Multiple Sclerosis : Diagnosis & Differential Diagnosis

Dr.Ram Raut JR III (Medicine)BJMC & SGH Pune

Epidemiology

• The most common progressive neurologic disease of young adults.

• Risk Factors: – Female sex, young age– White race– Northern latitude (USA)– High socioeconomic status– Scandinavian ancestry– Month of birth effect– Vitamin D deficiency

Diagnosis of Multiple sclerosis

• No single test to diagnose multiple sclerosis.

• Diagnosis relies on recognition of clinical patterns of the disease as well as exclusion of possible mimics.

• Waxing & waning neurological deficit is the hall mark of disease.

• Supported by MRI studies, CSF & Evoked potential studies.

REQUIREMENTS FOR DIAGNOSIS

• Clinically definite MS requires 2 or more episodes of symptoms & 2 or more signs that reflect pathology in anatomically non-contagious white matter tracts of the CNS.

• Symptoms must last >24 h &• Occur as distinct episodes separated by a month or more

• At least 1 of the 2 signs must be present on neurological examination &• Other may be documented by abnormal paraclinical tests (MRI, VEPs)

• Second clinical event may be supported solely by paraclinical information, usually the development of new focal white matter lesions on MRI.

• If there is gradual progression of disability > 6 months, & no superimposed relapses, documentation of Intrathecal IgG synthesis may be used.

Clinical Features of Multiple Sclerosis SYMPTOM PERCENTAGE SYMPTOM PERCENTAGE

Sensory disturbance 34 Facial weakness 1

Weakness 22 Dysarthria 0.6

Visual loss 13 Hearing loss 0.6

Ataxia 11 Cramps 0.6

Diplopia 8 Loss of consciousness 0.6

Vertigo 4.3 Psychiatric symptoms 0.3

Fatigue 2 Poor memory 0.3

Facial pain 2 Dysphagia 0.3

Headache 2 Loss of taste 0.3

Bladder dysfunction 1

1) Heat sensitivity e.g. Uhthoff’s symptom

2) Lhermitte’s symptom

3) Paroxysmal symptoms e.g. paroxysmal tonic seizures, Dysarthria, sensory symptoms.

4) Trigeminal neuralgia (tic douloereux), hemifacial spasm, gloosopharyngeal neuralgia.

5) Facial myokymia

Ancillary Symptoms of Multiple Sclerosis

Clinical course of Multiple Sclerosis

Natural History Of Multiple Sclerosis

Clinically Isolated Syndrome

• The first demyelinating event that is suggestive of MS is called CIS.

• Typical course – 60-85% cases of RRMS will eventually progress to

SPMS .The median time is 10 yrs .

• Benign MS –

• Acute Fulminant MS (Marburg variant)

Differentiating point RRMS PPMS

Incidence 85% 10%

Symptoms at Onset

Variable Typically asymmetric weakness /gait disturbance

Visual loss common Rare

Female preponderance Equal

30 yrs 40 yrs

Rate of progress slow 50% faster than RRMS

Disease burden Fewer than RRMS & SPMS

Salient Features of PPMS vs RRMS

KURTZKE’S EDSS

DIAGNOSTIC TESTS

MRI Evoked potentials

CSF

MRI in MS• Characteristic abnormalities found in >95 % .

• Although sensitive , not specific (many D/Ds for same lesions)

• To study evolution of existing lesions & occurrence of new lesions.

• Detection of subclinical activity.

• DIS- Simultaneous presence of asymptomatic Gd enhancing & other non enhancing lesions.

• To evaluate response to treatment.

Brain MRI in MS

• Leakage of IV Gd in parenchyma - Marker of inflammation.

• Plaques - as hyper intense lesion on T2 & proton density images, & FLAIR images. - signifies demyelination

• 1/3rd of the T2 lesions are hypo intense on T1 (Black Holes)

- signifies irreversible axonal loss

T2-weighted (A) and post-contrast T1-weighted (B) MR images. In A, many white-matter lesions . Two of them enhanced in B with gadolinium-DTPA. This is a sign of increased blood–bran barrier permeability and continuing inflammation.

• On Gadolinium contrast- acute plaques show contrast enhancement .

- Homogenous or ring pattern & Persist for 3 weeks

• On sagittal view ,lesions are linear or flame like streaks perpendicular to the ventricular surfaces… s/o perivenous demyelination (Dawson’s fingers).

• Brain atrophy greater than expected for the age.

