Case report of NMO

1. An Interesting case of
quadriparesis with exophthalmos
Dr. Arka De (2nd yr PG)
Moderator: Dr. H. S. Tanwar
Assistant Professor,
Dept. Of Medicine,
Unit M1

2. • An 18 year old female patient, student by
occupation and residing in Delhi presented to
us with

3. Chief Complaints
• Protrusion of eyes- 4 months
• Headache & visual blurring- 2 months
• Weakness of all 4 limbs- 3 weeks

4. History of present illness
• Pt was apparently normal 4 months back
• Since then she complains of abnormal
protrusion of her eyeballs which was first
noticed by her mother. Protrusion was
insidious in onset, gradually progressive and
was not intermittent. It was not associated
with pain, lacrimation, fever, or facial
numbness. Redness of eyes was present.

5. • For 4 months the pt c/o head ache and visual
blurring.
• Headache was intermittent and pan cranial. It
was not throbbing in character. It was absent
when the patient woke up and tended to worsen
as the day went on. No specific triggers were
reported.
• Visual blurring was present as soon as the patient
opened her eyes with no tendency for
progression during the day.
• These were associated with nausea and vomiting
which was non projectile, non bilious and not
mixed with blood.

6. • For the last 3 weeks she c/o weakness and
clumsiness of all 4 limbs.
• Weakness was insidious in onset and gradually
progressive. Initially there was difficulty in getting
up from sitting/ squatting position, combing hair
etc. But of late the weakness has progressed and
she has difficulty in picking up a glass, wearing
slippers, walking without support etc. No
progression during the day.
• No worsening of weakness with exposure to high
temperatures
.

7. • H/O difficulty in micturition with a feeling of
incomplete evacuation present for same
duration. However, urine output was not
decreased and there was no burning micturition,
smoky or frothy urine.
• H/O episodic spasms of B/L upper limbs> lower
limbs present for the last 10 days which lasted for
less than 1 minute and were not associated with
hyperventilation, aura, premonition, confusion
etc. Similar incidents in the past were not
reported. No H/O facial or extremity twitching.

8. • There was no hist of abnormal/ decreased
sensation or pain.
• No H/O back pain or band like sensation or
pain radiating down legs/ arms
• No H/O antecedent RTI or diarrhea
• No H/O trauma, dog bite or recent vaccination

9. • H/O palpitations (intermittent but frequent),
increased appetite and heat intolerance with
increased sweating was also present for the past
year.
• H/O recurrent oral ulcerations mainly over the
palate which were predominantly painless. No
H/O nasal or genital ulceration.
• No H/O arthralgias, mylagia, rash,
photosensitivity, pruritus, fever etc.
• No H/O vertigo, alteration of sensorium/
abnormal behaviour, ear discharge etc.
• No H/O abd pain, jaundice, diarrhea, constipation
etc

10. • No H/O neck pain.
• No H/O cough, chest pain, diff in breathing etc
• No H/O bleeding from any site.
• No H/O drug abuse.
• No hist s/o euphoria, depression, memory
loss.
• No H/O sleep disturbance
• No H/O wt loss

11. Past History
• No H/O Kochs, contact with a pt. of Kochs,
surgical intervention, blood transfusion etc.
• Not known diabetic or hypertensive.

12. Personal History
• Resident of Delhi
• Student
• Mixed North Indian diet
• Non smoker
• Non alcoholic
• No h/o sexual promiscuity, tattooing, iv drug
abuse or other high risk behaviour.

13. Menstrual History
• Age at menarche- 13 years
• H/O amenorrhea present for past 2 months

14. D/D BASED ON HISTORY

15. Condition Points in Favour Points against
Graves disease with
thyroid myopathy
Protrusion of eyes,
increased apetite,
palpitations, heat
intolerance, proximal
weakness etc
Hesitancy in micturition,
tonic spasms, oral
ulcerations
SLE with neuropsychiatric
manifestations
Female sex, oral
ulcerations, weaknes,
spasms
Protrusion of eyes
Chronic meningitis (TBM) Headache, visual blurring,
weakness, long history
Protrusion of eyes,
absence of fever and wt
loss
Space occupying lesion
(intracranial/ brainstem)
Headache, visual blurring,
weakness
Hesitancy in micturition,
oral ulcers

16. Examination
• Alert, conscious and oriented to time, place
and person
• No pallor, cyanosis, clubbing, icterus, oedema,
lymphadenopathy.
• JVP- not raised
• Pulse- 120/min
• BP- 130/70 mm of Hg
• RR- 16/min

