IMAGING OF DEMYELINATING DISEASES

Dr. Sunil Kumar SharmaSenior ResidentDept. of NeurologyGMC Kota

Introduction

Demyelinating diseases comprise of diseases of central and peripheral nervous system in which disruption of myelin is a dominant feature.

Diseases affecting central nervous system (CNS) myelin can be classified on the basis of whether a primary biochemical abnormality of myelin exists(dysmyelinating) or whether some other process damages the myelin or oligodendroglial cells (demyelinating).

Cell BodyDendritesAxonsPresynaptic terminals Bundles of axons form nerves

Cell BodyContains the nucleusDendritesReceptive regions; transmit impulse to cell bodyShort, often highly branchedMay be modified to form receptorsAxonsTransmit impulses away from cell bodyAxon hillock; trigger zoneWhere action potentials first developPresynaptic terminals (terminal boutons)Contain neurotransmitter substance (NT)Release of NT stimulates impulse in next neuronBundles of axons form nerves

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Myelin sheath Gray matter primarily contains neurons and their processes & the white matter is composed predominantly of myelinated bundles of axons

The oligodendroglial cell membrane is the source of the myelin sheath, which is a tightly wrapped, multilayered membrane which ensheathes axons

Myelin sheath

Cholesterol, galactocerebroside, sphingomyelin, and phospholipids are the lipids found in fully formed white matter and account for the stability and strength .

Transmission electron micrograph of a myelinated axon, myelin sheath, which is a tightly wrapped, multilayered membrane

Classification of diseases of myelin

Acute disseminated encephalomyelitis (ADEM)

Best diagnostic clue: Multifocal WM/basal ganglia lesions 7-14 days following infection/vaccination

Location: May involve both brain and spinal cord; predominantly WM but also gray matter (GM)

MRI Findings

T2WI: T2 abnormalities better seen with FLAIRFLAIRMultifocal punctate to large flocculent FLAIR hyperintensitiesBilateral but asymmetric Involve peripheral WM/GM junctionCan involve brain stem and posterior fossa Do not usually involve callososeptal interfaceTumefactive, mass-like lesions possible, yet with less mass effect than expected for size

ADEMDWI

Variably restricted diffusion in acute lesions

Apparent diffusion coefficient (ADC): Increased In ADEM Due to extracellular water within demyelination

T1 C+Punctate, ring, incomplete ring, peripheral enhancementCranial nerve(s) may enhanceMRSN-acetylaspartate (NAA) low within regions of prolonged T2Other metabolites usually normal

Best imaging tool-Contrast-enhanced MRI

Acute disseminated encephalomyelitis. A: SagittalT2-weighted image demonstrates high signal intensity of the majority of the spinal cord with mild expansion in the cervicothoracic region.

B: Axial T2-weighted image of the cervical cord demonstrates involvement of both gray and white matter.

Inflammatory Demyelinating Pseudotumor

Clinical Features- Demyelinating diseases occasionally present as solitary, focal, or ill-defined space-occupying lesions in the brain that closely mimic a neoplasm both clinically and radiologically.

These lesions can be found in all age groups but mostly in the third to fifth decades .

The clinical features are similar to those of postinfectious/postvaccinal encephalomyelitis, i.e. an acute onset of symptoms and dramatic response to steroids.

In contrast to classic MS, there is no predilection for the periventricular white matter, optic nerves, or brainstem.

If the diagnosis of demyelination is considered, biopsy can perhaps be delayed and patients can be imaged after treatment with steroids to look for regression of MR findings

Inflammatory demyelinating pseudotumor-Axial FLAIR images demonstrate ill-defined high signal intensity within the right frontoparietal white matter (A) and effacement of adjacent gyri and extension along the length of the corticospinal tract, (B) the posterior limb of the internal capsule, and (C) the cerebral peduncle. Postcontrast axial T1-weighted image (D) shows ill-defined minimal enhancement. These findings mimic the appearance of a large infiltrative neoplasm. Biopsy confirmed the presence of demyelination.

