Helpful to medical students

1. Peripheral Neuropathy

2. Introduction
• Peripheral neuropathy describes damage
to the peripheral nervous system.
• More than 100 types of peripheral
neuropathy have been identified, each
with its own characteristic set of
symptoms, pattern of development, and
prognosis.

3. • Impaired function and symptoms depend
on the type of nerves
– motor, sensory, or autonomic
• that are damaged.
Introduction

4. • Motor nerves
– control movements of all muscles under conscious
control, such as those used for walking, grasping
things, or talking.
• Sensory nerves
– transmit information about sensory experiences, such
as the feeling of a light touch or the pain resulting
from a cut.
• Autonomic nerves
– regulate biological activities that people do not control
consciously, such as breathing, digesting food, and
heart and gland functions.
Introduction

5. • Although some neuropathies may affect all
three types of nerves, others primarily
affect one or two types.
– Therefore, terms such as
• predominately motor neuropathy
• predominately sensory neuropathy
• sensory-motor neuropathy
• autonomic neuropathy
– are often used to describe a patient's
condition.
Introduction

6. • Because every peripheral nerve has a
highly specialized function in a specific
part of the body, a wide array of symptoms
can occur when nerves are damaged.
• Some people may experience temporary
numbness, tingling, and pricking
sensations (paresthesia), sensitivity to
touch, or muscle weakness.
Introduction

7. • Others may suffer more extreme
symptoms, including burning pain
(especially at night), muscle wasting,
paralysis, or organ or gland dysfunction.
Introduction

8. • People may become unable to digest food
easily, maintain safe levels of blood
pressure, sweat normally, or experience
normal sexual function.
• In the most extreme cases, breathing may
become difficult or organ failure may
occur.
Introduction

9. • Some forms of neuropathy involve
damage to only one nerve and are called
mononeuropathies.
• More often though, multiple nerves
affecting all limbs are affected-called
polyneuropathy.
Introduction

10. • Occasionally, two or more isolated nerves
in separate areas of the body are affected-
called mononeuritis multiplex.
Introduction

11. • In acute neuropathies, such as Guillain-
Barré syndrome, symptoms appear
suddenly, progress rapidly, and resolve
slowly as damaged nerves heal.
• In chronic forms, symptoms begin subtly
and progress slowly.
Introduction

12. • Some people may have periods of relief
followed by relapse.
• Others may reach a plateau stage where
symptoms stay the same for many months
or years.
Introduction

13. • Some chronic neuropathies worsen over
time, but very few forms prove fatal unless
complicated by other diseases.
• Occasionally the neuropathy is a symptom
of another disorder.
Introduction

14. • In the most common forms of
polyneuropathy, the nerve fibers most
distant from the brain and the spinal cord
malfunction first.
• Pain and other symptoms often appear
symmetrically, for example, in both feet
followed by a gradual progression up both
legs.
Introduction

15. Introduction
• Next, the fingers, hands, and arms may
become affected, and symptoms can
progress into the central part of the body.
• Many people with diabetic neuropathy
experience this pattern of ascending nerve
damage.

16. Anatomy
• The body’s nervous system is made up of
two parts.
– The central nervous system (CNS)
– The peripheral nervous system (PNS)

17. Anatomy
• The peripheral nerves include:
– cranial nerves
• (with the exception of the second)
– spinal nerve roots
– dorsal root ganglia
– peripheral nerve trunks and their terminal
branches
– peripheral autonomic nervous system

18. Diagnostic Approach
• The differential diagnosis of peripheral
neuropathy is significantly narrowed by a
focused clinical assessment that addresses
several key issues –
– Does the patient actually have a neuropathy?
– What is the pattern of involvement?
– Is the neuropathy focal, multifocal or symmetric?
– If the neuropathy is symmetric, is it proximal or distal?

