Neurophysiological Basis of Movement

1. Neurophysiological Basis of Movement World VI: Motor Disorders

2. Site Disorder Neuron cell body ALS (Lou Gehrig’s disease) Root Cervical or lumbar radiculopathy Axon Axonal neuropathy Demyelination Guillain-Barré syndrome Neuromuscular synapse Myasthenia gravis Muscle Muscular dystrophy Lecture 30: Peripheral Muscular and Neurological Disorders Sites of Damage in Nerve and Muscle

3. Muscular Dystrophies • Genetic diseases: progressive weakness and degeneration of skeletal muscles • Duchenne and Becker dystrophy—1 in 3,500 to 5,000 births • Mostly males are affected

4. Muscular Dystrophies: Duchenne Dystrophy • Mutation of a gene responsible for dystrophin, a protein involved in maintaining integrity of muscle fibers • Clinical symptoms at 2 to 6 years; all muscles are affected • Late to walk; waddling, unsteady gait • Respirator dependence by the age of 20

5. Muscular Dystrophies: BeckerDystrophy • Similar to Duchenne dystrophy; mutation of a gene responsible for dystrophin • Clinical symptoms appear at adolescence • Slower disease progression; longer life expectancy

6. Muscular Dystrophies: MyotonicDystrophy • Most common adult form of muscular dystrophy • Myotonia: prolonged episode of muscle activity after its voluntary contraction • Commonly in finger and facial muscles • High-stepping, floppy-footed gait • Long face; drooping eyelids

7. Myotonic Discharge

8. Stiff Person Syndrome • Excessive motoneuron excitation • Starts at 30 to 60 years of age • Leads to boardlike rigidity of trunk muscles

9. Stiff Person Syndrome

10. Continuous Muscle Fiber Activity Syndromes Tetanus (induced by tetanus toxin): • The toxin blocks postsynaptic inhibition at the spinal level. • EMG bursts can be stopped by neuromuscular or peripheral nerve block. • Discharges are attenuated during sleep and under general or spinal anesthesia.

11. Stiff person syndrome: • Excessive motoneuron excitation • Coactivation of agonist–antagonist muscles • Proximal muscles are particularly involved Neuromyotonia: • Continuous activity of single muscle fibers • Seen at rest and on the background of vol. activation • Defect probably in the motor axon terminals Continuous Muscle Fiber Activity Syndromes

12. Neuromyotonia Small potentials on the background on voluntary activation

13. Disorder of transmission at the neuromuscular synapse • Clinical signs: • fatigue, exhaustion, muscle atrophy • any muscle(s) can be affected, but especially eye, face, lip, tongue, throat, neck, and limb muscles • ocular signs (eyelid droop; inability to open one eye) • facial weakness (stiffness of the face; difficulties with chewing, swallowing, laughing, and speech [dysarthria]) • may lead to ventilatory insufficiency and death Myasthenia Gravis

14. Myasthenia Gravis: Epidemiology • 3 to 4 new cases per million annually • Prevalence: 60 cases per million • Can start at any age • Women are affected 2:1 over men • Death rate in the 1930s was 40%; death rate in the 1970s–1980s was 7%

15. Myasthenia Gravis: Physiology • Autoimmune process (the body produced antibodies to ACh receptors) • Reduction of ACh receptors • Reduction of postsynaptic potentials

16. Myasthenia Gravis: Increased Duration of Action Potentials in the Muscle

17. Myasthenia Gravis: Treatment • ACh-esterase inhibitors (neostigmine, distigmine) • Thymectomy to suppress autoimmune processes • Plasmapheresis to remove autoimmune antibodies • Side effects with any treatment

18. Peripheral Neuropathies: Mononeuropathies • Slowed conduction in a single nerve • Reduced amplitude of motor and/or sensory potentials • Signs of denervation • Carpal tunnel syndrome: entrapment of the median nerve at the wrist • Ulnar nerve can be entrapped near the elbow • Brachial plexus lesions: mostly seen in muscles innervated by median and ulnar nerves • Peroneal: peroneal pressure palsy • Tibial: tarsal tunnel syndrome • Sciatic

19. Carpal Tunnel Syndrome

20. Peripheral Neuropathies: Multiple Mononeuropathies • Diabetes mellitus • Polyarteritis nodosa (connective tissue disorder, vasculitis) • Leprosy

21. Diabetes (Diabetes Mellitus): Impaired Ability to Metabolize Glucose • Total number of cases in the U.S.: 16 million • Yearly increase: 650,000 new cases • Long-term complications: • Peripheral sensory neuropathy • Peripheral motor neuropathy • Loss of autonomic nerve function • Atrophy of peripheral tissues

22. Clinically apparent peripheral nerve damage occurs: • In 25% of patients after 10 years • In 50% of patients after 20 years Consequences: • Loss of balance and coordination • Increased probability of falls, fractures, bruises, etc. Diabetes

23. Effects of muscle vibration on posture: • Lower during vibration of Achilles tendon • Higher during vibration of hamstrings Diabetes Reorganization of postural control: switch to alternative sources of information

24. Consequence of Diabetes: Atrophy of Peripheral Tissues • Is it a consequence of inadequate blood supply? • Is it a consequence of abnormal pressure distribution with foci of high pressure? • Studies by the group of Peter Cavanagh

25. VIF VIF VIF VIF Diabetes

26. Peripheral Neuropathies: Polyneuropathies • May be associated with demyelinating neuropathies • Guillain-Barré syndrome: reduced recruitment; conduction block; may result in permanent axonal loss • Chronic inflammatory demyelinating polyneuropathy: common recovery, but nerve conduction velocity may remain slow

27. Peripheral Neuropathies: Polyneuropathies • Axonal neuropathies (mostly of toxic origin) • Neuronal degenerations: • Amyotrophic lateral sclerosis (Lou Gehrig’s disease) • Poliomyelitis (enterovirus destroying anterior horn cells; EMGs show chronic denervation; may lead to weakness and pain—a postpolyo syndrome)

28. ALS • 20,000 Americans have ALS (one in 15,000). • 5,000 people in the United States are diagnosed with ALS each year. • Men are affected more often than women. • ALS most commonly strikes people between 40 and 60 years of age. • About 5 to 10 percent of all ALS cases are inherited. • About 20 percent of all familial cases result from a specific genetic defect: mutation of superoxide dismutase 1 (SOD1).

29. ALS • The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; slurred and nasal speech; or difficulty chewing or swallowing. • Patients have increasing problems with moving, swallowing (dysphagia), and speaking or forming words (dysarthria). • Patients have tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia).