1. Peripheral Nervous System Disorders
General Pathophysiology 3rd year

2. Functional Composition of the PNS

3. 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

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

5. Changes during Nerve Degeneration

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

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

8. 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)

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

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

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

12. 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

13. Acquired Inflammatory Muscle Diseases
Polymyositis Dermatomyositis

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

15. 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

16. 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

17. 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.

18. 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

19. Peripheral Autonomic Disorders
Pure Autonomic Failure Autonomic Neuropathy

20. 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)