Motor dysfunction: motor unit & myopathic disease <ul><li>Learning objective </li></ul><ul><ul><li>To understand and describe </li></ul></ul><ul><ul><ul><li>Myopathic and neurogenic disorders </li></ul></ul></ul><ul><ul><ul><li>Four examples of motor dysfunction: Muscular dystrophy, Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis, Cerebral Palsy </li></ul></ul></ul>
Motor dysfunction Characteristic of the disease depends on the specific component of motor unit affected. Different clinical implications for different sources of disease. Myopathic: problems with the muscle Neurogenic: problems with the motor neuron and ‘pre’-motor neuron
Characteristics of the disease Nerve cell body: motor unit disease (1) Motor neuron axon/neuromuscular junction: peripheral neuropathy (2&3) Muscle degeneration: myopathy (4)
Neurogenic vs Myopathic diseases Criteria for distinguishing neurogenic (cell body & axon) versus myopathic (muscle) diseases. Myopathic: – main symptom: muscular weakness/wasting (atrophy) – leads to difficulty walking, lifting, etc. – also myotonia, myalgia, cramps Neurogenic diseases: – have these characteristics also, but also ... – tendon reflexes lost – gradual weakening – fasciculations (visible muscle twitches)
Upper and Lower motor neurons Each produces distinctive symptoms
Neurogenic vs Myopathic diseases Normal muscle Denervated muscle Myopathy Neurogenic and myopathic diseases have different effects on the motor unit.
Neurogenic vs Myopathic diseases Normal muscle Denervated muscle Myopathy EMG activity during rest, slight contraction, and maximum contraction – to distinguish between neurogenic and myopathic diseases.
Neurogenic vs Myopathic diseases Biopsy results show histochemistry differences in the muscle fibres: Type I and II fibres usually equal & distributed randomly Neuropathy: can see size changes, clustering Myopathy: can see damage
Neuropathies: symptom mechanisms Motor neuron disease: affects motor neurons leaving sensory neurons intact Peripheral neuropathies affect sensory and motor functions – often have paresthesias (numbness, tingling, etc) May be categorized as ‘demyelinating’ or ‘axonal’ – demyelinating more common
Demyelination Record action potentials after simulating the motor nerve at two distances to determine conduction velocity.
Demyelination Leads to slowing of conduction velocity In partially demyelinated nerve fibers, the action potentials propagate less efficiently.
Demyelination Nerves with different amounts of myelin (normal or partial) will conduct at different velocities, so lose synchrony of conduction. Can lead to reflex problems and odd sensations. insulation loss
Demyelination: Causes Viral: certain viruses can affect motor nerves selectively (e.g. poliomyelitus) Neonatal hypoxia (e.g. cerebral palsy) Genetic (e.g. muscular dystrophies) Unknown (e.g., multiple sclerosis)
Case 1: Duchenne Muscular Dystrophy Description: Genetic disorders characterized by progressive muscle wasting and weakness that begin with microscopic changes in the muscle. Shows signs of muscle weakness as early as age 3. The disease gradually weakens the skeletal or voluntary muscles, esp. those in the arms, legs and trunk. By the early teens, the heart and respiratory muscles may also be affected.
Case 1: Duchenne Muscular Dystrophy Symptoms (boys only) Children with the disorder are often late in learning to walk – clumsy, unsteady gait, difficulty raising arms, walk on toes – lose the ability to walk sometime between ages 7 & 12 – in teen years, activities involving the arms, legs or trunk require assistance or mechanical support
Case 1: Duchenne Muscular Dystrophy Muscle hypertrophy: enlarge muscles, esp the calf – increases with age – most commonly due to muscle fibrosis
Causes of Duchenne Muscular Dystrophy An absence of dystrophin, a protein that helps keep muscle cells intact. Dystrophin strengthens muscle cells by anchoring elements of the internal cytoskeleton to the surface membrane.
Causes of Duchenne Muscular Dystrophy Without it, the cell membrane becomes permeable, so that extracellular components enter the cell, increasing the internal pressure until the muscle cell "explodes" and dies.
