P.A.R is a 36-year-old female who presented with a 2-year history of fluctuating proximal muscle weakness affecting her lower and upper limbs, neck, eyes, and swallowing muscles. On examination, she had ptosis of the left eye, limited eye abduction with horizontal diplopia, a positive curtain sign, reduced muscle power in her upper and lower limbs, and fading speech. Testing revealed elevated acetylcholine receptor antibodies, supporting a diagnosis of generalized myasthenia gravis.

1. GRAND ROUND PRESENTATION
ALEX ELIFURAHA MSOKA MD5
MUHIMBILI UNIVERSITY
TANZANIA
2016

2. • Name : P. A.R
• Age : 1975
• Sex : Female
• Address: Ilala Bungoni
• Referred : Amana
• Informant: Patient and her husband
• Seen at neurology clinic

3. Main complaints
• Lower limb weakness -2 years
• Difficult in swallowing - 1 year

4. HPI
Lower limb weakness 2 years
-started to be noticed when she was eight months of
pregnancy
- experiencing frequent falls after walking a some distance
appx 150m, commonly when she was walking home from
ANC/church
-She would fall down on her knees, and she would woke on
herself after a few minutes of rest by supporting herself on
her knees.
- she estimate this to have occurred 5 times before delivery

5. • Prior to the falls she denied any hx of;
- Awareness of heart beats
-Shortness of breath
-chest pain
-headache or dizziness
-excessive yawning
-sweating
• During the falls, there was no history of:
– loss of consciousness
– convulsions

6. • Despite the fact that these falls were recurring for a period
almost of two months, she did not seek any medical
attention as she was attributing it to her pregnancy.
• After delivery she did not experience any further falls.

7. • But three months later she developed inability to lift her
neck from a bent position,
• And this was noted while sweeping the compound
• It was overcomed by forcefully lifting her trunk.
• It was not associated with pain in the neck nor was it
preceded by trauma

8. • A month after development of neck weakness,
the same time she developed inability to lift
her arms above the shoulders,
-unable to lift her baby
- unable to comb her hairs

9. • However these symptoms were fluctuating with variable
disease free periods ranging from 2days to 3wks
• Prominent upon physical activity and were relieved by rest
• More frequently noted more during the end of the day

10. • These symptoms kept on remitting and relapsing for almost
the whole year
• She attended several times at Amana hospital where she was
told to have a neurological problem and was kept on daily
neurotone tablets.

11. • A year later the lower limb weakness recurred
• And this time it was more severe and progressive
-initially was characterized by frequent falls in which this time
she couldn't walk up by herself
- later on she was unable to walk without support

12. • During this time she started to experience difficult in swallowing
• She describes it as not having enough strength to accomplish the act of
swallowing
• non progressive and was experienced when taking both solid and liquid
foods
• was not associated with painful swallowing but she reported h/o
-getting tired of chewing and could not
- open her mouth wide open
• This was also noted more towards the end of the day in such a way that
some days she was unable to take dinner.

13. • At the same time she noticed that her left eye was closing
spontaneously during the day even when she was not feeling
asleep.
• But She couldn't open it until after about (say 5-10 min)
• However this was not associated with
– lack of sweat in one side of the body
– chest pain
– haemoptysis
– trauma

14. • She also noted that her speech was fading away
some of the times,
• she could not shout or maintain her voice in the
same tone while singing and later on even while
talking

15. • The condition kept on remitting and relapsing
and she continued to attending Amana for
another 8 other months before she was
referred to MNH Dec 2010
• Admitted for one day, and discharged to do
invs as outpatient
• Was not put on any medication

16. Througtout the course of this illness
– No history bone pain
– No history of numbness
– No history of fecal nor urine incontinence
– No Hx of fever
– No Hx of joint pain
– No history of skin changes.
– Irritability
– No difficulties in sleep/nor excessive sleep

17. • ROS
GUS
No abnormal vaginal discharge
Normal micturation habit

18. PAST MEDICAL HISTORY
• Only one admission at MNH for one day
• No Hx of surgery
• not known to have DM,HT
• No known drug allergy

19. FAMILY AND SOCIAL HISTORY
• Married with three children
• Standard seven leaver
• Husband is working as a cook, working missionary residency .
• She was a petty trader before the illness
supplying groundnuts to different supermarkets
(3 sacks per months profit 200,000? Currently <1 sack)
• No smoking/alcohol
• The is no family hx of similar diseases in the family
• No family history of DM in family

20. GYNACOLOGICAL HISTORY
Menstrual Hx
• Cycle regular (28-30)
• Periods 3-4 days
• 2-3 pads per day

21. DIETARY HISTORY
• Takes normally the available food;
– tea/bread
– Ugali/banana/rice
– Vegetables/beans/fish/
Conclusion: Adequate diet in quality
?Quantity - sometimes unable to eat due to the
difficult in swallowing.

