Disorders of the Motor Unit

Question 1

Damage can occur at ___ _____ of the motor unit:

Answer 1

any level

• Muscle
• Neuromuscular junction
• Nerve axon (efferent)
• Motor neurons
  
  • Lower MNs in spinal cord
  • Upper MNs in brainstem and cortex

Question 2

Definition:

Myopathic diseases

Answer 2

Diseases arising from intrinsic abnormalities in the skeletal muscle

• Example: Duchenne muscular dystrophy

Question 3

Definition:

Neuropathic (Neuropathy):

Answer 3

Diseases that cause abnormalities in peripheral nerves

• Sensory afferent and/or motor efferent nerves
• Sensory and motor symptoms are more pronounced distally than proximally
  
  • Disease magnitude is proportional to length of the nerve

Question 4

Definition:

Neurogenic

Answer 4

Disease that interrupts normal innervation of muscle

• Denervation or reinnervation of muscle
• Abnormality in muscle is secondary to abnormality in the nerve innervating the muscle

Question 5

Muscular dystrophies (MD):

Answer 5

• Chronic, hereditary diseases
  
  • All inherited
• Symptoms are caused by muscle weakness
• Weakness progressively becomes more severe
  
  • Degeneration of muscles

Question 6

Muscular dystrophies (MD):

4 Major Types

Answer 6

1. Duchenne’s MD: Most common in children
   
   • _​​_Wasting, weakness in pelvic muscles
2. Facioscapulohumeral: Affects face and shoulder girdle
3. Myotonic dystrophy: Most common form in adults
   
   • Inability to relax muscles
   • After strong contraction, especially in hands.
4. Limb-girdle MD: Proximal muscles in pelvic and shoulder girdle are affected

Question 7

Duchenne’s MD:

Answer 7

• Most common muscular dystrophy that affects children
• X-linked, recessive inheritance: Males offspring are affected, but females may be carriers

Question 8

Duchenne’s MD:

Onset:

Answer 8

• **Onset: **usually when boy beings to walk
  
  • disease progresses with age
  • death 20-30 from respiratory complications

Question 9

Duchenne’s MD:

Clinical Symptoms

Answer 9

1. ​Waddling or lurching gait
   
   • abnormal walk/run
2. Muscle wasting, weakness
   
   • pelvic girdle muscles
3. Lordosis (forward curve of lower back due to weak back muscles)
4. Severe skeletal deformities
5. Scoliosis (curvature of spine)
6. Contractures (static muscle shortening)
7. Gastrocnemius muscle shortens so calf muscle appears enlarged

Question 10

Duchenne’s MD:

Cause:

Answer 10

• Lack of gene for dystrophin
  
  • located on X-chromosome.
• Boys with Duchenne’s MD have less than 5% of normal amount of dystrophin protein
• Dystrophin is a protein in the cytoskeleton of the muscle membrane:
  
  • Anchors actin in cytoskeleton to membrane
  • Stabilizes sarcolemma
• Without dystrophin:
  
  • sarcolemma membrane is unstable
  • shearing/tearing of membrane occurs
  • influx of Ca²⁺
  • necrosis of muscle fibers.

Question 11

How is Duchenne MD diagnosed?

Answer 11

• Gowers maneuver diagnostic test:
  
  • push up from the ground very slowly
• High creatine kinase levels in blood
  
  • CK normally in muscle
  • Leaks out of damaged muscle cells
  • CK Levels are elevated before clinical signs are present

Question 12

Diseases of the Neuromuscular Junction:

Answer 12

Myasthenia Gravis:

• Two forms
  
  • autoimmune form (prevalent)

Question 13

Myasthenia Gravis:

Pathophysiology

Answer 13

• Autoimmune disorder that impairs transmission at the NMJ synapse
• Antibodies are made against the Nicotinic Acetylcholine receptor in muscle:
  
  1. Antibodies bind to Ach receptor ⇒ Block Ach receptor from functioning
  2. Antibody binding cross-links Ach receptors and triggers internalization and
     degradation of receptor ⇒ Reduced number of Ach receptors
  3. Reduced junctional fold size, larger synaptic cleft space, diffusion of Ach from cleft

Question 14

What is the consequence of reduced Ach receptors caused by Myasthenia Gravis?

