2. INVESTIGATIONS
 Mayo clinic extensive work –up negative
 Serology, CT Body, Mammogram, testicular U/s
 Pet Congectival, Lung parenchymal biopsies.
 ACE,ANA ssB minimally elevated one patient each
 Para neoplatic screen negative in all 5 of 6 mayo Pets
tested (4 serum: 2CSF)
 NMO-lgG Negative in 4 all checked

3. PATHOLOGY
 4 Patient biopsied (3 Mayo: Belgium):3 cerebellum 1 Pons
 Marked lymphocytic infiltrate (Predominantly CD3 reactive T
lymphocytes, Some CD20 positive B lymphocytes. CD68
positive histiocytes and activated microglia present)
 White matter with peri vascular predominance and more diffuse
parenchyma inflammatory infiltrate
 Myelin intact, special stains for fungi, Mychobecteria negative
 No characteristic finding of
sarcoidosis, histiocytosis, lymphoma, lymphomatoid, granulom
atosis
 Multiple sclerosis or other disease

4. TREATMENT AND OUT COME
 7 Patient 1g Iv methylprednisolone
 all improved initially.
 PO prednisone in 1 without marked early
improvement.
 Varied long-term outcome- ranged from
excellent to incomplete with substantial deficits
remaining Myelopathy in Belgium case.

5. CONCLUSION
 Definable, treatable, inflammatory, CNS brainstem-
predominant syndrome
 Similar clinical, Radiological, Pathological
Syndrome responsive to Immunosuppression
especially steroids
 No other diseases found despite extensive and
prolonged follow –up
 Difficulty biopsy: rule out other
competing, diseases, consider biopsy
 Therapy with high dose corticosteroids.
 Prolonged therapy commonly
needed, immunosuppression with steroid- sparing

6. EMERGING THERAPIES IN MS
 Natalizumab: Monitoring advances serum
JCV antibody test projecting PML risk
 Combination Therapy: Await combi Rx
interferon B -1a IM/glatiramer acetate
 Fingolimod: first approved oral MS
Medication: long term safety

7. EMERGING THERAPIES IN MS - ORAL MEDICATION
 Cladribine: approved in Russia and Australia
disappoint reviews at FDA Europe: helted
development
 Laquinimode: mixed results: BRVO missed
reducing relapse (Primary end point)
 BG00012: Promising results MRI and relapse
 Teruflunimide: early promising results MRI and
relapse

8. DIFFERENTIAL DIAGNOSIS OF ACUTE TRANSVERSE MYELITIS
Demyelinating Disorders Parasitic Systemic sclerosis
Multiple sclerosis Neurocysticercosis Neurocysticercosis
Neuromyelitis optica Schistosoma Behçet syndrome
Acute disseminated Gnathostoma Vascular Disorder
Encephalomyelitis
Angiostrongylus Anterior and posterior
spinal artery infarction
Idiopathic Toxocara Arteriovenous fistula

9. Postvaccinial Viral (human T-cell Hematomyelia
lymphotropic virus and (arteriovenous
Rabies HIV cause more chronic malformation,
myelopathies) cavernoma,
Diphtheria-tetanus-polio bleeding diathesis,
Herpesvirus: herpes Osler-Weber-Rendu
Smallpox simplex virus, syndrome)
Measles varicella-zoster virus
cytomegalovirus,
Rubella human herpes virus Fibrocartilaginous disk
types 6 and 7 embolism
Japanese B encephalitis Epstein-Barr virus
Neoplastic
Epstein-Barr virus Flaviviruses: Dengue Primary intramedullary
feverJapanese B B tumors (lymphoma,
Pertussis encephalitis, st Louis ependymoma,
encephalitis tickborn actrocytoma, and
Influenza encephalitis, West hemangionlastoma
Nile virus or metastatic
Hepatitis B intramedullary tumors