Multiple sclerosis (MS)MR FindingsTlWIAcute: Iso-/mildly hypointenseChronic: Hypointense center, hyperintense rimVariable atrophy; mostly loss of WM

T2WIHigh convexity "sand-like( < 2 mm diameter) Virchow-Robin spaces in recent-onset MSHypointense basal ganglia 10-20% chronic MS

Multiple sclerosis (MS)FLAIRBilateral, asymmetric linear/ovoid FLAIR hyperintensities

Perivenular extension; "Dawson finger Along path of deep medullary veins

Hyperintensities become confluent with severityDWIAcute lesions-Concentric ring pattern on diffusion-weighted images with hyperintense rim

MSTl C+Transient enhancement during active demyelination (> 90% disappear within 6 months)

Nodular (68%)

Ring (23%)

Semilunar, incomplete, "horseshoe-shaped" (9%)

MSMRS NAA (NAA/Cr), Choline (Cho/Cr)

MRS abnormalities found in NAWM

Only secondary progressive MS shows NAA in normal appearing gray matter (NAGM)

May allow early distinction between relapsing-remitting & secondary-progressive

MR diagnosis of MS requires 3 discrete lesions 5 mmLesions in characteristic locationMS compatible clinical history

Nuclear Medicine FindingsPET: Glucose utilization correlates with NAA in lesions and NAWM

Imaging RecommendationsBest imaging tool: MRIProtocol advice: Contrast-enhanced MR with sagittal FLAIR

Extensive cervical spinal cord lesions with multiple sclerosis. A: Sagittal T2-weighted image shows extensive irregular high signal within the cord substance. B: Axial T2-weighted image shows the typical peripheral location of the multiple sclerosis plaque.

C: A patient with multiple sclerosis shows an ill-defined lesion on T2-weighted image extending from the dorsal medulla to C2. D: Postcontrast T1-weighted image demonstrates minimal peripheral enhancement.

Differential Diagnoses for MSADEMViral prodrome, monophasic illnessAssymetricalCC not involved

Autoimmune-mediated VasculitisEnhancing lesions spare callososeptal interface"Beaded" angiogram appearance

Lyme diseaseCan be identical to MS (skin rash common)Susac syndromeClinical presentation, course different from MSClassic triad of Encephalopathy ,Branch retinal artery occlusions & Hearing loss.Self-limited (2-4 y duration, then stabilizes),MonophasicMultifocal supratentorial WM lesionsAlways involves CC

DDs. Of MS

Acute hemorrhagic leukoencephalitis (Hurst disease)

Acute hemorrhagic leukoencephalitis (Hurst disease) is considered a hyperacute or fulminant form of ADEM This entity is typically seen in young

Patients have an abrupt onset of fever, neck stiffness, and progressive neurologic deficits often leading to coma and death within 1 to 5 days.

Acute hemorrhagic leukoencephalitis (Hurst disease)reported after viral respiratory infections, sepsis, ulcerative colitis and asthma, and as a manifestation of drug toxicity .

CSF -elevation of IgG and the presence of MBP.

clinical recovery are reported after the administration of high-dose steroids

Acute hemorrhagic leukoencephalitis (Hurst disease)

Extensive abnormal signal involving the supraventricular white matter is present, with acute hemorrhage present as foci of marked hypointensity within the white matter lesions.

PMLPML is caused by reactivation of a latent infection by a papovavirus (JC virus).

Most cases of PML today occur as a complication of AIDS, and approx. 5% of all patients with AIDS ultimately develop PML

The non-AIDS population typically harbors an underlying disease affecting immunocompetence, such as leukemia, lymphoma, sarcoidosis, tuberculosis, or malignancy, or has received immunosuppressive therapy

PML

HIV encephalopathy

HIV encephalopathy, also known as AIDS dementia complex, HIV dementia, and hiv-associated dementia complex is a progressive dementing illness of AIDS.

Occurs in patients with advanced immunosuppression.

The most common finding on imaging is atrophy of the brain.

