1. Peripheral Neuropathy
Rebecca Meyerson, MD
Neurology
SMDC

2. Peripheral Nervous System
Motor peripheral nerves: neuron in the anterior horn of the spinal cord, axon extends peripherally to the skin
Sensory peripheral nerves: neuron in the dorsal root ganglia, axon extending peripherally to the skin surface
Pathology of the peripheral nerve may take place at any place along its pathway, and any peripheral nerve lesion must first be localized.
Anterior horn cell
Spinal nerve root
Nerve plexus
Nerve (certain places are prone to compression or injury)
Neuromuscular junction
Muscle

3. Differentiating upper motor neuron and lower motor neuron lesions
UMN lesion
LMN lesion
Muscle bulk
Preserved
Atrophy
Muscle tone
Spastic
Flaccid
Spontaneous movements
None
Fasciculation's
Reflexes
Increased
Absent
Babinski reflex
Present

4. Peripheral Nerves Contain:
Motor nerve fibers
Sensory nerve fibers
Large myelinated fibers: vibration, proprioception, light touch
Small unmyelinated fibers: pain and temperature
Autonomic nerve fibers

6. Nerve injury Compressive injury Vascular insult Axonal damage
Metabolic disruption of axonal transport
Ion channel dysfunction
Demyelination
Infiltrative process

8. Differentiating Clinical Features
Radiculopathy
Radiating pain in a nerve root distribution
Weakness
Decreased DTR
Decreased sensation
Often associated with back and neck pain, and muscle stiffness
Aggravated by sneeze, cough, valsalva maneuver, neck/trunk movement
Plexopathy
Does not fit nicely into a root or nerve pattern
Is typically unilateral
Mononeuropathy
Single nerve involved
Mononeuropathy multiplex
Multiple single nerves involved
Polyneuropathy
Chronic and insidious onset
Length dependent pattern

9. Cervical Radiculopathies

12. Lumbar Radiculopathies
L5 and S1 nerve root compression most common
Pain radiates in the distribution of the nerve root

14. Mononeuropathies of the upper extremities
Median neuropathy
Ulnar neuropathy
Radial neuropathy

15. Median neuropathy Vulnerable at the carpal tunnel
Most common, most common neuro prob in pregnancy
Pain severe at night
Pain thumb, index and middle finger, split sensory loss 4th digit
Motor usually confined to abductor pollicis brevis

20. Ulnar neuropathy Injury usually occurs at the elbow
May occur from repeated and trivial trauma (resting elbow)
Tardy ulnar palsy occurs after a childhood fracture of the supracondylar humerus
Sensory loss medial aspect hand and forearm, medial 2 fingers
Weakness of intrinsic hand muscles

22. Radial neuropathy

23. Radial neuropathy
Damaged in the axilla by incorrect use of a crutch, causing weakness of all the radial nerve innervated muscles – triceps, wrist extensors, finger extensors and brachoradialis.
Classic appearance – wrist drop and finger extension weakness. Sensory loss occurs on the dorsum of the hand
Injury of the radial nerve in the medial aspect of the arm results in the Saturday night palsy. Occurs when inebriated or heavily sedated patients go to sleep with their arm hanging over the back of a chair or over the edge of the bed.

26. Peroneal neuropathy
Nerve in leg most often damaged, usually by compression at the fibular neck where protected only by skin and fascia
Weakness of dorsiflexion (foot drop) and eversion of the foot. (Distinction between peroneal and L5 root lesion – L5 affects dorsiflexion and inversion)
Sensory loss occurs in the lower anterolateral leg and on to the dorsum of the foot in a triangular area.

28. Assessment of UE strength

29. Assessment of UE Strength

30. UE Radiculopathies

31. Sensory deficit in UE Mononeuropathies

32. Assessment of LE Strength

33. LE Radiculopathies

34. Electrodiagnostic studies

35. Electrodiagnostic studies

36. Clinical features of polyneuropathies
Motor symptoms – weak, atrophy, diminished reflexes
Sensory symptoms –
loss of small fiber (pain temperature), loss of large fiber (vibration, propriception, light touch)
Gain of abnormal sensation: allodynia, hyperalgesia, paresthesias
Autonomic symptoms – orthostatic hypotension, impotence, gastroparesis, altered sweating response
Orthopedic abnormalities – high arched feet and hammer toes suggests a long standing condition

37. Neurological clinical evaluation of polyneuropathy
Sensory: evaluate at least one test of both large and small fiber modalities ie: vibration and pain
Motor: assess muscle tone, visual inspection for fasciculations and atrophy, in addition to muscle srength
Reflexes
Gait: inability to walk on heels early sign of distal weakness
Romberg: evaluates distal large fiber sensation