17. • B/L exophthalmos- both upper and lower
sclera visible; Naffziger’s sign positive.
• Stellwags, Dalrymple and Von Graefe signs
positive with negative Joffroys and Moebius.
• Thyroid enlarged, 6 cm, both lobes
symmetrical, firm in consistency, smooth, no
nodularity, mobile, warm to touch, non tender
with no thrill. Possible to get below the
swelling. No bruit audible.
• Diameter of neck-

18. • Respiratory system – B/L NVBS, no wheeze/
creps/ rub
• CVS- S1, S2 audible and normal, no S3/ S4/
murmur/ rub/ scratch
• P/A- soft, non tender, no organomegaly, no
free fluid, BS+

19. CNS
• GCS- E4V5M6
• No meningeal signs
• L lateral rectus palsy +
• Upbeat nystagmus
• Other CN- WNL
• Fundus- B/E WNL
• All sensations intact
• Tone- increased in all limbs (clasp knife)

20. • Power
• Abdominal reflex- Absent
• All DTRs exaggerated
• B/L plantar extensor
Right Left
Upper limb 4-/5 2/5
Lower limb 3/5 3/5

21. Provisional Diagnosis
• Graves disease + SLE with neuropsychiatric
manifestations (myelopathy)

22. D/D

23. Condition Points in Favour Points against
Graves + SLE with
neuropsychiatric
manifestations (? Myelopathy)
Features of thyrotoxicosis,
ophthalmopathy + female sex,
oral ulcers, quadriparesis with
UMN signs
Graves + MS (clinically isolated
syndrome)
Female sex, age, quadriparesis
with UMN signs, bladder
involvement, spasms
Oral ulcers
Space occupying lesion
(brainstem)- glioma,
medulloblastoma etc
Quadriparesis with UMN signs,
lateral rectus palsy, vertical
nystagmus
Exophthalmos, oral ulcers
Cavernous sinus thrombosis
with cortical venous extension
Headache + lat rectus palsy
f/b UMN type weakness;
Exophthalmos
Quadriparesis, absence of 3, 4,
5 CN involvement, oral ulcers

24. INVESTIGATIONS

25. Haemogram
ESR 14
Hb% 14
TLC 5100
DLC 67/30/3
Platelets 2.3 Lakh
Reticulocyte Count 1.1
PCV 42.3
MCV 91

26. Peripheral Smear
• RBC- normocytic, normochromic
• WBC- lower side of normal
• Platelets- adequate

27. Biochemistry
RBS 105
Urea/creat/uric acid 20/ 0.9/ 2.3
Bilirubn (tot/ dir/ ind) 1.4/ 0.4/ 1.0
SGOT/SGPT/ Alk phos 22/ 40/ 92
Protein ( Tot/ alb/ glob) 7.0/ 4.4/ 2.6
Na/ K 147/ 4.3
Ca/ Phos 9.1/ 4.0
Amylase 53

28. • Ionised Calcium- 1.25
• PTH intact- 42.9
• ABG- WNL
• HIV 1&2- NR
• HBsAg- NR
• Anti HCV- negative
• Urine R/M- WNL

29. ECG Sinus tachycardia
CXR WNL
USG abdomen WNL
2d Echo WNL

30. Thyroid Profile
Hormone Value Reference range
TSH 0.003 µIU/L ( 0.5 – 5 µIU/L
fT3 2.6 ng/dL (0.6 2.2 ng/dL)
fT4 4.88 pg/mL (2 – 4.4 pg/mL)
Anti- TPO- 0.13 negative

31. USG NECK
• R thyroid lobe 1.9 cm AP
• L thyroid lobe 1.8 cm AP
• Both lobes show altered echotexture
• Vascularity normal
• Multiple cystic changes with comet tail
artefacts
• Subcentimetric LN left side

32. RAIU
• At 2 hours- 8.3
• At 24 hours- 45.6 (Normal 5-25)
………………..Impression: Grave’s disease

33. Value Reference range
Ig A 188.3 mg/dl 90-30 mg/dl
Ig G 958.6 mg/dl 710-1520 mg/dl
Ig M 103.5 mg/dl 40-250 mg/dl
C3 103.6 mg/dl 80-160 mg/dl
C4 18.0 mg/dl 20-40 mg/dl