HIV encephalopathyIn early stages of the disease, small areas of high signal intensity are seen on the t2-weighted sequences in the periventricular white matter that lack mass effect or edema

Bilateral symmetric increased signal intensity on the T2-weighted sequences has been described in the basal ganglia (caudate and putamen) and thalamus and may also involve the brainstem

Human immunodeficiency virus encephalopathy in a patient with acquired immunodeficiency syndrome showing diffuse white matter involvement. AD: FLAIR images progressing inferiorly to superiorly demonstrate diffuse white matter signal abnormality.

Human immunodeficiency virus encephalopathy with characteristic involvement of the basal ganglia. A: Axial FLAIR image demonstrates bilateral symmetric increased signal intensity within the basal ganglia and external capsules. B: Axial postcontrast T1-weighted image demonstrates no evidence of enhancement.

Neuromyelitis Optica Neuromyelitis optica (Devic type) is a syndrome of acute onset of optic neuritis and transverse myelitis (LETM) that develop at approximately the same time

Classically, NMO patients have relapses consisting of optic neuritis and myelitis

The target of the NMO antibody is the Aquaporin-4 (AQP4).

Central Pontine and Extrapontine Myelinolysis (Osmotic Demyelination)

Central pontine myelinolysis describes demyelination usually isolated to the central pons; however, extrapontine sites of demyelination are not uncommon.

It is commonly found in association with alcoholism, chronic nutritional deficiency, and many other systemic disorders with electrolyte abnormalities including chronic pulmonary disease, liver and kidney diseases, diabetes mellitus, liver transplant, and neoplasia.

The term osmotic demyelination syndrome has been proposed because of the common association with rapidly corrected hyponatremia.

The symptoms of central pontine myelinolysis include spastic quadriparesis, pseudobulbar palsy, changing levels of consciousness, and coma .

A significant proportion of patients progress to death, which may be preceded by a state of pseudocoma (locked-in syndrome).

Central pontine myelinolysis. A: T2-weighted axial image shows characteristic high signal intensity within the midpons, with a surrounding rim of normal-appearing pontine parenchyma and sparing of the corticospinal tracts. B: Sagittal T1-weighted image demonstrates a low-signal lesion within the pons.

Marchiafava-Bignami Disease

Marchiafava-Bignami disease is a rare condition in which demyelination and necrosis primarily affect the corpus callosum and sometimes also involve extracallosal regions.

It is almost exclusively found in male alcoholics and was originally described in Italian people who drank red wine .

In more recent years, it has been described in poorly nourished nondrinkers

Marchiafava-Bignami Disease

Sagittal T1-weighted image (A) demonstrates small areas of low signal intensity in the genu, body, and splenium of the CC

Subacute Combined Degeneration of the Spinal Cord

Vitamin B12 (cobalamin) deficiency may affect the CNS or peripheral nervous system but most commonly involves the spinal cord.

Subacute combined degeneration (SCD) refers to vitamin B12 deficiency with demyelination and vacuolation found in the posterior and lateral columns of the spinal cord

Subacute combined degeneration of the spinal cord (B12 deficiency). A: Sagittal T2-weighted image demonstrates a long segment of high signal intensity within the dorsal aspect of the cervical spinal cord. B: Axial T2-weighted image shows high signal intensity within the dorsal columns.

Hypertensive Encephalopathy (Reversible Posterior Leukoencephalopathy)

Hypertensive encephalopathy is a clinical entity that it is important to recognize early because the clinical and imaging findings are usually reversible.Acute elevation of blood pressure (several hours to days before the onset of symptoms) is the most common precipitantThe syndrome can also be seen with renal decompensation, preeclampsia/eclampsia, fluid retention, and treatment with immunosuppressive drugs .Cyclosporine ,tacrolimus, FK506, L-asparaginase, cisplatin, and mouse monoclonal antibody (OKT3)

Thank You

References

Magnetic Resonance Imaging of the Brain and Spine, 4th ed, 2009, Scott W. Atlas

Bradley ; neurology in clinical practice 7th edition

Osborn Diagnostic Imaging Brain 2004