22. Summary
P.A.R , 36yrs,female married, mother of
three children, who presented with 2 years
history of fluctuating proximal muscle
weakness and fatigue, more marked towards
the end of the day, affecting the lower, upper
limbs the neck with ocular and the bulbar
symptoms

23. Examination
20th May 2011
General Examination
• Fully conscious,
• Oriented to TPP
• BMI- 22 .5
• Normal hair texture & distribution
• Not jaundiced
• Mild pallor
• No oral lesions,
• Afebrile - 37.4 o C
• Not dyspnoeic
• Not cyanosed
• No finger clubbing
• No skin lesions
• Normal nails
• No lymphadenopathy
• Warm extremities
• No LL edema

24. Examination of the eyes
Lt
• Partial ptosis with
intepalpebral aperture of 6mm
• Va 6/6 with N visual field
• Limited abduction with
horizontal Diplopia
• No stabismus or nystagmus
• Conj, cornea , ant chambers N
• Pupils
• Fundus N
Rt
Interpalpebral diameter 9mm
VA 6/6 with N visual field
Normal range of mvt in all
directions
No strabismus or nystagmus
• Conj, cornea , ant chambers N
• Fundus N

25. CNS
Higher centers:
• Conscious
• Oriented to TPP
• fading speech when counting from one to 20
• Intact long/short term memory

26. CNS
Cranial Nerves:
– I = normal smell
– II, III, IV ,VI ( as per eye e)
– V Could clench teeth
– VII = No facial asymmetry
– VIII = can hear
– IX, X = Normal gag reflex
– XI = Can turn head against resistance
– XII = No tongue deviation

27. CNS
Upper Limbs
• Motor System
– Normal musle bulkiness
– No involuntary movements
– Tone: Reduced
– Power:
• Shoulder abductor, adductor, flexor, extensor G2
• Both elbow flexor, extensor G3
• Both wrist flexor, extensor G3
• Both hand flexor of MCP joints G 3
– Co ordination: could N

28. CNS
Lower Limbs
• Motor System
– Normal bulkiness
– No involuntary mvts
– Gait – couldn't be assessed
– Tone: Reduced
– Power:
• Hip abductor, adductor, flexor, extensor G2
• Both knee flexor, extensor G3
• Both ankle flexor, extensor G3
– Co ordination: N

29. CNS
• Reflexes
– Knee: N
Ankle: N
– Babinski : Plantar flexion
– no sustained clonus
– Abdominal: Present

30. CNS
• Sensory:
– Normal Vibration
– Normal Joint position sense
– Normal light touch, pin prick sensation
• Spine: normal

31. R/S
• RR = 16 breaths/min
• No surgical nor therapeutics marks
• Symmetrically chest expansion
• Central trachea
• No area of tenderness, nor palpable mass
• Normal TVF, resonant percussion note
• Normal vocal resonance
• Vesicular breath sounds, no crepitations

32. CVS
• PR 88 beats/min (regular, good volume, normal
character, synchronous with other peripheral pulses)
• BP 110/70
• JVP – not raised
• No precordial hyperactity
• AB5th ICS MCL
• S1 & S2 heard, normal
• No pericardial rub
• No carotid bruit
• No hepatic bruit

33. P/A
• Normal contour
• No surgical scars/therapeutic marks
• Moves with respiration
• No visible peristalsis, no distended veins
• L°, S°, K°
• Tympanic percussion note
• No shifting dullness/fluid thrill
• Normal bowel sounds.
• DRE - Normal findings

34. SUMMARY
P.A.R , 36yrs,female married, mother of three
children, who presented with 2 years history of
fluctuating proximal muscle weakness and
fatigue, more marked towards the end of the day,
affecting the lower, upper limbs the neck with
ocular and the bulbar symptoms
O/E
she has a fading speech, limited abduction on lt
eye with horizontal Diplopia, a positive curtain
sign, reduced muscle power upper and ll P>D,
with no fasciculation.