19. • Does the patient actually have a neuropathy?
– Causes of generalized weakness include motor
neuron disease, disorders of the neuromuscular
junction and myopathy.
– Peripheral neuropathy can also be mimicked by
myelopathy, syringomyelia or dorsal column
disorders, such as tabes dorsalis.
– Hysterical symptoms can sometimes mimic a
neuropathy.
Diagnostic Approach

20. • Is the neuropathy focal, multifocal or symmetric?
– Focal neuropathies include common compressive
neuropathies such as carpal tunnel syndrome, ulnar
neuropathy at the elbow or peroneal neuropathy at
the fibular head
– A multifocal neuropathy suggests a mononeuritis
multiplex that may be caused, for example, by
vasculitis or diabetes
Diagnostic Approach

21. • If the neuropathy is symmetric, is it proximal or
distal?
– Most toxic and metabolic neuropathies present as a
distal symmetric or dying-back process.
– Proximal sensory neuropathies are rare and include
porphyria.
– Predominantly motor neuropathies are often proximal
and include acquired inflammatory neuropathies such
as Guillain-Barré syndrome.
• An exception is lead neuropathy, which initially affects motor
fibers in radial and peroneal distributions.
Diagnostic Approach

22. Distal Symmetric Sensorimotor
Polyneuropathies
• Infectious diseases
– Acquired immunodeficiency
syndrome
– Lyme disease
• Sarcoidosis
• Toxic neuropathy
– Acrylamide
– Carbon disulfide
– Dichlorophenoxyacetic acid
– Ethylene oxide
– Hexacarbons
– Carbon monoxide
– Organophosphorus esters
– Glue sniffing
• Metal neuropathy
– Chronic arsenic intoxication
– Mercury
– Gold
– Thallium
• Medications (see next
slide)

23. Medications Causing Neuropathies
• Axonal
Vincristine (Oncovin, Vincosar
PFS)
Paclitaxel (Taxol)
Nitrous oxide
Colchicine (Probenecid, Col-
Probenecid)
Isoniazid (Laniazid)
Hydralazine (Apresoline)
Metronidazole (Flagyl)
Pyridoxine (Nestrex, Beesix)
Didanosine (Videx)
Lithium
Alfa interferon (Roferon-A, Intron
A, Alferon N)
Dapsone
• Axonal - continued..
Phenytoin (Dilantin)
Cimetidine (Tagamet)
Disulfiram (Antabuse)
Chloroquine (Aralen)
Ethambutol (Myambutol)
Amitriptyline (Elavil, Endep)
• Demyelinating
Amiodarone (Cordarone)
Chloroquine
Suramin (Fourneau 309, Bayer
205, Germanin)
Gold
• Neuronopathy
Thalidomide (Synovir)
Cisplatin (Platinol)
Pyridoxine

24. Proximal Symmetric Motor
Polyneuropathies
– Guillain-Barré syndrome
– Chronic inflammatory demyelinating polyradiculoneuropathy
– Diabetes mellitus
– Porphyria
– Osteosclerotic myeloma
– Waldenstrom's macroglobulinemia
– Monoclonal gammopathy of undetermined significance
– Acute arsenic polyneuropathy
– Lymphoma
– Diphtheria
– HIV/AIDS
– Lyme disease
– Hypothyroidism
– Vincristine (Oncovin, Vincosar PFS) toxicity

25. • Neuropathies can be categorized
according to the fiber type that is primarily
involved.
• Most toxic and metabolic neuropathies are
initially sensory and later may involve the
motor fibers.
Diagnostic Approach

26. • Pure sensory neuropathies can result from
drug toxicity (e.g., thalidomide, cisplatin
[Platinol]), paraneoplastic syndromes or
nutritional deficiencies.
• Primarily motor neuropathies include
Guillain-Barré syndrome.
Diagnostic Approach

27. • Alcoholism and diabetes can both cause
small-fiber, painful neuropathies
Diagnostic Approach

28. • Autonomic involvement occurs in many
small-fiber neuropathies but can also
occur in Guillain-Barré syndrome and is
sometimes life-threatening.
Diagnostic Approach

29. • It is important to distinguish whether the
neuropathy is axonal, demyelinating, or
both.
• This differentiation is best achieved using
nerve conduction studies (NCS) and
electromyography (EMG).
Diagnostic Approach