10. Infection Orthomyxovirus: Paraneoplastic (may
Bacterial Influenza A virus also cause chronic
Spinal cord abscess myelopathy)
(epidural or Paramyxovirus:
intraparenchymal) Measles virus Lung and breast
due to spread from Mums virus carcinomas most
systemic infection common
Picornaviruses:
Myco plasma Coxackievirus types A Amphiphysin and
Borrelia burgdorferi AndB, echoviruses Collapsein
Enteroviruses 70 and 71 Response- mediator
Treponema pallidum hepatitis A and C protein 5-lgG most
common autoantibody
Myconacterium Poliovirus types I,2 associations
Tuberculosis And 3
Actinomyces Other inflammatory
Disorders
Fungal Systemic lupus
Blastomyces Erythematosus
Coccidiodes Siogren syndrome
Cryptococcus Mixed connective tissue
Aspergillus disorder

11. DIFFERENTIAL DIAGNOSIS OF CRONIC MYELOPATHIES
Idiopathic Inflammatory Spinocerebellar ataxias
Demyelinating Diseases
ALS
Primary progressive Vascular
multiple sclerosis Cerebral autosomal
Autoimmune dominant
Paraneoplastic myelopathy
arteriopathy Anteriopathy with
Other autoimmune subcortical infarcts and
Myelopathy Leukoencephalopathy
Autoimmune/paraneoplastic
motor neuron disorders Dural arteriovenous
malformatiorv’fistula

12. Infectious Compression/Structural
HIV myelopathy Tumor Spondylosis
Human T-cell lymphotropic Tumor
Syrinx Syrix
virus—associated
myelopathy/ Inflammatory
tropical spastic paraparesis Sarcoidosis
Borrellosis Vasculitis
Schistosomiasis Bebcet syndrome
Borrelia burgdorferi Sjogren syndrome
Hereditary/Degenerative Deficiency status
Vitamin- B12
Hereditary spastic Copper
paraparesis
Friedreich ataxia
Adrenomyeloneuropathy

13. COMPARIS0NON OF MS, NEUROMYELITIS, OPTIC, ACUTE DISSEMINATED ENCEPHALOMYELITIS, AND
PARANEOPLASTIC MYELOPATHIES AND ACUTEIMMUNE/OARANEO PLASTIC MOTOR NEURON DISEASE
Characteristic Multiple Neuromyelitis Acute Paraneoplastic Auto immune/
Sclerosis Optica disseminated Myelopathy Paraneoplastic
Motor neuron
Disease
Antecedent Variable Variable Typical No No
infection or
Immunization
Median age 29 29 Children to 62 Vriable
of onset
(years)
sex( F:M) 2;1 3-9:1 Similar Similar Slight female
Predominate
Frequency Common Intermediate Intermediate Rare Extremely
rare
Epidemiology White Disproportion Any Unknown Unknown
ately

14. Characteristic Multiple Neuromyelitis Acute Paraneoplastic Auto immune/
Sclerosis Optica disseminated Myelopathy Paraneoplastic
Motor neuron
Disease
Neural None Neuromyelitis None Collapsin Variable
autoantibody optica lgG response-
associations mediator
protein5 and
amphiphysin
lgGs most
common
Brain MRI Periventricular Hypothalamic, Subcortical, Normal Normal
white matter periventricular, may involve
lesions particularly deep gray
thirdffourth matter
ventricle;
cloudlike
enhancement

15. Characteristic Multiple Neuromyelitis Acute Paraneoplastic Auto immune/
Sclerosis Optica disseminated Myelopathy Paraneoplastic
Encephalomyel Motor neuron
iti Disease
Chronic Interferon Azathioprine None Cancer Cancer
treatment Beta steroids, treatment. treatment.
glatiramer mycophenolate steroids, IVIg. steroids, IVIg,
acetate, mofetil, plasmapheresis cyclophospham
natalizumab in rituximab ,cyclophospha ide,
severe cases mide,azathiopri azathioprine,
ne,mycophenol mycophenolate
ate mofetil mofetil
Prognosis Majority Moderate to Good; Poor; most Poor response
ambulatory severe monophasic Wheelchair to
after 20 years disability dependent treatment; may
over time; within 2 to 5 have slower
most patients years oroaression
disabled than ALS