General Information about Neuromuscular Diseases
• Generally, myopathies have a proximal distribution of muscle weakness and wasting (except for myotonic muscular dystrophy), while the distribution of neuropathies is usually distal (excluding spinal muscular atrophy). Deep tendon reflexes are usually lost in neuropathies and motor neuron diseases. In myopathies, however, it is preserved, albeit decreased. Sensory abnormalities suggest neuropathy. In addition, undescended testis can also be seen in many congenital neuromuscular diseases, including spinal muscular atrophy, myotonic muscular dystrophy, and congenital myopathies.
Diagnosis of Neuromuscular Diseases
• Electromyography (EMG): based on the principle of inserting a needle into a muscle and measuring electrical potentials in various contraction states.
It distinguishes between denervation defect and myopathy.
Cannot identify the specific type of myopathies,
Can identify myotonia, spontaneous activation is continuous
There is no electrical activity in the normal axis at rest, fibrillation is seen in anterior horn motor diseases
Look at the rate of fatigue with repetitive stimuli, tetany if the contraction is continuous, myasthenia if it disappears rapidly In peripheral nerve diseases, the conduction speed decreases.
• Electrocardiography (ECG): If myopathy is suspected, cardiac evaluation is important. Because the heart is involved in muscular dystrophies and inflammatory metabolic myopathies. The ECG usually detects cardiomyopathy or conduction defects that are clinically asymptomatic.
• Muscle biopsy: Muscle biopsy is very important for diagnosis, unless the definitive diagnosis of diseases affecting muscle structure can be obtained by molecular genetic tests from blood. The specific and most important diagnostic study for most neuromuscular disorders is muscle biopsy.
Not only can neurogenic and myopathic processes be distinguished, but the type of myopathic and specific enzymatic defects can also be determined.
The most frequently sampled muscle is the vastus lateralis (quadriceps femoris). The deltoid muscle should not be used in the biopsy.
Immunohistochemical examination is required in some cases, such as demonstrating dystrophy in cases of suspected Duchenne muscular dystrophy or merosin in congenital muscular dystrophy.
Distribution of neuromotor diseases
Proximal Muscle Weakness
• dystrophy
• Duchenne muscular dystrophy
• Limb-Girdle muscular dystrophy
• Dermatomyositis, polymyositis
• Kugelberg-Welander disease (late-onset spinal muscular atrophy)
Distal Extremity Weakness
• Polyneuropathy (Guillain-Barre syndrome, others)
• KMDN I (hereditary Motor-Sensory Neuropathy) (Charcoat Marie-Tooth disease)
• KMDN II
• Myotonic dystrophy
• Distal myopathy
Ophthalmoplegia and Extremity Weakness
• Myasthenia gravis
• Botulism
• Myotonic dystrophy
• Congenital structural myopathy
• Miller Fisher variant of Guillain-Barre syndrome
Facial and Bulbar Weakness
• Myasthenia gravis
• Botulism
• Poliomyelitis
Spinal Muscular Atrophy (SMA)
• It is a disease characterized by progressive muscle weakness due to loss of anterior horn cells of the spinal cord.
• It is the most common cause of infant death among autosomal recessive diseases.
• Most patients are inherited autosomal recessively, there are those with X-linked or OD inheritance. The disease occurs as a result of mutations in the SMN (Survival Motor Neuron) gene located in Exon 7 on the long arm of the 5th chromosome.
• The SMN protein SMN1 is produced due to two genes called SMN2. SMN1 gene mutation is present in 98% of cases. As a result of the mutation in the SMN1 gene, SMN2 tries to compensate for protein synthesis, but fails. Mild forms of SMA have more than 2 copies of the SMN2 gene, while late-onset SMA has 4 copies of SMN2.
• It is the second most common neuromuscular disease after Duchenne muscular dystrophy.
• Extraocular, urethral and anal sphincter muscles are preserved.
• Serum creatine kinase (CK) level is normal or slightly increased.
• The ribs are quite thin on the chest X-ray. EKG, especially II. It is typical to see tremor at baseline in the lead. This tremor seen on the EKG occurs secondary to muscle fibrillations.
• There is regular spontaneous motor unit activity in EMG. A normal nerve conduction velocity excludes motor neuropathy.
• Group atrophy of type 1 and type 2 muscle fibrils is seen in muscle biopsy. There is no glycogen and lipid storage. The disease is divided into types according to the age of onset and the degree of loss of muscle function.
• Treatment is usually supportive therapy. Valproic acid, gabapentin and oral phenylbutyrate can be used in the treatment considering that they slow down the progression of the disease by increasing SMN2 activity. In addition, it is aimed to increase SMN2 activity and slow down the progression of the disease with the intrathecal application of the drug Nusinersen.
SMA Type 1 (Werdnig-Hoffman Disease) (Severe Infantile Form)
• Symptoms begin at birth or in the first months.
• It is an important feature to have very little fetal movements in the mother's womb. Arthrogryposis, congenital contractures may be seen.
• Sucking and swallowing functions are impaired.
• Muscle weakness is symmetrical. Ocular movements and diaphragm are preserved.
• Cardiac functions are normal.
• Tongue fasciculation is common.
• There is abdominal breathing.
• Intelligence is normal.
• More than 65% of patients die before the age of 2.
SMA Type 2 (Late Infantile, Slow Progressive Form)
• Symptoms usually appear after 6 months.
• It is noteworthy that the baby cannot sit without support in the 9-12th months or cannot walk at the age of 1 year.
• Tremor is seen in the fingers, perception functions and sensory functions are normal.
• 70% of all tendon reflexes are lost.
• There is a delay in motor functions.
• Nasone speaking, scoliosis, malnutrition due to gastroesophageal reflux and aspiration pneumonia are seen in living patients.
SMA Type 3 (Kugelberg-Welander Disease)(Chronic, Juvenile Form)
• It is the mildest form and infants may appear normal.
• May begin to walk, but is characterized by frequent falls.
• Proximal limb weakness, legs are more affected.
• There is loss of DTR, sensation is normal.
