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 Level MUSCLE DISEASE: NEUROMUSCULAR JUNCTION: PERIPHERAL NERVE:

Major Categories of Peripheral Nerve Disease 1) Traumatic 2) Toxic/Metabolic a) Systemic disorders (diabetes mellitus, uremia, liver disease) b) Nutritional (beriberi, pellagra, alcohol, vitamin E deficiency) c) Toxic-industrial (lead), drugs d) Endocrine (DM, hypothyroidism) 3) Inflammatory Neuropathies a) Acute inflammtory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) c) Infections: leprosy, diphtheria, lyme disease, rabies, HIV, infectious mononucleosis 4) Hereditary Neuropathies a) Hereditary Motor and Sensory Neuropathies (HMSNs) b) Hereditary Sensory and Autonomic Neuropathies c) Friedreich's ataxia d) Neurofibromatosis

Neuromuscular disorders Myasthenia gravis Eaton-Lambert myasthenic syndrome

Muscle disorders Inherited 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 disorders Myopathy a) static congenital myopathies b) progressive genetically-determined wasting diseases or dystrophies c) inflammatory myopathies d) metabolic disorders Neuropathy Signs: a) atrophy/hypertrophy b) increased connective tissue, central nuclei, variation in fiber size, disturbances in architecture c) 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 Dystrophies 1) 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