35. Video clips
• Fading speech
• ptosis
• Curtain sign
• lifting of the hands

36. PROVISION DIAGNOSIS
1. Myasthenia gravis- generalized form
ddx
Lumberton Eaton syndrome
Oculopaharyngeal muscular dystrophy
Motor neurone disease

37. • Myasthenia gravis
-fluctuating muscle weakness and muscle fatigue
- worse towards the end of the day
-female ( 6:4)
-age of onset(2nd 3rd decade) Female incidence peaks in the third dec
- ocular involvement ( ptosis and Diplopia)
- bulbar muscle
- proximal weakness
-Remittent and relapsing pattern
• Negative
-rarely starts with weakness of the lower limb muscle

38. • Lambert-Eaton myasthenic syndrome
-fluctuating muscle weakness that typically starts with
the lower limbs
-5% may present with occular and bulbar symptoms
• Ve
-Worse in the morning, improve with exercise
-Autonomic symptoms is a feature e.g dry mouth
-Symptoms of underlying malignancy absent( SmCC)

39. • Oculopaharyngeal muscular dystrophy
proximal muscle weakness
with unilateral ptosis
bulbar symptoms
-ve
Fluctuating muscle weakness
No evidence of muscle atrophy
rarely starts with weakness of the lower limb muscle

40. • Motor neurone disease (amyotrophic lateral
sclerosis)
- widespread nature of the symptoms(upper & LL limbs,
bulbar symptoms)
Ve
fluctuation in symptoms
No signs of mixed upper and lower motor neurone lesion

41. INVESTIGATIONS
May 2011
WBC 6.78 4.0-11.0 K/UL
NEU 3.97 2.0-6.9
LYM 1.48 0.6-3.4
MONO 0.51 0.0-0.9
EOS 0.52 0.0-0.7
BASO 0.126 0.0-0.2

42. INVESTIGATIONS
May 2011 Normal range
RBC 4.29 4.04-6.13 M/L
HGB 10.2 12.6-18.1 g/dl
HCT 37.8 37.7-53.7%
MCV 69.2 80.0-97.0 fl
MCH 21.9 27-31.2 pg
MCHC 31.6 31.8-35.4
RDW 16.9 11.6-14.8 %
PLT 374 142-424 K/L
ESR 12mm/hr

43. INVESTIGATIONS
May 2011
ALB/GLOB 1.1 1-999999
AlbG 36 35-50
Alkp 117 40-150u/l
ALT 10 0-55u/l
AST 23 5-34u/l
GGT 35 9-36
BilD 4.6 0.0-8.6umol
BilT 6.7 3.4-20.5umol
Ca 2.20 2.22-2.70mmol
Crea 69.4 62-115umol
Urea 3.2 3.2-7.4mmol/l
K 3.6 3.5-5.5 mmol/l
Na 138 136-145 mmol/l
Phos 0.81 0.7-1.5 mmol/l

44. INVESTIGATIONS
May 2011
LDH 200 125-243U/l
TP 70 60-80 g/l
RBG 2.92 2.9-7.1 mmol/l
CHOL 6.8 0.00-5.18
mmol/l
Trig 0.88 0.0-1.69mmol/l

45. nerve conduction studies
Motor function in antidromic pattern
nerve Nerve conduction velocity
Right Peroneal nerve
54.1m/s
Right Tibial nerve
52.5m/s
Left Peroneal nerve
52.5m/s
Left tibial nerve 54.1m/s

46. Creatinine kinase
• Creatinine kinase – 22 U/L (20-200)

47. Acetocholine receptor antibodies
highly elevated 470nmol/l ( absent not more than
0.05nmol/l)
Specificity nearly 100%
we wished we would have done EMG studies –no
needles

48. 15% have MG have thymoma or thymus hyperplasia
-normal lung fields
-cardiac shadow normal size
- no evidence meditational
widening
- free cardiothoracic and
and cardiophrenic angles

49. MRI

50. Screening for other autoimmune diseases
• FBG 4 mol/l(normal)
• rheumatoid factor- negative
• Antinuclear antibodies (pending)