38. Clinical evaluation cont
Electrodiagnostic studies (NCS/EMG)
Extablish extent and involvement of nerve pathology
Distinguish primary axonal or demyelinating process
Will not tell you anything about small fiber dysfunction
Nerve biopsy

39. Causes of polyneuropathy
Diabetes, alcohol, hypothyroidism, uremia, amyloidosis, medications, B 12 deficiency, B1 deficiency, B6 deficiency or toxicity, arsenic, lead, HIV, hepatitis, leprosy, lyme, polyarteritis nodosum, lupus, sjogrens, chronic inflammatory demyelinating polyneuropathy, guillian barre syndrome, paraneoplastic, charcot marie tooth, diptheria, thallium, porphyoria, acrylamide, gold salts, methotrexae, nitrofurantoin………………………

40. Schema to tease out etiology of polyneuropathies
Timing: chronic vs acute
Modalities affected (large fiber, small fiber, motor, sensory)
Distribution (symmetric, asymmetric, focal, multiple focal nerves)
Nature of primary pathology (axonal vs demyelinating

41. Metabolic causes of polyneuropathy
Diabetes: most common cause of neuropathy
Occurs from a combination of metabolic and vascular abnormalities due to hyperglycemia
Severity of diabetic neuropathy correlates with the severity of hyperlipidemia and hypertension
No treatment to reverse pathology
Management: optimize blood glucose control, foot care, and symptomatic treatment of neuropathic pain

42. Metabolic etiologies Diabetes:
typically cause symmetric sensorimotor axonal neuropathy
Other presentations:
sensorimotor demyelination
prominent autonomic involvement
mononeuropathy-especially carpal tunnel syndrome, truncal radiculopathies, cranial neuropathies (CN3)
Mononeuropathy multiplex: results in simultaneous dysfunction of several peripheral nerves, due to ischemic infarction of the vasa nervorum
Diabetic amyotrophy (ischemic infarction of the lumbosacral plexus)
Uremia: symmetric sensorimotor axonal neuropathy
Hypothyroidism: sensorimotor neuropathy, entrapment neuropathy (carpal tunnel syndrome)

43. Nutritional etiologies of polyneuropathies
B12 deficiency: sensorimotor axonopathy, myelopathy involving the posterior columns
B6 deficiency or toxicity: myelopathy and axonal sensorimotor neuropathy
Thiamine deficiency: (wernickes-korsakoff syndrome), axonal sensorimotor neuropathy, can be rapid onset and progression. (thiamine needed for metabolism carbohydrates/amino acids)
Copper deficiency: axonal sensorimotor axonopathy, myelopathy
Zinc toxicity: due to induced copper deficiency, axonal sensorimotor neuopathy, myelopathy with posterior column (sensory ataxia)
Vitamin E deficiency: axonal sensorimotor neuropathy, myelopathy

44. Infectious etiologies of polyneuropathies
HIV
Distal symmetric sensori>motor neuropathy
Inflammatory polyneuritis of buillian barre type at the time of seroconversion
Lyme disease
Multifocal spinal root or cranial nerve (often facial nerve palsy)
Demyelinating and axonal neuropathy often with multiple nerve root involvement
Hepatitis C and cryoglobulinemia:
vasculitis associated
Painful, asymmetric sensorimotor polyneuropathy or multiple mononeuropathies
Diptheria:
Toxin mediated sensorimotor neuropathy
Prominent autonomic disurbance

45. Toxic etiologies of polyneuropathies
Alcohol: slowly progressive, distal, painful, symmetric sensorimotor axonal neuropathy. Nutritional factors likely contribute
Lead toxicity: motor predominant, often presents with radial nerve associated wrist drop
Arsenic toxicity: motor predominant sensorimotor demyelinating>axonal neuropathy. Can mimic guillian barre
Multiple medications: nitrofurantoin, vincristine, amiodarone, phenytoin: usually produce a sensorimotor axonal neuropathy

46. Inflammatory/immune mediated etiologies of polyneuropathy
Vasculitis: systemic lupus erythematosis, sjogrens, polyarterosis nodosum, wegeners granulomatosis, microscopic polyangiitis, rheumatoid arthritis
Painful mononeuropathies or mononeuropathy multiplex
Acute or subacute onset
Paraprotinemic neuropathy:
Monoclonal gammaopathy, excessive amounts of abnormal immunoglobulin produced by a single clone of plasma cell
Several distinct peripheral neuropathy syndromes
Symmetric polyneuropathy, (mononeuritis multiplex, mononeuropathy), demyelinating>axonal

