Transcript 9-myasthenia.ppsx

The skeletal muscles can be affected by
diseases affecting the muscle primarily as
myositis or muscular dystrophies or
secondarily due to systemic abnormality as
Hypocalcaemia and hypokalemia. Affection
of muscle is characterized by proximal
weakness , no reflex changes (except in
advanced muscle atrophy) ,no sensory
changes and no central signs.
Concept map
A 24 year old woman ----difficulty in walking not due to bone
;joint or vessel disease?
What do you thing about structure involved
NS???
What is localization? Type of weakness upper or lower?
Distal ----segmental --pyramidal---proximal
Go to the case history : it is affecting standing from sitting
position –climbing ;combing ;tired with cloak handling
specially at the end of the day with difficulty in swallowing ;
shaving in male?
So it is ----------what do you think ;the causes?
MOST LIKELY?----MG? define ;cause : pathology ; C/F ;
D; confirm D. ------Assessment specific and general ?
Myasthenia gravis
It is progressive fluctuant muscle fatigue affecting striated skeletal
muscle with predilection to affect proximal m. ,ocular ,bulbar and
respiratory m.
Onset : 2
early onset 15-35 which tend to affect female more than male .
late onset above 5o years which affect male more than female with
high incidence of thymoma.
Etiology and pathology:
is unknown but most accepted theory is an autoimmune mediated
process, Ach receptor antibody that block or lyses ACH receptors
at post junctional muscle membrane at NM junction? This is most
likely related to thymus gland abnormality which is seen in majority
of cases .15% they have thymoma with more incidence in late
onset MG and majority have thymus abnormality like
hyperplasia(70 -80%).
anti ACH recep. Ab positive in 80% of GMG and anti musk ab.
(muscle specific tyrosine kinase Ab) Positive in in 70% of ACH
receptor Ab negative patient.
There is increase in incidence of other A.I disorder like thyroid and
linked with certain HLA haplotype like B8&DRw3.
Some drug recognized to cause myasthenia like as
D-pencillamine which may ppt. antibody mediated
myasthenic syndrome, some drugs exacerbate the
disease and should be avoided in MG like
ciprofloxacin , succinylcholine, aminoglycoside
antibiotics, quinine, qunidine, and botulinum toxin).
In addition, bone marrow transplantation is
associated with the development of MG as part of
the chronic graft versus host disease.
With time the pathological changes include the
muscle itself that lead to irreversible damage at m.
membrane.
Clinical feature& diagnosis
60% of pt presented with ocular s. in form of diplopia or and
ptosis .the cardinal s. of abnormal m. fatigue and weakness
which is fluctuant.
weakness of m. of chewing and bulbar m. is common and resp.
m. also may involved (not uncommon cause of death)
especially in myasthenic crisis which should be differentiated
from cholinergic crisis, both needs ventilators support.
to confirm diagnosis we need to do
Tensilon test ? False positive?
EMG & NCS? Positive decremental test by using single mf EMG
,we got better results. What is Ptosis ice bag test?) related to
esterase enzyme
Other diagnostic tests are ACH Ab. assay found in 80% -90%
less frequently in ocular MG. antiskeletal m. Ab suggest
presence of thymoma.
two highly sensitive laboratory studies are single fiber EMG and acetylcholine receptor
antibodies; nonetheless, neither test is 100% sensitive.
All pt. needs to assess thymus gland by CT-scan more useful
than ordinary X-rays. Screen for other AI disease is of helps
especially thyroid disease.
Management
to maximize the activity of ACH at the remaining receptors
to abolish the immune attack at or on motor end plate
Symptomatic: by giving cholinesterase inhibitors CEI as
pyridostigmine (mestinon) 60mg 4-6 times daily depending on
response and severity ,or neostigmine 30 mg 2-3 hourly (short
acting) .the muscarinic SE as salivation and diarrhea and colic can
be overcome by giving propanthilline. over dose of CEI can cause
cholinergic crisis, salivation and small pupil (paralysis ,muscle
fasciculation ,pallor & sweating )
Disease modifying therapy:
Thymectomy: should be done as early as possible in any Ab –
positive where the disease not confined to ocular muscle unless the
disease has been established >7 years. Also IN THYMOMA
Plasma exchange? Useful as transient line in case of m. crisis or preoperative.
IV immunoglobulin ?alternative to P. exchange
Steroid: improvement is common after transient deterioration and
treatment should given in the hospital. treatment continue for
months or years resulting in SE.
Other immunosuppressant treatment : azothioprim 2.5 mg /kg daily
PROGNOSIS: ocular ; no indication for thymectomy
antisense oligonucleotides(synthetically manufactured
short segments of deoxynucleotide sequences that
cause targeted gene transcription inhibition, designed
to interact with their specific complementary mRNA,
thereby interfering with transcript stability and/or
translation).
EN101 antisense (Monarsen) acts against production
of AChE and has been tested in Israel
Muscular dystrophies? Inherited
Muscular dystrophies? Inherited
group of mf disease characterized by slow progressive
weakness, selectivity of muscles group, family history and
genetic markers as skeletal deformity.
The most common is:
Duchene MD which is sex linked affecting males and female is
carrier
Starts early ,2-3 years with difficulty in walking and any be
earlier ,progressed over years render the pt. wheel chaired at
age of 10 years ,death occur usually 10 years after diagnosis
because of cardiomyopathy as an association and respiratory
muscle affection and infection.
clinically the child have proximal M. weakness with calf m. hyper
atrophy secondary to fat replacement for disintegrated MF;
CPK is very high with EMG finding is that of myopathy and
muscle biopsy for histochemistory is diagnostic,
treatment is supportive. Gene therapy in trial. Steroid may be
given with controversial results.
OTHERS:
Baker MD ,limb girdle , facioscapular , distal type , ocular.
Myotonia?
Myotonia?
Myotonia is a skeletal muscle disorder characterized by excessive electrical
irritability of sarcolemma .
Clinically it causes muscle stiffness that typically worsen with cold .
On examination it is frequently possible to demonstrate M. by difficulty in
relaxing the hand after sustained grip or persistent contraction after
percussion of the belly of muscle; cataract , HT ,hypgonadism ,
cardiomyopathy----are associated features
Electrophysiological assessment by EMG study is often showing long bursts
of muscle F. action potential following discrete stimuli such as percussion
of M. (typical sound of a dive bomber).
IT is important to divide M clinically in Dystrophic type and non dystrophic
Myotonia dystrophy / myotonin CHR. 19
(protein kinase)
Myotonia Congenita? Non-dystrophic type
Myotonia Congenita is an autosomal dominant or autosomal
recessive inherited neuromuscular disorder characterized by the
inability of muscles to quickly relax after a voluntary contraction. The
condition is present since early childhood, but symptoms can be mild.
Most children will be 2 or 3 years old when parents first notice their
muscle stiffness, particularly in the legs, often provoked by sudden
activity after rest. The disease doesn’t cause muscle wasting ; in fact,
it may cause muscle enlargement. Muscle strength is increased.
There are two forms of the disorder: Becker-type, which is the most
common form; and Thomsen’s disease, which is a rare and milder
form. The disorder is cause by mutations in a gene responsible for