Neuromuscular Disorders: Key Differences

• Motor function disorders are covered in two parts

General Organization of the Motor System

• There are three primary levels:
• The cerebral cortex and basal ganglia form the first level
• The brain stem and cerebellum are the second
• The spinal cord is the third

General Organization in Motor Function

• The upper motor neuron system receives input from the basal ganglia and cerebellum
• The reticulospinal, rubrospinal, and vestibulospinal tracts have influence over the lower motor neuron system

Injury to Motor Neurons

• Motor neuron injuries include
• Upper motor neuron injury (UMN)
• Lower motor neuron injury
• Injury of peripheral nerves
• Disorders of the neuromuscular junction
• Disorders of the skeletal muscles

Voluntary Movements

• Voluntary movements, balance, and position are controlled by the motor cortex via several pathways
• Corticospinal tract
• Red nucleus
• Reticular nuclei
• Superior colliculus and vestibular nuclei

Corticospinal Tract

• The corticospinal tract consists of upper and lower motor neurons
• Two types of corticospinal tracts:
• Medial: Signals travel via an interneuron
• Lateral Tract: Signals travel directly to motoneuron

Somatotopic Projection

• The motor cortex contains a motor homunculus representing body parts

UMN vs LMN Lesions

• UMN lesions involve groups of muscles, hypertonia, hyperrreflexia, little to no atrophy, and no fasciculation
• LMN lesions involve separate muscles, hypotonia, hyporeflexia, marked atrophy, and possible fasciculation

Upper Motor Neuron Disorders

• Paralysis = loss of movement
• Paresis = weakness and partial flexing, resulting in lost muscle strength
• Fasciculation = involuntary contractions of separate muscle fibers

Hyperreflexia in UMN Injury

• Spinal shock occurs due to cessation of supraspinal innervation of alpha-motoneurons
• Reduced supraspinal activation of alpha-motoneurons affects antigravity muscles
• Partial denervation of alpha/gamma-motoneurons and interneurons leads to increased sensitivity of these neurons
• The reflexes will gradually gain a stronger influence, leading to hyperreflexia

Spasticity in UMN Injury

• After loss of the descending tracts functions, the activity of the alpha-motoneurons come under the increasing influence of muscle spindles and Golgi tendon organs.
• Stretching the spindles will stimulate the alpha motoneurons of the same muscle via a monosynaptic reflex
• An increased influence of the muscle spindles results in massive contraction on stretching

Pyramidal Tract Injury

• Injury to the left internal capsule may cause hemiparesis on the right

UMN Injury: Babinski Symptom

• UMN injuries may result in an extensor plantar response, also known as the Babinski sign

Upper Motor Neuron Injury

• Diseases associated with UMN injury:
• Stroke caused by bleeding or ischemia
• Primary lateral sclerosis (PLS): A rare neuromuscular disease that affects only upper motor neurons, leading to gradual lower extremity stiffness and pain
• Progressive bulbar palsy (PBP): A disease that attacks the cranial nerves, causing degeneration of motor neurons in the cerebral cortex, spinal cord, brain stem, pyramidal tracts and specifically affects CN IX, X, and XII
• Multiple sclerosis: Demyelination CNS disease that can cause muscle weakness, hyperreflexia, Babinski sign and sensory disorders, usually starts between 20-40 years of age and affects women more often than men,
• Pseudobulbar palsy: an inability to control facial movements and may cause uncontrolled emotional outbursts. It's caused by bilateral damage to corticobulbar pathways

Lower Motor Neuron Injury

• UMN injury may occur alongside LMN injury

Motor Unit

• A motor unit includes a motor neuron, all of the skeletal muscle fibers the neuron innervates, the neuromuscular junctions, and axon terminals
• Damage to a lower motor neuron eliminates voluntary and reflex control over the innervated motor unit

