Muscle Diseases
Muscular Dystrophy
X-linked recessive
Duchenne type muscular dystrophy (DMD)
Becker type muscular dystrophy (BMD)
Autosomal Dominant Inheritance
Myotonic dystrophy (DM)
Fascioscapulohumeral dystrophy (FSHD)
Oculopharyngeal muscular dystrophy (OFMD)
Autosomal Recessive Inheritance
Limb-girdle dystrophy
Fasioscapulohumeral Dystrophy
It is autosomal dominant.
There is weakness in the lower half of the face, trapezius, pectoral and humeral muscles.
The clinical course is slow.
It is one of the muscle diseases with the best prognosis.
Limb-girdle Dystrophy
It can start at any age between the second and sixth decades.
Involves only proximal muscles.
Starts from The pelvic girdle muscles.
It is one of the muscle diseases with the best prognosis.
Limb-girdle OR is the only muscle disease with transition.
Myotonic Dystrophy
It is autosomal dominant.
The contracted muscle cannot relax (action myotonia).
It occurs at the age of 40-SO, has a typical facial appearance.
Frontal baldness, ptosis, low chin, sunken cheek, atrophy of neck and shoulder girdle muscles.
80% of cases have cataracts.
There is testicular atrophy, diabetes.
There is weakness and atrophy in the distal extremities.
Neuromuscular Junction Diseases
Myasthenia Gravis
• It is an autoimmune disease characterized by muscle weakness that increases with movement, mostly targeting postsynaptic nicotinic acetylcholine receptors (AChR).
• It is a disease with a very high mortality due to respiratory crisis.
• The most important feature of the disease is muscle weakness, which increases with fatigue and improves with rest.
• The disease often begins with ocular symptoms, most often with ptosis.
• Bulbar symptoms include difficulty in speaking, swallowing and chewing, and difficulty in breathing in the most severe form of the disease.
• The thymus is abnormal in almost all cases. There is thymus hyperplasia.
According to the muscles involved
Generalized
Eyepieces
By starting age
Early (before age 40 or 50)
Late (After 40 or 50 years old)
by antibody
Anti-AChR positive
Anti-MuSK positive
Seronegative
Up to 85% of patients with generalized MG have anti-AChR antibodies in their serum. Anti-MuSK (anti-muscle specific kinase) antibodies are found in up to half of the patients (15%) without this antibody. An antibody has not yet been detected in the remaining small part of the patients, this group is called "seronegative MG".
Muscle-specific tyrosine kinase myasthenia
Increased muscle-specific tyrosine kinase antibodies (anti-MuSK)
Respiratory failure is more common.
EMG as in Myasthenia graves.
No thymus hyperplasia, no thymoma.
Responds to steroids.
Neonatal myasthenia
It is caused by maternally transmitted antibodies.
Days improve within weeks.
Congenital myasthenic syndromes
Congenital myasthenic syndromes (CMSs) are a group of hereditary diseases of the neuromuscular junction.
Since CMS is not immunological, there is no antibody in the serum and there is no response to immunological treatment.
These diseases usually present with weakness in the ocular, bulbar and extremity muscles in the first year of life.
CMS may be due to a presynaptic, synaptic or postsynaptic pathology.
Usually in the first 3 months, it is noted that the child cries in a low voice and cannot suckle well, then ptosis is noticed.
Congenital Myasthenic Syndromes
• Postsynaptic
• AChR deficiency
• Kinetic anomalies (slow channel, fast channel)
• Lack of rapsin
• DOK7 deficiency
• Synaptic
• Endplate AChE deficiency
• Presynaptic
• Choline acetyltransferase deficiency
myasthenia caused by drugs
Penicillamine therapy
The antibody disappears when the drug is discontinued.
symptoms
It has three characteristic findings:
1. Variable muscle weakness undulating during the day (not in other diseases)
2. It is characteristic that it starts from the eyes, ptosis and diplopia
3. There is a clinical response to cholinergic drugs.
Ach receptor antibody titers are lower in ocular myasthenia.
EMG findings may be normal in ocular myasthenia.
Results
No deterioration in vital signs
Eyelid drooping
Limitation of conjugated gaze due to weakening of the eye muscles
Ophthalmoplegia in one or both eyes
Weakness in arm, leg, oropharyngeal and respiratory muscles
No fasciculation, sensation is normal, reflexes are preserved (even if the muscles are weak)
Pupillary response is not impaired, no internuclear ophthalmoplegia
Drugs that myasthenia patients cannot use
Aminoglycosides
Quinolones
Polymyxin-B
Tetracycline
in diagnosis
Significant improvement with edrophonium test
Ach receptor antibody makes 90% diagnosis in generalized myasthenia.
Reduction in muscle action potentials in repetitive nerve stimulations, 90% diagnostic
Offer EMG
Presence of thymoma
in treatment
Anticholinesterase drugs should be started when the diagnosis is made. Pridostigmine is the most popular
Thymectomy (it is very useful even if it is not a thymoma)
Steroid, plasmapheresis, IVIG
Eaton-Lambert Syndrome
• It is a paraneoplastic syndrome. It is most common in lung small cell carcinoma.
• Autoantibody formation against presynaptic Ca++ channels
• Extraocular muscles are rarely involved.
• EMG to differentiate between Eaton-Lambert syndrome and myasthenia gravis
In Eaton-Lambert syndrome, action potential amplitude increases after the first stimulus.
Action potential amplitude a DECREASES after the first stimulus in M.gravis
Mitochondrial Diseases
0 Mitochondrial diseases are usually multisystemic diseases that do not only concern the muscle tissue and go with mitochondrial dysfunction.
In hereditary ones, genetic transmission occurs according to Mendelian laws, that is, due to nuclear gene defects or by maternal transmission of mitochondrial DNA defects.
Because the mitochondria is the most important energy store of the cell, an energy deficit occurs.
Therefore, the most frequently affected tissues are skeletal muscle, smooth muscle and cardiac muscle, retina and brain tissues, which need the most energy.
0 Well-defined mitochondrial syndromes:
MELAS: Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes
MERRF: Myoclonic epilepsy, “ragged red” fibers
CPEO: Chronic progressive external ophthalmoplegia
MNGIE: Myo-neuro-gastrointestinal syndrome, encephalopathy
NARP: Neuropathy, ataxia, retinitis pigmentosa
Leigh syndrome
Kearns Sayre syndrome
0 Ptosis and ophthalmoplegia are common findings in the best-defined mitochondrial diseases. Muscle weakness can be of varying degrees.
0 Exercise fatigue can be present even in the background.
0 Serum CK level is mostly normal, sometimes slightly elevated.
0 EMG can be normal or myopathic.
0 The presence of "ragged red" fibers (RRF) in muscle biopsy, the presence of mitochondrial aggregates by enzyme histochemistry, or the absence of cytocrum oxidase production help to identify this group of diseases in general.
0 In the ischemic exercise test, the serum lactate level is much higher than normal.