30. • Diabetes, HIV infection and alcoholism can
cause several patterns of neuropathy.
• They most commonly cause a distal, symmetric
axonal sensorimotor neuropathy.
• The second most common presentation in these
conditions is a small-fiber, painful neuropathy.
Diagnostic Approach

31. History
• The temporal course of a neuropathy varies,
based on the etiology.
– With trauma or ischemic infarction, the onset will be
acute, with the most severe symptoms at onset.
– Inflammatory and some metabolic neuropathies have
a subacute course extending over days to weeks.
– A chronic course over weeks to months is the
hallmark of most toxic and metabolic neuropathies.

32. History
• A chronic, slowly progressive neuropathy
over many years occurs with most
hereditary neuropathies or with chronic
inflammatory demyelinating
polyradiculoneuropathy (CIDP).
• Neuropathies with a relapsing and
remitting course include Guillain-Barré
syndrome.

33. • Ischemic neuropathies often have pain as
a prominent feature.
• Small-fiber neuropathies often present
with burning pain, lightning-like or
lancinating pain, aching, or uncomfortable
paresthesias (dysesthesias).
History

34. • Dying-back (distal symmetric axonal)
neuropathies initially involve the tips of the
toes and progress proximally in a stocking-
glove distribution.
History

35. • Peripheral neuropathy can present as
restless leg syndrome.
• Proximal involvement may result in
difficulty climbing stairs, getting out of a
chair, lifting and swallowing, and in
dysarthria.
History

36. • The clinical assessment should include:
– careful past medical history, looking for
systemic diseases that can be associated with
neuropathy, such as diabetes or
hypothyroidism.
History

37. • Many medications can cause a peripheral
neuropathy, typically a distal symmetric
axonal sensorimotor neuropathy.
• Detailed inquiries about drug and alcohol
use, as well as exposure to heavy metals
and solvents, should be pursued.
History

38. • All patients should be questioned
regarding
– HIV risk factors
– foreign travel (leprosy)
– diet (nutrition)
– vitamin use (especially B6)
– possibility of a tick bite (Lyme disease)
History

39. • The review of systems may provide clues
regarding other organ involvement and the
presence of an underlying malignancy.
History

40. Differential Diagnosis of Neuropathies by Clinical
Course
Acute onset
(within days)
Subacute onset
(weeks to months)
Chronic
course/
insidious
onset
Relapsing/
remitting
course
Guillain-Barré
syndrome
Maintained exposure to
toxic
agents/medications
Hereditary motor
sensory
neuropathies
Guillain-Barré
syndrome
Acute intermittent
porphyria
Persisting nutritional
deficiency
Dominantly
inherited sensory
neuropathy
CIDP
Critical illness
polyneuropathy
Abnormal metabolic
state
CIDP HIV/AIDS
Diphtheric
neuropathy
Paraneoplastic
syndrome
Toxic
Thallium toxicity CIDP Porphyria

41. Physical Examination
• A cranial nerve examination can provide
evidence of mononeuropathies or proximal
involvement.
• Funduscopic examination may show
abnormalities such as optic pallor, which
can be present in leukodystrophies and
vitamin B12 deficiency.

42. • Direct strength testing of muscles
enervated by cranial nerves V, VII, IX/X, XI
and XII is important, as mild bilateral
weakness can be missed by observation
only.
Physical Examination

43. • The motor examination includes a search
for fasciculations or cramps, or loss of
muscle bulk.
• Tone is normal or reduced.
Physical Examination

44. • The pattern of weakness helps narrow the
diagnosis: symmetric or asymmetric, distal
or proximal, and confined to a particular
nerve, plexus or root level.
Physical Examination

45. • Deep tendon reflexes are reduced or
absent.
• A bilateral foot drop may result in a
steppage gait in which the patient must lift
the knees very high in order to clear the
toes.
• Proximal weakness results in an inability
to squat or to rise unassisted from a chair.
Physical Examination