Answer 14

• Reduced number of functional Ach receptors:
  ⇒ Reduced amplitude of end-plate potentials
  ⇒ Action potential fails to fire in some muscles
  ⇒ Ach depletes with repeated firing
• Net effect: Muscle power is reduced when fewer muscle fibers contract
• Fatigue, weakness occur because Ach is depleted

Question 15

Myasthenia Gravis:

Clinical Symptoms

Answer 15

• Weakness and fatigue in cranial muscles, eyelids, eye muscles, ptosis (drooping of eyelids)
• Weakness and fatigue in oropharyngeal muscles, speech difficulty, slurring, difficulty chewing
• Respiratory muscles fatigue, difficulty breathing
  
  • may require mechanical ventilation
• Limb muscles may be affected, unstable or waddling gait, weakness in arms, hands
• Severity varies over day and from day to day
• Symptoms are usually worse at end of day or after exercise, symptoms relieved by rest

Question 16

What is the role of the thymus in Myasthenia Gravis?

Answer 16

• Patients with myasthenia gravis have tumors in thymus
• Lymphocytes in thymus produce antibodies against Ach receptor
• Myoid cells in thymus express Ach receptors and are antigenic
• Thymectomy: 50% of patients go into remission

Question 17

Myasthenia Gravis:

Treatment

Answer 17

• Acetylcholinesterase inhibitors
  
  • Pyridostigmine (Mestinon)
  • Prolongs half life of Ach in synaptic cleft
• Immunosupressive therapies:
  
  • corticosteroids suppress antibody synthesis
• Plasmaphoresis:
  
  1. Removal of whole blood from body
  2. Separation of cellular elements
  3. Reinfusion in saline or plasma substitute
  • Removes antibodies to Ach receptor
  • Relieves symptoms only temporarily

Question 18

Disorders of motor neurons:

• Lower Motor Neurons:
• Upper Motor Neurons:

Answer 18

• Lower motor neurons:
  
  • primary motor neurons in spinal cord, brainstem
  • directly innervate skeletal muscles
• Upper motor neurons:
  
  • neurons in higher regions of brain, brainstem, cortex that descend
  • synapse on lower motor neurons to control movement

Question 19

Disorders of Motor Neurons:

Clinical Symptoms

• Lower Motor Neurons:
• Upper Motor Neurons:

Answer 19

• Lower motor neuron disorders:
  
  • atrophy
  • fasciculations
    
    • involuntary contraction, twitching
  • decreased muscle tone
  • loss of tendon reflexes
  • weak, wasted and twitching muscles
• Upper motor neurons and axons:
  
  • spasticity
  • overactive tendon reflexes
  • abnormal plantar extension reflex
    
    • Babinski sign

Question 20

Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease):

Answer 20

• Progressive degeneration of both upper and lower motor neurons
• “Amyotrophic” = muscle atrophy
• “Lateral sclerosis” = hardness of spinal cord
  
  • Hardness results from proliferation of astrocytes
  • Scarring of lateral columns of spinal cord

Question 21

Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease):

Pathophysiology

Answer 21

• Disease of corticospinal tracts:
  
  • carry axons of premotor cells from cortex and brain stem to spinal cord
• Premotor neurons in cortex, brain stem and spinal cord also degenerate progressively
• Loss of motor neurons in ventral horn of spinal cord
• Loss of motor nuclei in lower brainstem
• Degeneration of corticospinal tracts
• Loss of Betz cells and large Pyramidal neurons
  in layer V of motor cortex
• Usually spares ocular muscles, voluntary control
  of bladder sphincters

Question 22

Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease):

Symptoms

Answer 22

Combined upper and lower motor neuron signs:

• Lower MN: Progressive weakness of arms or legs, atrophy, fasciculations (involuntary muscle contractions/twitching), cramps
• Upper MN: Spasticity, hyperreflexia, Babinski’s sign

