Transcript Peripheral Nervous System Disorders

Peripheral Nervous System Disorders
General Pathophysiology 3rd year
Functional Composition of the PNS
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Developmental Abnormalities
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Organ induction (2.5-6 weeks): neural tube defects
Neuronal (glial) migration (3-6 months)
Neuronal Storage Disease
Myelination (2 months-juvenile)
Synaptogenesis (20 week gestation-adulthood)
In general, earlier insults cause more severe structural damage
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Degenerative Changes
Axonal injury
– Anterograde degeneration (Wallerian degeneration)
– Retrograde Degeneration
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Changes during Nerve Degeneration
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Diseases of Myelin
DEMYELINATING DISEASES
DYSMYELINATING DISEASES
PERIPHERAL NERVE DEMYELINATION
Guillain-Barré syndrome: autoimmune, potential for
remyelination with complete recovery
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Neurodegenerative diseases
ALS - Amyotrophic lateral sclerosis (Lou Gehrig’s disease)
Lower plus upper motor neurons lesion
Poliomyelitis anterior acuta: Lower motor neurons are
destroyed.
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Hereditary motor and sensory neuropathies (HMSN)
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Hypertrophic Charcot-Marie-Tooth Disease (HMSN Type I)
Neuronal Charcot-Marie-Tooth Disease (HMSN Type II)
Dejerine-Sottas Disease (HMSN Type III)
Refsum's Disease (HMSN Type IV)
Friedrich's Ataxia (HMSN Type V)
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Acquired Neuropathies
• Diabetic Neuropathy
• Alcoholic polyneuropathy
• Entrapment/Compression Neuropathies
• AIDS neuropathy
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Clinical Patterns of Neuropathy
motor changes:
sensory loss:
autonomic changes (frequently accompany
polyneuropathies):
skeletal and joint changes:
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Disorders of the Neuro-Muscular Junction
• Myasthenia gravis
• Lambert-Eaton Syndrome:
• Botulinum toxin
• Aminoglycosides and excess Magnesium
• Black widow spider venom
• Cobratoxins
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Muscle diseases -Myopathies
There are three major groups of muscle diseases:
1) Acquired inflammatory
2) Acquired metabolic/endocrine
3) Inherited: dystrophies and enzyme defects of glycogen and
lipid utilisation.
The term myopathy is commonly used to designate an abnormal
condition, disorder, or disease involving skeletal muscle.
Myopathies range from muscular dystrophies, metabolic
myopathies to myotonic disorders .
• Muscular Dystrophies
• Metabolic Myopathies
• Myotonic Disorders
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Acquired Inflammatory Muscle Diseases
Polymyositis
Dermatomyositis
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Acquired Metabolic/Endocrine Muscle Diseases
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Hyperthyroidism
Hypothyroidism
Cushing's Syndrome and steroid induced myopathy.
Acromegaly
Osteomalacia
Hyperparathyoidism
Drugs and Toxins
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Inherited Muscle Diseases
Muscle Dystrophy.
• These are usually disorders of slow onset with weakness and
muscle wasting in specific patterns.
• The disorders will be classified here according to pattern of
inheritance.
X-Linked
Duchenne's Muscular Dystrophy.
Becker's Muscular Dystrophy.
Autosomal Dominant
Autosomal Recessive
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Disorders of membrane excitability
Myotonic Dystrophy.
Myotonia Congenita.
Sodium channel abnormalities :
• Hyperkalemic periodic paralysis
• Paramyotonia congenita
• Myotonia
Chloride channel abnormalities:
Abnormalities in voltage-activated calcium channels:
• Hypokalemic periodic paralysis
Mutations in the ryanodine receptor channel
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Neuropathies vs. Myopathies
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Neuropathies
– Loss of axons so ↓ number of motor units
– Nerves reinnervate muscle fibers to make abnormally large motor units with
contractions of longer duration
– ↓ number of motor units recruited during contraction; the few motor units that are
recruited may be larger in size, longer in duration, and polyphasic in appearance.
– Nerve conduction velocity is slowed either a small amount (if axonal injury, Wallerian
degeneration) or a large amount (if demyelinating diease). Potential amplitudes are also
reduced in the same manner.
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Myopathies
– Motor units have less number of muscle fibers→ normal number of units, ↓ electrical
activity, shorter in duration
– Nerve conduction velocity is normal. ↓ potential amplitude.
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Autonomic Disorders
• The autonomic nervous system controls blood pressure, heart
rate, body temperature, sexual function, and the motility of
the intestine and the urinary bladder.
Signs and symptoms of autonomic dysfunction include:
• Orthostatic hypotension (a fall in blood pressure upon
standing)
• Abnormal gastrointestinal motility (constipation or diarrhea)
• Bladder dysfunction (urinary incontinence or retention)
• Erectile difficulties (impotence)
• Abnormalities in sweating (excessive sweating or lack of
sweating)
• Abnormal temperature control
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Peripheral Autonomic Disorders
Pure Autonomic Failure
Autonomic Neuropathy
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Clinical Clues to Causes of Peripheral Nervous System Disorders
Finding
Cause to Consider
Symmetric, diffuse deficits
Diffuse disorders (eg, toxic-metabolic, hereditary,
infectious, or inflammatory disorders; most immunemediated disorders)
Unilateral deficits
Focal disorders (eg, mononeuropathies, plexopathies)
Deficits localized to one or more peripheral nervous system
structures (eg, nerve root, spinal nerve, nerve plexus, single
peripheral nerve, multiple mononeuropathy)
Lesion in a peripheral nervous system structure
Stocking-glove distribution of deficits
Diffuse peripheral polyneuropathies, possibly axonal
Disproportionate weakness of proximal muscles (eg, difficulty Diffuse muscle dysfunction, as occurs in diffuse
walking stairs, combing hair) with no sensory deficits
myopathies
Possibly disorders of the neuromuscular junction if
the eyes are affected
Chronic, progressive weakness affecting mostly distal
muscles with no sensory deficits
Motor neuron disorders
Buzzing and tingling with motor weakness and decreased
reflexes
Demyelination
Profound motor weakness with minimal atrophy
Acquired demyelinating polyneuropathy
Deficient pain and temperature sensation; weakness
proportional to atrophy; disproportionately mild reflex
abnormalities, usually more distal than proximal
Vascular disorders (eg, vasculitis, ischemia)
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