Motor Unit Pathophysiology

Neuro Course 4th Year

Neuro Course

General Principles of Motor Activity Voluntary movements Reflex movements Rhythmic motor patterns • Cortical • Brain stem and associated structures Brain Stem Centers Cerebellum Basal Ganglia • Spinal cord Final Common Pathway - lower motor neuron

Origin of Motor Unit Disease

Motor unit diseases can be broadly classified into four major categories: Spinal dystrophies (motor neuron body) Peripheral neuropathies (nerve: body+axon) Diseases of the myoneural junction Myopathies

Motor Deficits- Correlation of Signs with Anatomical LevelMUSCLE DISEASE: NEUROMUSCULAR JUNCTION:

PERIPHERAL NERVE:

Major Categories of Peripheral Nerve Disease1) Traumatic

2) Toxic/Metabolica) Systemic disorders (diabetes mellitus, uremia, liver disease)b) Nutritional (beriberi, pellagra, alcohol, vitamin E deficiency)c) Toxic-industrial (lead), drugsd) Endocrine (DM, hypothyroidism)

3) Inflammatory Neuropathiesa) Acute inflammtory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome)c) Infections: leprosy, diphtheria, lyme disease, rabies, HIV, infectious mononucleosis

4) Hereditary Neuropathiesa) Hereditary Motor and Sensory Neuropathies (HMSNs)b) Hereditary Sensory and Autonomic Neuropathiesc) Friedreich's ataxiad) Neurofibromatosis

Neuromuscular disordersMyasthenia gravis

Eaton-Lambert myasthenic syndrome

Muscle disordersInherited muscle diseases Congenital myopathies

Lack of structural proteins e.g. Merosin deficient Ultrastructural appearance

Central Core Lack of structural proteins

Dystrophinopathies (Becker, Duchenne) Sarcoglycanopathies

Alteration in muscle enzymes Calpain 3 Myotonic dystrophy

Defects in muscle energy metabolism– glyco(geno)lysis e.g. McArdles– lipid oxidation– mitochondrial defects

Acquired muscle diseases Drugs (steroids) Endocrine (DM, thyroid) Infectious (viral myositis, dermatomyositis) Intoxication (venom) Paraneoplastic Rhabdomyolysis

Muscle disordersMyopathya) static congenital myopathiesb) progressive genetically-determined wasting diseases or dystrophiesc) inflammatory myopathiesd) metabolic disorders

Neuropathy

Signs:a) atrophy/hypertrophyb) increased connective tissue, central nuclei, variation in fiber size, disturbances in architecturec) necrosis and regeneration

Muscle disorders – clinical signs

• Muscle pain

• Muscle weakness (limb, bulbar, respiratory)

• Muscle stiffness (myotonia)

• Breathlessness (respiratory or cardiovascular)

• Palpitations (cardiomyopathy or arrhythymia)

• Skin rash and other systemic features

• Myoglobinuria

Muscular Dystrophies1) Duchenne and Becker Muscular Dystrophy

2) Congenital Muscular Dystrophy

3) Myotonic Dystrophy(chloride transport abnormality)

Metabolic Myopathies

1) Disorders of Glycogen Metabolism

2) Mitochondrial Encephalomyopathies