Other signs:

• Dysarthria (slurred, slow, clumsy speech)
• Dysphagia (swallowing dysfunction)
• Respiratory muscle weakness and failure
• Head droop often present due to weakness of neck muscles
• Emotional incontinence:
  
  • ​due to lesions of corticobulbar pathways in brainstem
  • leads to abnormal reflex activation of laughter and crying circuits in brainstem
    
    • uncontrollable
    • explosive speech
  • without accompanying emotions:
    
    • pseudobulbar affect

Question 23

Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease):

• Cause:
• Treatment

Answer 23

• Causes: Not known
  
  • Most cases occur sporadically
  • Hypotheses: Accumulation of oxidative free radicals? Viral infections
  • Prognosis: 50% die within 3 yrs of onset; 90% die within 6 yrs of onset
• Treatment: No cure
  
  • Education and support from family/friends
  • Riluzole: blocks glutamate release prolongs survival by several months
  • Neurotrophic/growth factors
  • Antioxidants

Question 24

Disorders of peripheral nerves:
Neuropathy

Answer 24

• peripheral nerve disease
• Site of pathology may be in the axons, myelin or both
• Can affect large-diameter (Aβ fibers) or small-diameter fibers (C fibers).
• Usually affect both sensory and motor fibers in the nerve (often one is preferentially affected)
• Damage can be reversible or permanent.
• Location of defect can be focal (mononeuropathy) or generalized (polyneuropathy)

Question 25

What can cause neuropathies?

Answer 25

* Important causes of neuropathy: 1. **Diabetes** (microvascular blood supply to peripheral nerve is damaged) 2. **Mechanical trauma** (laceration, entrapment by bone) 3. **Infectious disease** (Lyme disease, HIV, CMV, varicella-zoster virus, hepatitis B) 4. toxins 5. malnutrition 6. **immune disorders (eg. Guillain-Barré syndrome)**

Question 26

How do polyneuropathies affect the peripheral nerve roots?

Answer 26

* **Distal symmetrical polyneuropathies** cause bilateral sensory loss in a **“glove and stocking”** distribution * in all modalities * Specific nerve or nerve root lesions cause **sensory loss in specific territories** * **Associated deficits of lesions** of the peripheral nerves or nerve roots **often include lower motor neuron-type weaknesses**

Question 27

**Guillain-Barré syndrome:**

Answer 27

* **Acute inflammatory demyelinating polyneuropathy** * Acute because it onset is rapid and patients **often have near full recovery** * Onset begins **1-2 weeks after viral infection**

Question 28

**Guillain-Barré syndrome:** **Pathophysiology**

Answer 28

* Inflammatory cells and antibodies: * attack the myelin sheath around peripheral nerves * myelin breaks down * axons are damaged * Conduction in motor nerves is slowed or blocked

Question 29

**Guillain-Barré syndrome:** **Symptoms**

Answer 29

* **Tingling of hands and feet** (crawling skin) * parethesia * Insensitivity to heat, cold * Difficulty getting out of chair * Rapid onset of weakness in legs and arms * Paralysis of legs & arms * Motor loss primary, can be sensory loss * Weakness and paralysis of breathing muscles, eyes and face * **Severe cases:** patient may become paralyzed and require ventilation. * **Loss of stretch reflex (Areflexia)** * May lack plantar reflexes completely due to motor weakness & peripheral denervation; otherwise, plantar reflex normal

Question 30

**Guillain-Barré syndrome:** **Cause**

Answer 30

Unknown

Question 31

**Guillain-Barré syndrome:** **Treatment**

Answer 31

* **Plasmaphoresis:** 1. Removal of whole blood from body 2. Separation of cellular elements 3. Reinfusion in saline or plasma substitute * **Immunoglobulin therapy (I.V.)** * Affects 1 in 100,000 * **Prognosis:** Most people recover within weeks to months * Length of illness is unpredictable * Majority of patients return to normal, near normal lifestyle