• Wallerian Degeneration (rare)

Brain MRI in MS

• Site- Multifocal lesions -

1) WML (corpus Callosum, brainstem, cerebellum), 2) GML ( thalami, Basal ganglia), 3) cortical lesions (type 1,2,3).

• Size- Larger than 6 mm, round /ovoid having “fuzzy borders”.

• Burden of the disease Total volume of T2 weighted signal abnormalities &/or

atrophy.

MRI lesions of MS in Brain

Spinal cord MRI in MS

• Plaques can be seen in the parenchyma of the cord on T2 /Gd enhanced T1 imaging.

• Typically oriented longitudinally along the cord, often posteriorly, spanning 2-3 segments.

• Focal cord swelling may be present

Diagnosis: Imaging

FLAIR T2 T1 T1 Post C FLAIR

1) Periventricular-lateral/temporal horns2) Corpus Callosum/ Callosal-Septal

Interface

Cortex, and Deep Gray Matter are Rare at 5% at 1.5T; although at 7T in most patients gray matter/cortical lesions will be visible. Majority of lesions do not enhance.

3) Sub cortical (best seen on FLAIR)4) Optic Nerves/Visual Pathways5) Brain stem/Cerebellar Peduncles

Characteristic locations of MS lesions on MRI Brain

Newer MRI techniques

• MTR (magnetization transfer ratio) imaging- able to distinguish demyelination from edema.

• Proton magnetic resonance spectroscopic imaging (MRSI)- quantitate molecules like N-acetyl aspartate a marker of axonal integrity.

Evoked potentials

• Afferent (visual, auditory, somatosensory) or efferent (motor) CNS pathways.

• Computer averaging to measure CNS electric potentials evoked by selected peripheral nerves or of the brain.

• Provide most information when pathways studied are clinically uninvolved.

• Abnormalities occur in 75-90%.

• Not specific but marked asymmetric delay in latency of a specific EP component is s/o demyelination.

EVOKED POTENTIALS

• VER (visual evoked response) -75% abnormal regardless of optic neuritis.

• BAER (brainstem auditory evoked response)

- 30% abnormal

• SSER (somatosensory evoked response)

- 80% abnormal Helps distinguish peripheral from

central lesions

• Asymmetric delay of the P-100 potential & conduction block (when acute ON)

• Delays or block of 1) N-20 potential of

median nerve 2) p37 potential of

tibial nerve

Characteristic findings in MS

CSF in MS

• Abnormal in 85-90 % cases of MS.

• Mononuclear cell pleocytosis (>5 & <50 cells)

• Increased levels of intrathecally synthesized IgG

• Total CSF protein Normal

• CSF IgG index = (Ratio of CSF IgG to albumin)/(ratio of serum IgG to albumin)

• Oligoclonal banding (OCB) by agarose gel electrophoresis.

• Paired serum samples studied to exclude Non CNS origin of any OCBs in CSF.

Intrathecal synthesis of IgG can occur in other conditions like syphilis, SSPE, Viral encephalitis, & Lyme disease.

Clinical Attacks Lesions Additional criteria for Diagnosis

2 or more

Objective clinical evidence of ≥ 2 lesions or objective clinical evidence of 1 lesion with reasonable historical evidence of a prior attack

None. Clinical evidence alone will suffice, additional evidence desirable but must be consistent with MS

2 or more Objective clinical evidence of 1 lesion DIS ; OR await further clinical attack implicating a different CNS site

1 Objective clinical evidence of ≥2 lesions DIT ; OR await a second clinical attack.

1 Objective clinical evidence of 1 lesion DIS ; OR await further clinical attack implicating a different CNS site AND DIT ; OR await a second clinical attack

0 (progressio

n from onset)

One year of disease progression (retrospective or prospective) AND at least 2 of the following 3 : DIS in brain based on ≥ 1 T2 lesion in periventricular, juxtacortical or infratentorial region ;DIS in the spinal cord based on ≥ 2 T2 lesions; or positive CSF (e/o OCB and/or elevated IgG index)

2010 Revised McDonald MS Diagnostic Criteria Diagnosis of MS requires elimination of more likely diagnoses

& demonstration of Dissemination of lesions in space ( in space ( DIS) and time (DIT)

PARA CLINICAL EVIDENCE IN MS DIAGNOSIS

EVIDENCE FOR DISSEMINATION OF LESIONS IN SPACE (DIS)

≥ 1 T2 lesion in at least 2 of 4 areas of CNS (periventricular, juxtacortical, infratentorial, spinal cord.

