Peripheral Nervous System Disorders General Pathophysiology 3rd year

Functional Composition of the PNS

Developmental Abnormalities 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

Degenerative Changes Axonal injury Anterograde degeneration (Wallerian degeneration) Retrograde Degeneration

Changes during Nerve Degeneration

Diseases of Myelin DEMYELINATING DISEASES DYSMYELINATING DISEASES PERIPHERAL NERVE DEMYELINATION Guillain-Barré syndrome: autoimmune, potential for remyelination with complete recovery

Neurodegenerative diseases ALS - Amyotrophic lateral sclerosis (Lou Gehrig’s disease) Lower plus upper motor neurons lesion Poliomyelitis anterior acuta: Lower motor neurons are destroyed.

Hereditary motor and sensory neuropathies (HMSN) 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)

Acquired Neuropathies Diabetic Neuropathy Alcoholic polyneuropathy Entrapment/Compression Neuropathies AIDS neuropathy

Clinical Patterns of Neuropathy motor changes: sensory loss: autonomic changes (frequently accompany polyneuropathies): skeletal and joint changes:

Disorders of the Neuro-Muscular Junction Myasthenia gravis Lambert-Eaton Syndrome: Botulinum toxin Aminoglycosides and excess Magnesium Black widow spider venom Cobratoxins

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

Acquired Inflammatory Muscle Diseases Polymyositis Dermatomyositis

Acquired Metabolic/Endocrine Muscle Diseases Hyperthyroidism Hypothyroidism Cushing's Syndrome and steroid induced myopathy. Acromegaly Osteomalacia Hyperparathyoidism Drugs and Toxins

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

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

Neuropathies vs. Myopathies 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. 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.

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

Peripheral Autonomic Disorders Pure Autonomic Failure Autonomic Neuropathy

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 immune-mediated 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 walking stairs, combing hair) with no sensory deficits Diffuse muscle dysfunction, as occurs in diffuse 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)