A rare case of BULBAR MYASTHENIA after 7 yrs of THYMECTOMY

1. Bulbar Myasthenia after 7
yrs of Thymectomy
Dr.Panneer.A Unit
Presenter: Dr.M.Ramesh Babu

2. History
A49 yrs female presented with complaints of
change in voice since 1 month - her voice felt
"horrible and nasty" and that she could not speak
loudly and had difficulty being understood by
others.
The main vocal aspects indicated by the patient
were vocal fatigue, hoarseness, voice failure,
vocal tremor, and the need to make an effort to
speak.
Symptoms are more at the end of the day and
feels better in early morning .

3. No H/O difficulty in chewing, swallowing, no
respiratory difficulty
No H/O difficulty or heaviness in opening her
eyes, diplopia, weakness in neck muscles.
No H/O fatiguability in walking or in daily
activities.

4. Past History: H/O Total thymectomy done in 2010,
where identified by routine health screening. Post
Thymectomy - No complaints
HPE Report - Nodular sheets and proliferation of
monomorphic lymphoid cells separated by wide
bands of fibrocollagenous tissue. The lymphoid
cells appear hyper chromatic nuclei . Mitosis is low.
F/S/O - Low grade Thymoma.
H/O Hypothyroidism - since 6yrs on treatment

5. General Physical Examination
Patient moderately built and nourished
Vitals : H.R- 88/min, B.P- 130/80 mmhg
Voice fatiguabity +
Nasal Twang +
Single breath count- 56
CNS Examination- Normal
Other Systemic examination - Normal

6. Investigations
Bed side Test- Neostigmine test- positive
RNS - Showed decremental positivity
Anti Ach R - Strongly positive (87nmol/l)
HRCT- Normal
Thyroid profile- WNL

7. Audios

8. Myasthenia Gravis
• Myasthenia Gravis (MG) is a neuromuscular
disorder characterized by weakness and
fatigability of skeletal muscles.
• Key Concept :-
It is due to the decrease in the number of
available acetylcholine receptors (AchRs) at
neuromuscular junctions due to antibody mediated
autoimmune attack.

9. Pathophysiology
• Autoimmune channelopathy
• Genetic predisposition:
• HLA B8 & DR3
• DR1 specific for ocular myasthenia
• 75% patients have abnormality of thymus
• 10% have Thymoma Autoantibodies against nicotinic
acetylcholinrereceptors (nAchRs)
• These antibodies prevent binding of Ach to its receptors
• Other action:
• Destruction of receptors
• By complement activation
• Elimination by endocytosis

11. Pathophysiology

13. Anti–acetylcholine receptor antibody
• The anti AChR antibody test is reliable for diagnosing
autoimmune MG.
• It is highly specific (as high as 100%, according to Padua
et al). [4]
• Results are positive in as many as 90% of patients who
have generalized MG but in only 50-70% of those who
have only ocular MG; thus false negatives are common in
cases of purely ocular MG.
• False-positive anti-AChR Ab test results have been
reported in cases of thymoma without MG and in patients
with Lambert-Eaton myasthenic syndrome, small cell lung
cancer, or rheumatoid arthritis treated with penicillamine,
as well as in 1-3% of the population older than 70 years.

14. Tindall reported AChR Ab results and mean Ab
titers in a group of patients with MG
Data suggest a trend toward higher Ab titers in
more severe disease, though the titer does not
predict severity in an individual patient.
Changes in the anti-AChR titer correlate with long-
term improvement induced by prednisone or
azathioprine; the same changes are not observed
consistently in patients who undergo thymectomy.
However, this finding is not consistent, and serial
Ab titers alone are not reliable.

15. Anti-MuSK antibody•About half of the patients with negative results for anti-AChR
Ab (seronegative MG) may have positive test results for
antibody to muscle-specific kinase (MuSK), a receptor
tyrosine kinase that is essential for neuromuscular junction
development. [26]
•These patients may represent a distinct group of autoimmune
MG, in that they show some collective characteristics that are
different from those of anti-AChR–positive patients. [27]
•Anti-MuSK–positive individuals tend to have more
pronounced bulbar weakness and may have tongue and facial
atrophy. They may have neck, shoulder and respiratory
involvement without ocular weakness.
•They are also less likely to respond to acetylcholine esterase
(AChE) inhibitors, and their symptoms may actually worsen

16. Anti-lipoprotein-related protein 4 (LRP4)
antibody
•Lipoprotein-related protein 4 is present on the
postsynaptic membrane and is a receptor for agrin and
is essential for neuromuscular junction formation.
Antibody to this protein is present in 2-27% of double
seronegative myasthenics (absence of AChR and Anti-
MuSK antobodies) [30] .

17. Antistriational antibody
• Serum from some patients with MG possesses antibodies
that bind in a cross-striational pattern to skeletal and heart
muscle tissue sections. These antibodies react with
epitopes on the muscle protein titin and ryanodine
receptors (RyR).
• Almost all patients with thymoma and MG, as well as half of
the late-onset MG patients (onset at 50 years or later),
manifest a broad striational antibody response.
• Striational antibodies are rarely found in anti-AChR–
negative patients.
• They can be used as prognostic determinants in MG; as in
all subgroups of MG, higher antibody titers are associated
with more severe disease. [31]
• Because of a frequent association with thymoma, the

18. Anti–striated muscle antibody
•Anti-SM Ab is present in about 84% of patients with
thymoma who are younger than 40 years and less often
in those without thymoma.
•Positive test result should prompt a search for thymoma
in patients younger than 40 years.
•In individuals older than 40 years, anti-SM Ab can be
present without thymoma.

19. Discussion
Thymus plays a key role in the immunologic status of an
individual, and disease of the thymus can be associated with
autoimmune disorders.
Thymus is abnormal in ~75% of patients with MG
In ~65% the thymus is "hyperplastic,"
(a nonneoplastic lymphofollicular hyperplasia of the thymic
medulla) with the presence of active germinal centers
detected histologically
• 10% of patients have thymic tumors (“ neoplastic”)
• Thymomas with malignant characteristics may spread locally
• Upon distant spread, the lungs and liver are usually affected.

20. Pathogenic Mechanism of PTMG
Current hypothesis of the pathogenic mechanism of PTMG
includes:
Thymoma recurrence
Surgical exposure to larval MG and
Activation of peripheral lymphocytes from thymoma after surgery.
Muscle-like cells within the thymus (myoid cells) which bear AChRs
on their surface may trigger immune response first appearing many
years following the removal of a thymoma reportedly occurs in 1.5-
28% of cases.
Hoffacker V, Schultz A, Tiesinga JJ, Gold R, Schalke B, Nix W, et al. Thymomas after the T-cell subset composition in the blood: a potential
mechanism for thymoma associated autoimmune disease. Blood 2000;96:3872-3879

21. The interval between a thymectomy and the onset
of postoperative MG has varied between studies.
Two of the studies involving an adequate number of
cases and obtaining detailed clinical data found that
the mean interval between thymectomy and the
onset of postoperative MG was 19 and 18 months.
Namba et al. reported that patients with a shorter
onset of postoperative MG had a better prognosis,
but other study did not find this relationship.3,8 rarity
of postoperative MG cases has meant that it
remains unclear whether the interval between
thymectomy and the onset of postoperative MG
influences the prognosis.

22. This discrepancy may be due to different
therapies being applied for MG.
Most reports demonstrate that postoperative MG
responds to anticholinesterase drugs and/or
steroids, and that the prognosis is relatively
good.5,8
Although a thymectomy does not prevent the
onset of postoperative MG, this procedure is
associated with a good prognosis.

23. In the study of Kondo and Monden, the anti-
AChR antibody at onset varied between 1.8 and
91 nmol/l.8 The majority of patients show a
clinical severity of type I or type IIA on
Osserman's classification. However, they found
that the titer of anti-AChR antibody did not
correlate with clinical severity, as was the case
in our patient.

24. The mechanism underlying the onset of postoperative MG is
unclear.
The various time periods between a thymectomy and the
onset of postoperative MG raise doubts as to whether a
thymectomy directly triggers MG onset.
Two useful studies were recently published. Hoffacker et al.
found using T-cell-proliferation assays for a fragment of the
AChR that the thymoma released mature auto-antigen-
specific T-cells into the periphery.9 Buckley et al. found that T-
cells in a thymoma were exported to the peripheral blood, and
that these T-cells could persist in the periphery for many
years.10
These studies suggest that a thymoma actively exports large
numbers of mature T-cells into the peripheral blood, with
these cells persisting in the periphery, potentially stimulating
autoantibody production and subsequent autoimmune
disease.

25. The late onset of MG and other autoimmune
disorders should be kept in mind as possible
complications of surgical treatment for thymoma.
Therefore postoperative follow-up care with
consideration of postoperative MG is necessary
after resecting a thymoma.
In postoperative MG cases, recurrent or
metastatic thymoma should be ruled out
because reoperation can be effective even in the
treatment of MG.

26. Can Vaccine trigger or worsen
Myasthenia?
There is no convincing evidence that any vaccination affects
MG symptoms in any way.
It is well known that episodes of infection can bring on
myasthenia crises.
Since vaccination help to prevent some of these infections, it
seems for patients with myasthenia to have them appropriate.
MG by itself does not affect vaccination , so these warnings only
concern people on immunosuppressive treatments.
These patients should remember to always mention this before
they are given vaccines .
A good rule of thumb is that live attenuated should be avoided ,
while others are safe.

27. Thank You