• Gd enhancement not required for DIS

• If brainstem or spinal cord syndrome, the symptomatic lesions are excluded & do not contribute to the lesion count.

EVIDENCE FOR DISSEMINATION OF LESIONS IN TIME (DIT)

•A new T2 &/or Gd enhancing lesion(s) on f/u MRI with ref to a baseline scan irrespective of the timing of baseline MRI or

•Simultaneous presence of asymptomatic Gd enhancing & non enhancing lesions at any time

Evidence for Positive CSF Oligoclonal IgG bands in CSF ( & not serum) or Elevated IgG index

These criteria are developed thru the consensus of the inter national panel on the diagnosis of MS

Differential Diagnosis Of Multiple sclerosis

• Acute disseminated encephalomyelitis (ADEM)

• Antiphospholipid antibody syndrome• Behcet’s disease• Cerebral autosomal dominant

arteriopathy, sub cortical infarcts, & leucoencephalopathy (CADASIL)

• Congenital leucodystrophies (adrenoleucodystrophy, metachromatic leucodystrophy)

• HIV infection• Ischemic optic neuropathy (arteritic &

non arteritic)• Lyme disease• Mitochondrial encephalopathy with lactic

acidosis & stroke (MELAS)

• Neoplasms (lymphoma, glioma, meningioma)

• Sarcoid• Sjogren’s syndrome• Stroke & ischemic cerebrovascular

diseases• Syphillis• SLE & related collagen vascular

diseases• Tropical spastic paraparesis (HTLV

I/II infection)• Vascular malformations (especially

spinal dural AV fistulas)• Vasculitis (Primary CNS or other)• Vitamin B12 deficiency

• Fever• Concomitant systemic disease.• Dermatologic involvement other than psoriasis• Endocrine disease other than autoimmune thyroid disease• Mucosal ulcerations• Sicca • Bone lesions• Tendon Xanthomas• Hematologic manifestations• Systemic thrombosis• Recurrent spontaneous abortions• Onset after 50 yrs of age

When to consider alternative diagnosis

• Peripheral neuropathy• Myopathy• Hearing loss• Multiple cranial neuropathy• Neuropsychiatric illness other

than unipolar depression• Prominent cognitive symptoms

from onset• CVST/Cortical & lacunar infarcts• Extrapyramidal features• Amyotrophy

Neurologic features that warrant further diagnostic considerations

•Meningismus/ meningeal enhancement on imaging

•Unilateral lesions

•Myelopathy alone

•Normal brain MRI

•Retinopathy

•CNS hemorrhage•Simultaneous enhancement of all lesions

MS Variants1) Marburg variant (Acute MS)

2) Balo’s Concentric Sclerosis

3) Disseminated subpial demyelination

4) Schilder’s Disease – A rare progressive demyelinating disorder (Myelinoclastic

diffuse sclerosis) which usually begins in childhood. It is not same as Addison-Schilder disease (adrenoleucodystrophy).

5) Mass Lesion

6) Neuromyelitis Optica (Devic Syndrome)

7) Opticospinal MS

8) Tumefactive MS

NEUROMYELITIS OPTICA (NMO)

NMO (Devic’s syndrome) -An aggressive inflammatory disorder

of acute ON & myelitis.

• Attacks of ON can be bilateral (unilateral in MS)• Myelitis can be severe & transverse (rare in MS) & typically longitudinally

extensive involving 3 or more contagious vertebral segments

• Lesions - Hypothalamus, periaqueductal brainstem, or ‘cloud like WML’ in cerebral hemispheres are suggestive of NMO.

• Spinal cord MRI – focal enhancing region of swelling & cavitation extending over 3 or more spinal cord segments & often in central gray matter.

• Up to 40 % have systemic autoimmune disorder. Other causes are infection, para neoplastic or idiopathic.

• Aquaporin-4 auto-antibody against water channel protein is present in 60 -70%

Progressive Myelopathy• Typically presents as asymmetric progressive Myelopathy with insidious

onset.

• Onset usually older than RRMS

• M:f= 1:1

• CSF analysis is essential for diagnosis. But 10-15 % will not have increased IT IgG.

• D/Ds – neoplasm, AV malformations, B12 def, Sarcoid, Sjogren's, HSP, Syphillis, HIV, HTLV.

• Esp. Dural AVM in old people having progressive Myelopathy.

• Accordingly Invx include- MRI Spine, B12 levels, MMA, Homocystine, Sr.ACE levels, RF, VLFA, Anti-SSA & B, ANA, VDRL, FTPA, HIV & HTLV .