47. Inflammatory/immune mediated etiologies of polyneuropathy
CIDP (chronic inflammatory demyelinating polyradiculoneuropathy)
Acquired neuropathy due to immune mediated demyelination
Chronic progressive or relapsing-remitting neuropathy
Symmetric sensorimotor neuropathy with predominant motor symptoms, demyelinating changes on EMG
Subacute weakness proximally and distally variable sensory loss, areflexia
Left untreated: continuously progressive or relapsing remitting course
Treatment: corticoids, IVIG, plasma exchange

48. Hereditary etiologies of polyneuropathy
Hereditary sensory motor neuropathy (HSMN) = charcot marie tooth (many genetic disorders identified, with distinct clinical syndromes)
Genetic defect of axonal and myelin proteins
Onset of symptoms is insidious and progression is indolent, often onset in childhood/adolenscence or early adulthood, progresses gradually throughout adult life
Significant motor involvement, striking atrophy of the muscles of the foot, calf and hands
Hereditary Sensory Motor Neuropathy HSMN-1
Demyelinating polyneuropathy
Autosomal dominant pattern
Striking atrophy calves (stork legs)
Large fiber sensory loss with marked reduction in vibratory perception and proprioception

50. Distal symmetric polyneuropathy
Pattern seen with most metabolic, toxic and nutritional etiologies
Axonal predominant
Length dependent (symptoms begin in the feet and progress rostrally), the stocking-glove pattern.
The offending agent affects protein synthesis in the cell body of the peripheral nerve and then impairs axonal transport
Dysfunction first occurs in the distal portions of the longest axons, thus in the most distal portions of the extremities
Small diameter axons are most susceptible to metabolic injury because of their small size and lack of reserve
Initial symptoms typically include autonomic dysfunction and small fiber sensory modalities, including loss of pain and temperature
Clinical presentation: numbness, paresthesias, burning discomfort
Loss sensation distal LE, later loss of achilles reflex and weakness intrinsic foot muscles

51. Distal symmetric polyneuropathy
Examples
Diabetes
Alcohol
Nutritional deficiencies
Medications

52. Symmetric or asymmetric demyelinating polyneuropathy
Demyelinating more than axonal involvement
Numbness and weakness in a length dependent fashion
Clinically: sensory loss in feet, and weakness (footdrop)
Examples:
Hereditary sensory motor neuropathies
CIDP

53. Multifocal axonal neuropathy (mononeuropathy multiplex)
Individual nerves are affected in a patchy fashion (ie: left median nruopathy, then right peroneal neuropathy)
Underlying pathology ischemic infarction of the vasa nervorum
Painful and cause profound weakness
Prognosis for recovery is good assuming the underlying disease can be suppressed
Examples:
Vasculitis
Diabetes

54. Acute polyneuropathies
Guillian Barre syndrome (acute inflammatory demyelinating polyradiculoneuropathy):
Rapidly progressive
Motor predominence
Diffuse polyradiculoneuropathy
Clinical presentation:
Nearly symmetric, rapidly ascending motor weakness often with associated paresthesias
Often striking autonomic involvement (resting tachycardia, fluctuations in blood pressure)

55. Guillian-Barre syndrome cont
Often follows a systemic infection
Campylobacor jejuni infection
Weakness reaches its nadir within the first 2 weeks, may require intubation and respiratory suppport
Rate of recovery is accelerated by plasma exchange or IVIG

57. Other acute neuropathies
Neurotoxins:
Medications – acute onset symmetric neuropathy
Toxic exposures – heavy metals
Vasculitic neuropathies – especially if multiorgan involvement, multifocality, or severe pain

58. Acute motor weakness
Disorders of neuromuscular transmission and muscle should be considered if rapidly progressing weakness without sensory findings

59. General principles of treatment of neuropathies
Patient education and counseling, genetic counseling
Withdrawal of medications suspected, or toxic exposure
Correction of nutritional and vitamin deficiencies
Treatment of alcoholism
Blood glucose control in diabetics
Specific drug therapies: chelating agents in lead neuropathy, prednisone in CIDP, plasmapheresis or IVIG for GBS
Pain control: gabapentin, carbamazepine, other anticonvulsants, tricyclics, transcutaneous electrical nerve stimulation
Meticulous foot care
Orthotic devices and splints
Surgical correction of entrapment neuropathies
Physical and occupational therapy