Case 2: Amyotrophic Lateral Sclerosis Amyotrophic: neurogenic muscle atrophy, Lateral sclerosis: hardening of lateral corticospinal tracts Description: Upper and lower motor neuron disease Motor neurons undergo shrinkage, caused by altered cytoskeleton – they innervate less and less musculature, and those muscles atrophy Mean onset age: 56-63
Case 2: Amyotrophic Lateral Sclerosis Symptoms: Initially, muscle weakness and stiffness Usually the first muscles affected are those in the hands, arms and legs. (lateral CS tracts) Speech problems, such as slurring, hoarseness, or decreased volume may also occur (dysarthria)
Case 2: Amyotrophic Lateral Sclerosis Symptoms: Motor neuron signs (normal sensation): atrophy, hyperactive MSR, hyper/hypotonia, Babinski’s sign, spasticity, fasciculations. Eventually, the ability of the brain to start and control voluntary movement is lost.
Case 2: Amyotrophic Lateral Sclerosis Causes: Exact causes of the neural degeneration is unknown 5 to10 % can be attributed to heredity – there are multiple genes in which, if mutated, may cause ALS Suspects: viruses, neurotoxins , heavy metals, DNA defects (especially in familial ALS), immune system abnormalities, and enzyme abnormalities
Case 2: Amyotrophic Lateral Sclerosis Treatment: Motor deficits only. Sensory and cognitive function intact Treatment focuses on relieving symptoms and maintaining an optimal quality of life Medications for spasticity, discomfort, pain Physical therapy for cramping, contractures
Case 3: Multiple Sclerosis Description: Myelin is lost in multiple areas, leaving scar tissue called sclerosis. – damaged areas are also known as plaques or lesions – sometimes the nerve fiber itself is damaged or broken MS is a chronic, unpredictable neurological disease The majority of people with MS don’t become severely disabled.
Case 3: Multiple Sclerosis Symptoms: Wide range of unpredictable symptoms, vary from person to person, time to time – can affect vision, speech, balance, bladder function, coordination – may cause dizziness, pain, and tremors Age onset: peaks between 20 & 30 years Most people with MS are diagnosed between the ages of 20 and 50. – Women twice as likely to get it
Case 3: Multiple Sclerosis Causes It is believed that MS is an autoimmune disease – myelin is attacked. Unknown what triggers the improper autoimmune reaction Several factors are involved Genetics Gender Environmental Triggers, possibilities include viruses, trauma, and heavy metals
Case 3: Multiple Sclerosis Treatment: In the past, steriods have been used to reduce the duration and severity of attacks in some patients, or the symptoms such as spasticity. Some of the FDA-approved drug treatments include: Synthetic protein (Glatiramer Acetate or Copaxone) used to simulate myelin basic protein (acts as a decoy) Mitoxantrone suppress attack (e.g. from T-cells) on the myelin sheath.
Case 4: Cerebral Palsy Description (not a disease, actually) A non-progressive medical condition that affects control of the muscles, muscle tone Cerebral means anything in the head and palsy refers to anything wrong with control of the muscles or joints in the body
Case 4: Cerebral Palsy Different types Spastic (high tone), ~50% Ataxic (low tone) ~25% Athetoid (mixed tone) ~25% Movement symptoms depend on type – affects limbs, face, mouth, head Learning disabilities in 25-50% of CP children – slower rate of learning Seizures in about 50% of children
Case 4: Cerebral Palsy Causes Injury to the brain before, during, or shortly after birth. In many cases, not sure what caused the brain injury or what could have prevented the injury. - Neonatal/perinatal: insufficient oxygen (hypoxia) and/or insufficient blood (ischemia) is a major cause of damage to the newborn infant’s brain - Prenatal: maternal infection or accident, maternal medical condition such as high blood pressure or diabetes
Case 4: Cerebral Palsy Treatments Exercise and it’s favourable impact factors Cardio-pulmonary condition- ing, muscle strength building and coordination. Therapies Physical, recreational, speech, occupational Adapted objects, communication & mobility aids