51. Thyroid function test
Parameter Patients Reference
T3 (nmol/L) 1.73Pg/ml 1.45-3.48
T4 (nmol/L) 0.98ng/dl 0.71-1.85
TSH (uIU/mL) 0.846 uIU 0.49 – 4.67

52. • HIV serology-negative
• Serum ferritin – Low
• Stool for occult blood negative

53. Discussion
Myasthenia Gravis
Why? relatively rare disease

54. What is it?
• Is an antibody-mediated neuromuscular disorder characterized by
weakness and fatigability of skeletal muscles.
• It occurs in two forms:
-ocular myasthenia ( eyelids and extra ocular muscles)
- generalized disease (ocular+ bulbar, limb, and respiratory muscles).
• It has a bimodal distribution
– second and third decades (female predominance)
– and a late peak in the sixth to eighth decade (male predominance).
• No ethical preponderance Caucasians =black Africans, prev in US 2 in
1,000,000 population

55. pathophysiology
Auto antibodies to the AR at the NMJ
Block neuromuscular transmission
Initiate complement-mediated
inflammatory response
Reduce number of AR
Damages end plate

56. • Approximately 10–15 percent of patients with MG antibodies not
directed towards AR
• Seronegative MG .
• Seronegatives MG have auto antibodies towards a muscle-
specific kinase (MuSK)
• which is an ACHR complex-associated protein responsible for
postsynaptic differentiation and clustering of acetyl choline
receptors
• Reduce no of functioning Acetocholine receptors

57. Thymus in pathogenesis of MG
• In MG ~65% has the thymus hyperplasia and 10% thymoma
• In the thymus there are Muscle-like cells which are called
myoid cells
• They bears AChRs on their surface, may serve as a source of
auto antigen and trigger the autoimmune reaction within the
thymus gland.
• These auto antibodies can circulate and act on other
Acetocholine receptors in the body

58. Clinical presentation
• The cardinal feature of myasthenia gravis is fluctuating skeletal muscle
weakness, often with true muscle fatigue.
• The weakness may fluctuate throughout the day, but it is most commonly
worse later in the day or evening, or after exercise
• > 50 percent of patients present with ocular symptoms of ptosis and/or
Diplopia.
• Of those who present with ocular manifestations, about half will develop
generalized disease within two years .

59. • About 15 percent of patients present with bulbar symptoms.
- These include dysarthria, dysphagia, and fatigable chewing.
• Less than 5 percent present with proximal limb weakness
alone.
• Less common presentations include isolated neck weakness,
isolated respiratory muscle weakness, and distal limb
weakness.

60. Precipitants
• Pregnancy
• Anaemia
• infections
• Drugs
-Antibiotics - Aminoglycosides:
-Quinolones
- Macrolides

61. • Nondepolarizing muscle relaxants for surgery
• Beta-blocking agents
• Quinine derivatives
• Statins

62. How do you make a diagnosis
• History and physical findings-
• Tensilon test
• Serological test
-ACHR
-MUSK
• Electro diagnostic studies
-Single-fiber electromyography
-Repetitive nerve stimulation

63. RX
• Symptomatic treatments
-Antcholinesterase agents
-pyridostigmine 30-60mg tds Maximum useful dose is
120 mg every 3–6 h during daytime
• Chronic immunomodulating treatments
-glucocorticoids
-and other immunosuppressive drugs
• Rituximab has recently been found to be effective in resistance case of
MG – evidence limited to case reports (Burusnukul et al dec 2010)

64. • Rapid immunomodulating treatments
– plasmapheresis
– intravenous immune globulin
• Surgical treatment (thymectomy)
-thymoma
-generalized myasthenia

65. Prognostic indicators
-Generalized disease
– Thymoma
– Involvement of the respiratory muscles with
impaired vital capacity

66. Way forward
• Started on pyridostigmine 60mg bid
• Prednisolone 60mg od(advised red 30mg , add low
weekly methotxt)
• Expensive 120,000
• Fares well, with Rx ,Off medication gets some remissions

67. • Hematenics
• Hyercholestemia - statins ?fibrates-
additional costs,advised on diet.
• Given the list of the medications that are likely
to worsen her disease.

68. Thanks