A rare case A rare case of of NEUROMYELITIS NEUROMYELITIS OPTICA OPTICA

SPECTRUM DISORDERSPECTRUM DISORDERDr. Saran SharmaDr. Saran Sharma

MM--2 UNIT2 UNITProf SS unitProf SS unit

&Dept of neurology ICH&Dept of neurology ICH

CASE HISTORY

Manoj 1&1/2 yr old male child

first child of 3rd degree consanguineous parents

• Fever - 4 days

• Loose stools - 3 days

• Right hemiparesis - 1 day

• No history s/o any cranial nerve involvement.

• No h/o LOC/ seizures / head injury/ ear discharge.

• Past history-nil significant

• Family history-nil significant

• Developmentally normal child.

On Examination• Awake, irritable, afebrile

• No pallor/icterus/cyanosis/ clubbing/ pedal edema/ significant generalised lymphadenopathy

• No facial dysmorphism / neurocutaneous markers

VITALS :

HR – 84/min ; RR – 14/min

BP – 126/80mmHg ;

HC- 46 cm

CVS – S1S2 + , No murmurs.

RS – NVBS, no added sounds

P/A – soft, No organomegaly.

CNS examination

• Child irritable.

• Fixes and follows light.

• Pupils equal and reacting to light.

• EOM- full.

• No facial asymmetry.

• Other cranial nerves normal.

SPINOMOTOR SYSTEMRIGHT LEFT

BULK N N

TONE N

POWER UL 1/5 UL 5/5

LL 1/5 LL 5/5

REFLEXES

SUPERFICIAL

ABDOMINAL + +

PLANTAR

DEEP

BJ ++ ++

TJ ++ ++

SJ ++ ++

KJ ++ ++

AJ ++ +

SUMMARY

• Developmentally normal child

• Acute onset of right hemiparesis

• Hypertension

• Cerebrovascular accident

INITIAL INVESTIGATIONS

CBC Normal

RFT Normal

LFT Normal

ELECTROLYTES Normal

URINALYSIS Albumin NIL

Sugar NIL

Deposits NIL

ECG WNL

CXR Normal Study

CT Brain

• Left occipital region hypodensity

MRI brain

Provisional diagnosis

? Acute Demyelinating Encephalomyelits

? Atypical Posterior Reversible Encephalopathy syndrome

The child was started on:

• Inj Methylprednisolone 20mg/kg iv x 5 days

• anti hypertensive -- oral nifedipine

• H2 blockers

• meningitic dose of antibiotics

Work up for hypertension

• RFT, electrolytes- Normal

• Urine PCR- Normal, ASO titre - normal

• Renal doppler- Normal

• 24hr urinary VMA - Negative

• 8am S.Cortisol - normal

• USG & CT abdomen- Normal

• S. aldosterone and renin - normal

• During the course of treatment child developed dystonic posturing all 4limbs.

• Weakness of left lower limb in addition to right hemiparesis and head lag

•

BP

• Fundus - N

• Urgent CT brain- Diffuse parietal & occipital white matter hypodensities

Repeat CT Brain

B/L Parietal and Occipital white matter hypodensities

• DEMYELINATING DISEASE IN CHILDHOOD• ADEM

• MULTIPLE SCLEROSIS

• NMOS

• Atypical Posterior Reversible Encephalopathy syndrome

CSF analysisGlucose 57

Protein 12

Total cells 2

Gram stain Negative

Culture Negative

Latex agglutination test Negative

Electrophoresis No oligoclonal bands

CSF viral markers negative

CSF analysis

Aquaporin4 Ab in CSF Positive

Serum Ab to AQP4 Positive in 1: 10 dilution by immunofluroscent method

NMO

• Neuromyelitis optica is an inflammatory disorder -primarily affects the optic nerves and spinal cord.

• NMO IgG Ab 91% sensitive and 100% specific for clinically defined neuromyelitis optica (Lennon et al)

• No false positivity

Revised criteria for the diagnosis of NMO

DIAGNOSIS

NEUROMYELITIS OPTICA SPECTRUM DISORDER

(NMOS)

Eugene Devic, 1858-1930

French neurologist, who did the first systematic study of NMO described the sine qua non clinical characteristics, but his student Fernand Gault (1873-1936), reviewed sixteen cases and published in 1894

TYPES OF NMO

• Monophasic NMO –

ON, myelitis occurring within 1 month of each other

NMO IgG negative

• Relapsing NMO -

ON, transverse myelitis separated by months to years

accompanied by cerebral symptoms

80% positive for NMO IgG antibody

Aquaporin-4

• AQP4 is a water-channel protein (encoded by

the AQP4 gene that assembles as homotetramers in cell membranes.

• It appears to be critical in maintaining water homeostasis in settings of physiologic stress.

• Expressed in: basolateral membrane of principal CD cells in the kidney

throughout the brain particularly abundant in the optic nerves and spinal cord

Immunising event is not known

Peripheral Ig pool contains NMO-IgG

Ig have limited access to the CNS parenchyma

Astrocytic foot process (BBB)makes the extracellular

domain of aquaporin 4 channels accessible to any NMO-IgG

entering this region

Increased permeability of the BBB

Complement activation

Massive infiltration of leucocytes

Demyelination, severe neuronal injury, and necrosis hyalinisation of penetrating

vessels

NMO and Autoimmune disease

• NMO has occasionally been associated with other autoimmune diseases, including hypothyroidism, Sjogren’s syndrome (SS), systemic lupus erythematosus (SLE), pernicious anemia, ulcerative colitis, primary sclerosing cholangitis, rheumatoid arthritis, mixed connective tissue disorders, and idiopathic thrombocytopenic purpura

Treatment

Acute attacks:

• Intravenous corticosteroid therapy is commonly the mainstay of treatment.

• Patients who do not respond promptly benefited from plasmapheresis .

• Early initiation of plasmapheresis is recommended, particularly for patients with severe cervical myelitis, acute severe vision loss refractory to steroids.

To prevent Relapse:

• Maintenance immunosuppressive therapy for reducing relapses of neuromyelitis optica.

• Azathioprine (typically 2.5–3.0 mg/kg/day) in combination with oral prednisone (~1.0 mg/kg/day) reduces the frequency of attacks.

• Mycophenolate mofetil,Mitoxantrone, Rituximab and

methotrexate can induce clinical remission.

FURTHER COURSE IN HOSPITAL

• Methyl dopa added for hypertension

• In view of very young age & persistent hypertension, plasmapheresis was deferred

• Child was given ivig3.2g od x 5days

• 2nd course of Methyl prednisolone given for 5days

• trihexyphenydyl was started for dystonia

• with control of hypertension, irritability & incessant cry decreased, dystonic posturing improved

Repeat MRI Brain

TO RULE OUT AUTO IMMUNEDISEASES ASSOCIATED WITH NMO

• S.Lactate, pyruvate, ammonia- Normal

• ANA, p ANCA, c ANCA - Negative

• Antiphospholipid, anticardiolipin Ab- negative

• Thyroid profile - normal

• VEP- child not co operative

• At the time of discharge, child is conscious, oriented

• Vision normal, Cranial nerves- Normal

• Head control regained

• Power in right UL and LL 2/5, left LL 3/5

• On oral prednisolone, antihypertensives, physiotherapy.

• Plan - immuno suppressive therapy

Conclusion

• Any child presenting with transverse myelitis or optic

neuritis must be evaluated for NMO

• Seronegative NMO - kept under close surveillance

• Seropositive NMO – immunosuppressants to prevent future relapses

THANK YOU