34. ANA by ind IF on HEP 2 cells
…..1+, speckled, no mitosis
ds DNA by elisa
…….borderline positive

35. CEMRI brain, orbit and spine
• Ill defined area involving the dorsal aspect of brainstem
(predominantly pons and midbrain), hypointense on
T1W and hyperintense on T2W and FLAIR.
• Long T2 hyperintensity involving caudal aspect of
medulla and upper spinal cord from C1-C3 vertebrae
extending along the entire cross section of spinal cord
with associated mild cord enlargement.
• Impression- primary demyelinating disease likely
Neuromyelitis Optica

38. CSF
• Cytology- 10 cells, all lymphocytes
• Biochemistry- sugar- 65 mg %
protein- 80 mg %
• Gm stain, C/S, ZN stain, India Ink- negative
• ADA, TB-PCR- negative
• Oligoclonal bands- Negative

39. VEP
• Normal P100 latency and amplitude in both
eyes
• However, P100 latency in Right eye is 8.6ms
more than P100 latency in Left eye.

41. NMO-Ig G or Anti AQP4
POSITIVE

42. Final Diagnosis
• Grave’s disease with NMO spectrum disorder
with (?) SLE

43. DISCUSSION

44. NMO….current concept
• It is NOT a variant of MS
• The distinction between NMO and MS is very
important as the treatment and prognosis of
the 2 disorders differ significantly.
• NMO is not single disorder (Devic’s disease)
but rather a spectrum of disorders unified by
the finding of anti- aquaporin 4 antibodies.
Jacob A mcleon, Nakashima I et al. J Neurol
Neurosurg Psychiatry 2013;84: 922-930

45. Differences between NMO
&
Multiple Sclerosis

46. Epidemiologic
• Although female preponderance is seen in
both diseases, it is much higher in NMO with
some studies reporting a 10:1 female
preponderance
Wingerchuk DM. Neuromyelitis optica: effect of
gender. J Neurol Sci 2009;286:18-23.

47. Clinical Features
• Classical NMO- optic neuritis and acute
transverse myelitis. Occasionally, these events
will occur simultaneously but usually they evolve
months to years apart.
• “NMO spectrum disorders” includes other
syndromes involving the cerebrum and
neuroendocrine systems in patients who are
seropositive for NMO-Ig G and who may or may
not also have experienced optic neuritis and
myelitis

48. NMO spectrum disorders
Wingerchuk DM, Lennon VA, Lucchinetti CF, et al. The spectrum of
neuromyelitis optica. Lancet Neurol 2007; 6: 805-815

49. • NMOSD include limited forms of NMO
(recurrent ON or TM), brainstem disorders
(including intractable hiccup and nausea/
vomiting)and hypothalamic disorders
(including SIADH)
• Optic neuritis can occur in both MS and NMO,
may be unilateral or bilateral, simultaneous or
sequential BUT is uaually more severe in
NMO as confirmed by ocular coherence
tomography.

50. • NMO attacks are usually severe and often only
partly recover; secondary progressive disease is
very uncommon. Disability is largely due to the
cumulative effect of clinical attacks.
• MS attacks are mild to moderate in severity,
usually recover well early in the disease and
secondary progressive disease is the cause of
late-course disability.
Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A
secondary progressive clinical course is
uncommon in neuromyelitis optica. Neurology
2007; 68: 603-605.

51. NeuroimagingMRI SPINE
shows T2
hyperintensity
MS
peripheral
<1 vertebral
segment
NMO
Central
>3 contiguous
vertebral
segments
Detection of a LETM lesion on MRI is the most specific
indicator of NMO and should be done during acute
myelitis attack

52. MRI BRAIN
• 60% of NMO patients have nonspecific white
matter lesions and 10% have lesions that
meet radiological criteria for MS
• Therefore brain MRI lesions do not exclude
diagnosis of NMO.
Pittock SJ, Lennon VA, Krecke K, et al. Brain
abnormalities in neuromyelitis optica. Arch
Neurol 2006; 63: 390-396.

