephalopathy biphasic seizures late reduced diffusion
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https://pmc.ncbi.nlm.nih.gov/articles/PMC6069315
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acute leukoencephalopathy restricted diffusion
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acute leukoencephalopathy restricted diffusion ALERD MRI diffusion weighted image pediatric
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ALERD (acute leukoencephalopathy with restricted diffusion) is a pediatric acute encephalopathy syndrome, typically after febrile infection and prolonged seizures. MRI often shows bilateral, fairly symmetric cortical and subcortical white-matter true diffusion restriction on DWI with low ADC, while early T2/FLAIR changes can be minor. Two patterns are described:
- Diffuse ALERD: widespread cortical-subcortical restriction, often severe.
- Central-sparing ALERD / AESD phenotype: frontal or frontoparietal subcortical restriction, with sparing around the Sylvian fissures, perirolandic cortex, and often deep gray nuclei. It can produce the “bright-tree appearance” on DWI. ALERD imaging review
Radiological differential diagnoses
| Differential | Imaging clues favoring the alternative over ALERD |
|---|---|
| AESD (acute encephalopathy with biphasic seizures and late reduced diffusion) | Often considered the central-sparing subtype within the ALERD spectrum rather than a wholly separate differential. DWI can be initially normal, then show subcortical frontal/frontoparietal restriction around days 3-9 after a second seizure cluster, with perirolandic and Sylvian-region sparing. |
| Hypoxic-ischemic encephalopathy (HIE) | Diffusion restriction predominantly affects vulnerable gray matter: perirolandic cortex, hippocampi, basal ganglia, thalami, and sometimes watershed cortex. A documented hypoxic event is typical. Relative sparing of perirolandic cortex and basal ganglia supports central-sparing ALERD/AESD. HIE MRI pattern |
| Arterial ischemic infarction | Lesions conform to a vascular territory, are usually asymmetric, and may show arterial occlusion or perfusion abnormality. ALERD is generally bilateral, non-territorial, and symmetric. |
| Cerebral venous sinus thrombosis / venous infarction | Hemorrhagic cortical-subcortical lesions, edema crossing arterial territories, and abnormal venous sinuses or cortical veins on MR venography. |
| Status epilepticus-related diffusion abnormality | Cortical ribboning, hippocampal, pulvinar, or peri-ictal changes often lateralize to seizure onset zone and can show hyperperfusion. ALERD has more extensive bilateral subcortical white-matter involvement and fits a febrile encephalopathy pattern. |
| Viral encephalitis | More focal, pathogen-specific tropism: temporal-insular and limbic involvement in HSV; thalamic involvement in some arboviral infections; rhombencephalitis in selected infections. Associated meningeal enhancement, hemorrhage, CSF pleocytosis, or focal necrosis favors encephalitis. |
| Acute disseminated encephalomyelitis (ADEM) | Multifocal, asymmetric, poorly marginated T2/FLAIR hyperintense lesions in deep/periventricular white matter, basal ganglia, brainstem, cerebellum, and spinal cord. Restriction is usually less striking or less extensive than ALERD; enhancement may occur. |
| Acute hemorrhagic leukoencephalitis (AHLE) | Fulminant, asymmetric or multifocal white-matter lesions with hemorrhage on SWI/GRE, marked edema/mass effect, and sometimes ring or patchy enhancement. Hemorrhage is not typical of ALERD. |
| Toxic leukoencephalopathy | Symmetric white-matter restriction may closely mimic ALERD. Distribution and exposure history are key: chemotherapy, methotrexate, metronidazole, immunosuppressants, inhaled heroin, carbon monoxide, or other toxins. The ALERD review specifically highlights toxic leukoencephalopathy as a close mimic. Review discussion |
| Metabolic encephalopathy | Pattern directs the diagnosis: hyperammonemia often involves insular/cingulate cortices; hypoglycemia may involve posterior cortex, hippocampi, and internal capsules; mitochondrial disease may show non-territorial cortical lesions with lactate peak on MRS. Check glucose, ammonia, lactate, liver/renal studies, and metabolic testing. |
| Osmotic demyelination syndrome | Central pontine lesion, with possible extrapontine basal-ganglia/thalamic involvement, after rapid correction of chronic hyponatremia or major osmotic shifts. Distribution and electrolyte history are distinctive. |
| Posterior reversible encephalopathy syndrome (PRES) | Vasogenic edema, predominantly parieto-occipital and subcortical, is bright on ADC rather than diffusely low. Restricted diffusion can occur in complicated PRES but is usually regional rather than the typical ALERD pattern. |
| MERS / CLOCC (reversible splenial lesion syndrome) | Isolated, oval midline splenial corpus-callosum restriction, sometimes with limited adjacent white-matter involvement. Diffuse cortical-subcortical restriction points instead toward ALERD. |
| Non-accidental injury / shaken infant syndrome | Subdural collections, retinal hemorrhage clinically, diffuse axonal injury, and hypoxic-ischemic pattern. Susceptibility imaging and skeletal survey assist when clinically indicated. |
| Inherited leukodystrophy or mitochondrial disorder | Usually pre-existing developmental concerns, chronic or recurrent imaging abnormalities, characteristic tract-based or regional white-matter patterns, and absence of the classic acute febrile encephalopathy course. |
Practical MRI discriminators
- Confirm true restriction: DWI hyperintensity must have low ADC, rather than shine-through.
- Distribution:
- Bilateral cortical-subcortical, non-territorial restriction: favors ALERD.
- Perirolandic cortex plus deep gray nuclei: favors HIE.
- Temporal-insular limbic pattern: consider HSV encephalitis.
- Isolated splenium: consider MERS/CLOCC.
- Hemorrhagic white matter: consider AHLE, venous infarction, trauma, or vasculitis.
- Timing matters: MRI may be normal in the first few days in ALERD/AESD. Delayed DWI abnormalities after a biphasic seizure course favor AESD/central-sparing ALERD. AESD timing and pattern
- Use the full protocol: DWI/ADC, FLAIR, SWI/GRE, post-contrast imaging when infection/inflammation is considered, MRA/MRV when vascular disease is possible, and MRS when metabolic disease is suspected.
- Correlate with CSF, metabolic tests, EEG, and exposure history. Imaging alone may not reliably separate ALERD from toxic, hypoxic, seizure-related, or infectious injury.
The literature describes lesion distribution and CSF findings as especially useful in separating ALERD from ischemia/infarction and encephalitis. ALERD review Recent systematic-review searching did not identify a relevant ALERD-specific meta-analysis that changes this imaging differential.
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