Neurophysiological Basis of Movement World VI: Motor Disorders

Sites of Damage in Nerve and Muscle SiteDisorder Neuron cell bodyALS (Lou Gehrig’s disease) RootCervical or lumbar radiculopathy AxonAxonal neuropathy DemyelinationGuillain-Barré syndrome Neuromuscular synapseMyasthenia gravis MuscleMuscular dystrophy Lecture 30: Peripheral Muscular and 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 Fiber Activity 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 Fiber Activity 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 Duration of 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 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