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 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%). 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 pre- operative. 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

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 shutting off electrical excitation in the muscles. autosomal dominantautosomal recessiveautosomal dominantautosomal recessive