Progressive cognitive impairment with symmetric white matter disease.

• In adults, leucodystrophies often present with progressive cognitive impairment.

• WML similar to MS are seen on imaging .

• But these are more confluent & symmetric. (focal plaques in MS)

• D/Ds- adrenoleucodystrophy, Metachromatic leucodystrophy, Krabbe’s disease, MTHFR def, Biotinidase def, CADASIL.

• Some leucodystrophies are associated with peripheral neuropathy.

• NCV with nerve biopsy can narrow the diagnostic considerations.

Cranial neuropathies• Ms can affect cranial nerves like optic nerve & can cause facial paresis.

• Similar features are seen in Behcet’s, Sjogren’s, skull base infiltrating tumors, TB, Sarcoidosis.

• Behcet’s syndrome – Cranial neuropathies, oro-genital ulcerations, dermatographia, elevated ESR.

• Sjogren’s syndrome- sicca syndrome, confirmed by biopsy of minor salivary or lacrimal gland.

• MRI/ CT are useful in skull base infiltrating tumors.

• CSF analysis, cytology, PCR, & culture can identify neoplastic cells or mycobacterium.

Acute transverse myelitis (ATM)• Spinal cord inflammation resulting in

motor & sphincter impairment with neurological level.

• Usually bilateral & tends to be more severe.

• Causes – HZV, HSV, collagen vascular diseases, sarcoidosis & idiopathic.

• ATM can be a presenting feature of NMO.

• Anti NMO IgG antibody should be checked if there is longitudinally extensive myelitis

Spinal Imaging - To exclude compressive etiology, tumors & AVM.

Brain imaging - Look for disseminated demyelination.

CSF analysis & blood studies- For e/o systemic inflammation & infection.

Infarcts of anterior spinal artery, may be distinguished by preserved dorsal column signs & CSF analysis (no leucocytosis & no IT IgG synthesis.

The Mimics

Patients may have radiologic findings consistent with MS But have symptoms that are not.

Another distinguishing feature of MS mimickers is that standard MS treatments often fail.

Acute disseminated Encephalomyelitis (ADEM)

• Monophasic illness. Rapid onset.• Multifocal inflammation & demyelination.• Children>adults• Altered sensorium & seizures are common.(rare in MS)• MRI - Multiple lesions often contrast enhancing (acute)• CSF- Lymphocytic pleocytosis, protein elevation, IT IgG

Post infectious – Measles, chickenpox, mumps, mononucleosis, influenza, parainfluenza, rubella, mycoplasma.

Post vaccination.-Rabies, smallpox.

Autoimmune response to MBP (Molecular mimicry)

Hurst disease- Type of ADEM with acute Fulminant hemorrhagic leucoencephalitis.

Causes

Inflammatory

Acute Disseminated Encephalomyelitis

ADEM is characterized by supratentorial and infratentorial deep white matter lesions with poorly defined margins and periventricular sparing. Bilateral gray nuclei lesions in the basal ganglia and thalamus.

Diffuse thoracic spinal cord lesions will be over 2 segments long. More likely to enhance and be peripheral not periventricular. Differentiation of MS from ADEM is more likely if 2 of 3 criteria are met; absent diffuse bilateral lesion pattern, presence of black holes, and 2 or more periventricular lesions.

T2FLAIRFLAIR T2

Neuromyelitis Optica

FLAIR T2 T1 Post CFLAIRFLAIR

Linear lesions can be found in the medulla and the spinal cord (spanning at least three vertebral segments and frequently causing cord expansion).

Where MS lesions contain a central vein and a hypo-intense rim, NMO lesions are frequently observed in the deep white matter, brainstem, and adjacent to the third and fourth ventricles . Optical coherence tomography reveals more nerve fiber damage than in MS, and cortical lesions are uncommon in NMO.

Inflammatory

Behcet’s

Lesions are commonly found in the brainstem, white matter (periventricular and superficial), internal capsule, basal ganglia, and thalamus.

Brain atrophy as well as changes in lesion shape and size, and 7% have enhancing lesions makes differentiation from MS difficult, to add the course can be monophasic, polyphasic or progressive.

Brainstem atrophy may predict a progressive course in neuro-Behcet’s. Lesions in the spinal cord (spanning multiple segments in the cervical or thoracic spine) are rare.

FLAIR T2FLAIR T1 Post C

Inflammatory

Sarcoid

Multiple hyper intense intraparachymal lesions.