Lower Motor Neuron Injury

• Diseases associated with LMN injury:
• Progressive muscular atrophy (PMA): Also called Duchenne-Aran disease, is due to degeneration of lower motor neurons in the spinal cord, and causes muscle weakness, atrophy, and fasciculation
• Bulbar palsy: Refers to signs and symptoms related to impairment of function of glossopharyngeal nerve (IX), vagus nerve (X), the accessory nerve (XI), and the hypoglossal nerve (XII), and is caused by a LMN lesion in the medulla oblongata
• Poliomyelitis: A virus infection or injury of the anterior horn in the spinal cord

Upper and Lower Motor Neuron Injury

• Lateral Amyotrophic Sclerosis:
• Morbidity is 1-2/100000 popul/year, affecting 55-60 year olds and affecting men two times as often
• The death of both upper and lower motor neurons
• Leads to skeletal muscle/motor cortex atrophy, sclerosis of the corticospinal/bulbar tracts, thinning of the hypoglossal nerves, and thinning of the anterior roots of the spinal cord.
• Inclusion bodies of protein, known as Bunina bodies, may be present in the cytoplasm of motor neurons

Peripheral Nerves Injury

• Mononeuropathies: Trauma, compression, and infection
• Tunnel-carpal syndrome is caused by repetitive movements and systemic diseases, and causes pain, sensory disturbances, and weakness
• Polyneuropathies: Multiple demyelination or axonal degeneration, accompanied by symmetrical sensory, motor or mixed sensorimotor impairment, that's caused by immune diseases, toxins and metabolic diseases
• Includes Guillain-Barre syndrome, which is acute inflammatory polyneuropathy

Carpal-Tunnel Syndrome

• Symptoms include numbness and tingling in the thumb, index, middle finger, and half of the ring finger
• Muscles at the base of the thumb may atrophy

Disorders of Neuromuscular Junction

• Also a type of motor neuron damage

Injury of Neuromuscular Junction

Diseases associated with neuromuscular junctions that result in injury:

• Curare-type drugs: inhibit depolarization and block Ach receptors at the postsynaptic membrane
• Physostigmine, neostigmine: inhibit the action of acetylcholinesterase
• Used to treat anticholinergic poisoning from atropine, scopolamine, and other anticholinergic drug overdoses
• Botulinum toxins: inhibit the release of Ach
• Organiophosphates (insecticides): bind and inhibid acetylcholinesterase
• Myasthenia gravis: causes ACh receptor loss via auto Abs
• Results in complement-mediated damage to the postsynaptic membrane.
• Lambert-Eaton syndrome: a rare autoimmune disorder characterized by muscle weakness of the limbs, occurring in around 60% of cases

Miastenia Gravis

• Clinical features include muscle weakness, affecting the eyes initially, and later breathing

Disorders of Skeletal Muscles

Skeletal Muscle Injury

• Types of skeletal muscle injuries:
• Muscle atrophy: lack of muscle innervation (denervative atrophy) Muscular dystrophy – genetic diseases that cause progressive deterioration of muscle function due to mixed hypertrophy, atrophy and necrosis of muscle cells
• Primary muscle disease in which the nervous system is not affected Fatty and connective tissue replaces muscle fibers and pseudohypertrophy develops
• Duchenne Muscular Dystrophy: most common type, X-linked and from a male mother to a newborn
• Becker Muscular Dystrophy: X-linked, slowly progressive

Duchenne Syndrome

• Clinical manifestations include:
• Onset between age 3-6
• Progressive muscle weakness, beginning with the legs and pelvis
• Pseudohypertrophy in calf muscles
• Cardiopulmonary involvement Mild - moderate MR Symptoms include the shoulders and arms being held back awkwardly when walking, swayback, weak belly muscles (child is poor at sit-ups), thin, weak thighs, poor balance, thick lower leg muscles, a tight heel cord (contracture), with the child walking on toes, and weak muscles in front of the leg causing foot drop

Differential Diagnosis of Weakness

• Lists conditions for which weakness is a diagnostic sign and categorizes them by genetic, inflammatory, infectious etc

Explore the differences between Lambert-Eaton syndrome and Myasthenia Gravis. Questions cover the action of organophosphates and botulinum toxin on muscles. Also includes a question about Duchenne muscular dystrophy.