53. • May have cloud like enhancement in NMO
• Corpus callosum lesions in typical MS are
oriented perpendicular to the ventricular surface
while in NMO such lesions are often linear and
follow the axis of the corpus callosum itself.
• Relatively NMO specific areas are midline Aqp4
rich regions- hypothalamus and periaqueductal
brainstem.
• Unlike MS, MR spectroscopy shows normal N
acetyl aspartate: creatinine and choline:
creatinine in NMO

54. CSF
Parameter NMO MS
Cytology Vary; can be high (50-
1000); often neutrophil
predominant
Mild lymphocytic
pleocytosis (<25)
Protein Often high (100-500) Variable
Oligoclonal Bands <20-30% Approx 85%

55. Anti AQP4
• Anti aquaporin 4 antibody ( previously called NMO Ig
G) has a 85-100% specificity and 47-91% sensitivity for
NMO depending on the method used.
• Serum testing is generally more sensitive than CSF
testing.
• CSF GFAP might serve as a diagnostic marker of NMO
in NMO-IgG seronegative patients.
Takano R, Misu T, Takahashi T, et al. Astrocytic damage is
far more severe than demyelination in NMO: a clinical
CSF biomarker study. Neurology 2010;75:208–16.

56. Association between NMO, MS and
other autoimmune disorders
• Higher frequency of clinical and serological
autoimmune accompaniments in NMOSD than in MS.
• Antinuclear antibodies (dsDNA, extractable nuclear
antigen) are the most common non-organ-specific
autoantibody accompaniments and autoantibody
markers of Sjogren’s syndrome or SLE are found in 47%
of patients with NMOSD. Thyroid disease may occur in
upto one third.
Pittock SJ, Lennon VA, de Seze J, et al. Neuromyelitis
optica and non organ-specific
autoimmunity. Arch Neurol 2008;65:78–83

57. Treatment Differences
• MS treated with immunomodulators while NMO
typically treated with immunosuppressants.
• Several conventional MS drugs seem to worsen
NMO
• Interferon-β is contraindicated in NMO because
of its inefficacy and tendency to cause severe
relapses.
• Natalizumab and Fingolimod have also been
reported to fulminantly exacerbate NMO

58. REVISED DIAGNOSTIC CRITERIA
OF NMO

59. Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised
diagnosticcriteria for neuromyelitis opti ca. Neurology 2006; 66:
1485-1489.

60. TREATMENT OF NMO
Ref:
Jacob A mcleon, Nakashima I et al. J Neurol Neurosurg
Psychiatry 2013;84: 922-930
and
CME Neuromyelitis optica spectrum disorders: diagnosis and
treatment; Dean M Wingerchuck, Mayo Clinic

61. Acute Exacerbation
• Early corticosteroid treatment, typically 1g of
intravenous methylprednisolone for 5 days
followed by oral prednisone (1 mg per kg body
weight) for a month and then a gradual tapering
off over a 6–12 month period.
• Relapses that do not respond to intravenous
steroids could benefit from plasma exchanges;
typically 5–7 exchanges over a 2-week period.
• The threshold to initiate PLEX should be low.

62. Prevention of Relapses

63. Symptom management &
Rehabilitation
• Pain, stiffness, fatigue, bladder and bowel
symptoms, have to be managed with
appropriate medications.
• Carbamazepine around 100–400 mg/day in
divided doses, often leads to rapid and
gratifying relief of tonic spasms.
• Rehabilitation is important.
• Ideally a multidisciplinary approach should be
taken.

64. WHY SLE?

65. ACR classification criteria
• At least 4 of the following criteria-
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Renal disorder
8. Neurologic disorder
9. Hematologic disorder
10. Anti ds-DNA or anti SM or antiphospholipid
11. ANA
? ?

66. ??

67. ACR classification of neuropsychiatric
syndromes in SLE
Central Nervous System Peripheral Nervous System
Aseptic meningitis GB syndrome
Cerebrovascular Disease Autonomic disorder
Demyelinating Syndrome Mononeuropathy, single/ multiplex
Headache Myasthenia
Movement disorder Cranial Neuropathy
Myelopathy Plexopathy
Seizure Polyneuropathy
Acute confusional state
Anxiety disorder
Cognitive dysfunction
Mood disorder
Psychosis

68. • SLE myelopathy should be distinguished from
NMO in the setting of anti aquaporin 4 positivity
“Current Diagnosis and Treatment- Rheumatology”
• Patients who meet formal diagnostic criteria for
connective tissue diseases such as SLE or Sjogren
syndrome and possible NMO should be tested
for NMO-Ig G. Those who are seropositive for
NMO-Ig G most likely have coexisting
autoimmune diseases rather than “lupus
myelitis”…..
CME Neuromyelitis optica spectrum disorders:
diagnosis and treatment; Dean M Wingerchuck,
Mayo Clinic

69. Thank You…..