Neurophysiological Basis of Movement

World VI:Motor Disorders

Sites of Damage in Nerve and Muscle

Site Disorder

Neuron cell body ALS (Lou Gehrig’s disease)Root Cervical or lumbar radiculopathyAxon Axonal neuropathyDemyelination Guillain-Barré syndromeNeuromuscular synapse Myasthenia gravisMuscle Muscular dystrophy

Lecture 30: Peripheral Muscularand Neurological Disorders

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

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

Muscular Dystrophies:Duchenne Dystrophy

Similar to Duchenne dystrophy; mutation of a gene responsible for dystrophin

Clinical symptoms appear at adolescence

Slower disease progression; longer life expectancy

Muscular Dystrophies:Becker Dystrophy

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

Muscular Dystrophies:Myotonic Dystrophy

Myotonic Discharge

Stiff Person Syndrome

Excessive motoneuron excitation

Starts at 30 to 60 years of age

Leads to boardlike rigidity of trunk muscles

Stiff Person Syndrome

Continuous Muscle FiberActivity Syndromes

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.

Tetanus (induced by tetanus toxin):

Excessive motoneuron excitation Coactivation of agonist–antagonist muscles Proximal muscles are particularly involved

Stiff person syndrome:

Continuous activity of single muscle fibers Seen at rest and on the background of vol. activation Defect probably in the motor axon terminals

Neuromyotonia:

Continuous Muscle FiberActivity Syndromes

Neuromyotonia

Small potentials on the background on voluntary activation

Myasthenia Gravis

– 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

Disorder of transmission at the neuromuscular synapse

Clinical signs:

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%

Myasthenia Gravis: Epidemiology

Autoimmune process (the body produced antibodies to ACh receptors)

Reduction of ACh receptors

Reduction of postsynaptic potentials

Myasthenia Gravis: Physiology

Myasthenia Gravis: Increased Durationof Action Potentials in the Muscle

ACh-esterase inhibitors (neostigmine, distigmine)

Thymectomy to suppress autoimmune processes

Plasmapheresis to remove autoimmune antibodies

Side effects with any treatment

Myasthenia Gravis: Treatment

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

Carpal Tunnel Syndrome

Diabetes mellitus

Polyarteritis nodosa (connective tissue disorder, vasculitis)

Leprosy

Peripheral Neuropathies:Multiple Mononeuropathies

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

Diabetes

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.

Lower during vibration of Achilles tendon

Higher during vibration of hamstrings

Effects of muscle vibration on posture:

Reorganization of postural control: switch to alternative sources of information

Diabetes

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

VIF

VIF

VIF

VIF

Diabetes

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

Peripheral Neuropathies:Polyneuropathies

– 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)

Axonal neuropathies (mostly of toxic origin)

Neuronal degenerations:

Peripheral Neuropathies:Polyneuropathies

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).

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).

ALS