Many cases will display chronic basilar leptomeningitis a finding not seen in MS,

Enhancement along the Virchow-Robin spaces appears linear. Hydrocephalus is a common finding.

Leptomeningeal enhancement along the third cranial nerve, and spinal nerve roots. Enhancement of the lacrimal gland (indicated by the arrow).

T1 Post CT1 Post CT1 Post CT1 Post CT1 Post C

Inflammatory

• Susac syndrome is a microangiopathy (Retinocochleocerebral Vasculopathy).• Characterized by encephalopathy, branch retinal artery occlusions & hearing loss.

T1 Post C FLAIR FLAIR

Small white matter lesions are observed on MRI.

Lesions like “black holes” of MS, but have a more prominent hypo intensity on T1.

T2 hyper intense lesions are seen in central corpus Callosum and the deep gray matter.

Parenchymal and leptomeningeal enhancement (not seen in MS).

Diffusion tensor imaging shows fiber tract loss. Cortical atrophy also has been observed.

Susac's syndrome

Systemic Lupus Erythematosus

Focal & punctate hyper-intensities in white and/or gray matter are indicative of vasculitis.

Unlike MS, white matter lesions in vasculitis are less periventricular & more peripheral .

MRA can show occlusions leading to abnormal blood flow.

Perfusion images, particularly MTT studies, can be more sensitive.

White matter hyper-intensities are more common if neuropsychiatric symptoms present.

T2 FLAIR MRA/MRV MTT

Inflammatory

Chronic Inflammatory Demyelinating Polyneuropathy

FLAIRFLAIR T1 Post C

Schwann cell proliferation causes peripheral nerve enlargement (onion bulb).

Hypertrophic spinal nerves can be detected on MRI.

Inflammatory

Demyelinating disease similar to standard MS, in which demyelinated tissues form concentric layers.

T2 T2 T2*

Concentric rings are seen on T2 imaging.

T1 Gadolinium enhancing rings are visible in areas of increased BBB permeability.

Micro hemorrhages and ectatic veins can be observed on 7T SWI.

Balos Concentric Sclerosis: A MS Variant

HIV's entrance into the brain causes CNS inflammation via cytokine release. The virus attacks oligodendrocytes, causing demyelination. Chronic inflammation results in changes such as gliosis and myelin pallor. CD4+ count can be correlated to the lesion patterns on MRI, such as gray and white matter loss and increases in venticular and sulcal CSF. Coinfection with Hepatitis C is also believed to play a role in white matter lesions. Gliosis and inflammation lead to cognitive impairment and eventually dementia. The blood brain barrier prevents the passage of medications, making treatment difficult.

Human Immunodeficiency Virus

•Periventricular white matter lesions can be observed on T2 images. Atrophy is a predominant finding. Despite HAART, atrophy & inflammatory changes can progress. •HIV patients also exhibit DTI abnormalities like in MS . •Basal ganglia involvement is more in HIV than MS. •The axial spine image shows enhancement in the corticospinal tracts bilaterally.• Diffuse white matter T2 signal abnormality (myelin pallor), often seen in PLHIV.

T2 T2T2 T2

Infectious

Progressive Multifocal Leucoencephalopathy

FLAIR T2

White matter hyper intensities observed particularly in FLAIR and T2 sequences.

T2 imaging shows increased signal radiating away from the ventricles along with corpus Callosum like MS, or can be more of a T2 pallor like in HIV .

Hypo intense lesions on T1 images are similar to “black holes” seen in MS.

Sub cortical U fibers are also affected in PML but cortical ribbon and gray matter are spared.

Infectious

The tickborne spirochete, Borrelia burgdorfera, causes Lyme disease. Patients present with a range of non-specific symptoms (headache, fatigue, myalgia). Patients may also present with multiple episodes of neurological deficits. The classic hallmark of Lyme disease is erythema migrans. Although 10-15% of patients have some sort of CNS involvement, the disease rarely affects the spinal cord. Antibiotic treatment is highly effective. Increased total protein, pleocytosis, and Bb (Borrelia burgdorfera) antibodies are present in CSF. The hallmarks of neuroborreliosis are meningitis, cranial neuritis and radiculoneuritis. Facial palsy is also common. Patients may also present with optic neuritis.

Neuroborreliosis (Lyme)

FLAIR T1 Post C T1 Post C

DWI and FLAIR imaging will show ischemic lesions.

MRA or Trans-cranial Doppler will show vasculitis changes and TIA-like lesions.

Meningeal and cranial nerve III enhancement are seen .

Infectious

Toxoplasmosis is the common CNS infection in AIDS patients. Almost half of HIV patients infected with the parasite will eventually develop toxoplasmosis. Approximately 20% - 70% of the American population is seropositive for Toxoplasma gondii. Patients present with headache and focal neurological deficits.

Toxoplasmosis

FLAIRFLAIR FLAIRT2

Multifocal hyper intense lesions in the white matter on T2 imaging.

Ring enhancing target-like lesions with surrounding edema are observed.

Lesions also seen in the corticomedullary junction and periventricular areas.

MRI can be diagnostic of toxoplasmosis if mass effect seen in basal ganglia or

thalamic lesions.

Infectious

Creutzfeldt-Jakob Disease

FLAIRADCFLAIR

T2

Bilateral and symmetric increased signal intensity in Basal ganglia.White arrows on the ADC image indicate the cortical ribbon sign. Symmetrical hyper intensities in the pulvinar nuclei (“hockey stick” sign) indicated by black arrows in the first two images. FLAIR imaging shows the Pulvinar sign. The criteria for which include:1. Appropriate clinical history2. Bilateral hyper intensity in the pulvinar, greater than that in the putamen;3. Appropriate imaging sequences have been performed, preferably including a FLAIR sequence in the axial plane.

Infectious

Human T- Lymphotropic Virus Type 1

FLAIR T2 T2

Thoracic spinal cord atrophy on T2 sagittal images, are observed in the later stages of the disease.

T2 hyper intense lesions were correlated with motor impairment, increased IgG in CSF, and a rapid clinical course.

Infectious

Tuberculosis

T1 Post C T1 Post C T1 Post C T1 Post C

Infarction and hydrocephalus, leptomeningeal enhancement and arachnoiditis. Both tuberculomas and pyogenic abscess are ring-enhancing with central hypo intense area, but the tuberculomas will show no restriction on ADC. MRA shows segmental areas of narrowing. In TBM, proteinaceous exudates is hyper intense on FLAIR. Spectroscopy shows a lipid peak, which can be seen in MS also due to myelin breakdown. MR Spectroscopy is also useful with tubercular abscesses showing elevated lipid/lactate without elevated amino acids.

Infectious

The most common metastases are breast cancer, lung cancer, and melanoma. The blood brain barrier restricts drug delivery from the bloodstream, making the treatment of metastatic disease difficult. Metastatic brain disease has a high mortality and morbidity rate. Patients can present with seizures, cognitive impairment, and mood disorders.

This patient had a history of breast cancer and presented 10 years later with cognitive dysfunction, depression, and neuropathy.

Metastatic Cancer

Gadolinium-enhanced MRI is the gold standard for detecting metastatic disease.

DWI correlates with histology, grade, architecture, Ki67 proliferation index, fibrosis, and prognosis. Note the lack of periventricular lesions.

T1 Post C ADCT2GREFLAIRFLAIR

Neoplasm

Adrenoleukodystrophy

Demyelination in the visual and audio pathways, pyramidal tracts, external capsule, and cerebellar white matter is observed .

Affected white matter will have prolonged T1 and T2 relaxation times. Blood brain barrier abnormalities on T1-Gd as an enhancing demyelinating edge.

Typically, sub cortical U fibers are spared as in the sagittal FLAIR image, unlike the above axial FLAIR image . There is a posterior predominance of the disease.

FLAIR T1 Post CT1 Post CFLAIR

Metabolic / Genetic

Metachromatic Leucodystrophy

T2 FLAIRT2 FLAIR

Symmetric volume loss and demyelination can be seen initially in the periventricular white matter, & then extend to the sub cortical white matter .

Atrophy, dilated ventricles, and multifocal white mater lesions in the frontal lobes have been observed.

Metabolic / Genetic

Tumefactive MS (Tumor like MS)

T2 T2

T1 Post C

T2T2

TBCNS LymphomaGBM Tumefactive MS

Tumefactive MS is characterized by a single intracranial well-circumscribed lesion > 2 centimeters in diameter with incomplete rim enhancement and often with mass effect.

The lesion can have the classic "butterfly shape" of GBM and lymphoma.

Multiple smaller lesions in the basal ganglia, corpus Callosum, spinal cord, parietal and frontal lobes suggest the true diagnosis.

MR Spectroscopy may show increased glutamate/glutamine peaks. Increased choline to N-acetyl-aspartate ratios are seen in Tumefactive MS and malignancy.

FDG-PET can be differentiating (hyper-metabolism in malignancy is > than Tumefactive MS).

Thank You !