46. • The general physical examination can
provide evidence of orthostatic
hypotension without a compensatory rise
in heart rate when autonomic fibers are
involved.
Physical Examination

47. • Respiratory rate and vital capacity should
be evaluated in Guillain-Barré syndrome to
assess for respiratory compromise.
• The presence of lymphadenopathy,
hepatomegaly or splenomegaly, and skin
lesions may provide evidence of systemic
disease.
Physical Examination

48. • Pale transverse bands in the nail beds,
parallel to the lunula (Mees' lines), suggest
arsenic poisoning.
Physical Examination

49. Laboratory Evaluation
• EMG and nerve conduction studies (NCS)
are often the most useful initial laboratory
studies in the evaluation of a patient with
peripheral neuropathy

50. • They can confirm the presence of a
neuropathy and provide information as to
the type of fibers involved (motor, sensory,
or both), the pathophysiology (axonal loss
versus demyelination) and a symmetric
versus asymmetric or multifocal pattern of
involvement.
Laboratory Evaluation

51. • The limitations of EMG/NCS should be taken
into account when interpreting the findings.
– There is no reliable means of studying proximal
sensory nerves.
– NCS results can be normal in patients with small-fiber
neuropathies
– Lower extremity sensory responses can be absent in
normal elderly patients.
• EMG/NCS are not substitutes for a good clinical
examination.
Laboratory Evaluation

52. • Subsequent studies should be tailored to the most likely
diagnostic possibilities, and to the acuteness and
severity of the neuropathy.
• With an acute progressive neuropathy, a neurologic
consultation early in the course of the evaluation is
essential.
• Further evaluation of these patients includes EMG/NCS,
lumbar puncture, chest radiograph, electrocardiogram
and determination of forced vital capacity.
Laboratory Evaluation

53. • The most common presentation is that of a distal
symmetric sensorimotor neuropathy.
• Initial evaluation should include:
– fasting serum glucose, glycosylated hemoglobin,
blood urea nitrogen, creatinine, complete blood cell
count, erythrocyte sedimentation rate, urinalysis,
vitamin B12 and thyrotropin stimulating hormone
levels.
– Neurologic assessment may be warranted if the initial
evaluation does not produce a diagnosis.
Laboratory Evaluation

54. • CSF is useful in evaluation of
myelinopathies and polyradiculopathies.
• An elevated total protein level with < 5
wbc(albuminocytologic dissociation) is
present in acquired inflammatory
neuropathy (e.g., Guillain-Barré syndrome,
CIDP).
Laboratory Evaluation

55. • Other studies useful in specific clinical
contexts are:
– cytology (lymphoma)
– special studies
• such as Lyme polymerase chain reaction and
cytomegalovirus branched chain DNA
(polyradiculopathy or mononeuritis multiplex in
AIDS).
Laboratory Evaluation

56. • Nerve biopsy is only helpful in very
specific cases to diagnose vasculitis,
leprosy, amyloid neuropathy,
leukodystrophies, sarcoidosis and,
occasionally, CIDP.
Laboratory Evaluation

57. • It can be difficult to document a small-fiber
neuropathy because the only
abnormalities on neurologic examination
may be loss of pinprick and temperature
sensation in a distal distribution.
Laboratory Evaluation

58. • EMG/NCS may be normal.
• Autonomic studies are only helpful if the
autonomic fibers are involved.
• As a result, small-fiber neuropathy
remains a primarily clinical diagnosis.
Laboratory Evaluation

59. • The evaluation should include the most
likely causes (i.e., diabetes, alcoholism,
AIDS).
• If these studies are normal, a neurologic
consultation is recommended.
Laboratory Evaluation

60. Treatment
• The goal of treatment is to manage the
underlying condition causing the
neuropathy and repair damage, as well as
provide symptom relief.

61. Treatment
• Controlling a chronic condition may not
eliminate the neuropathy, but it can play a
key role in managing it.

62. Treatment
• Neuropathic pain is often difficult to control.
• Medications :
– OTC analgesics .
– antiepileptic drugs, including gabapentin, phenytoin,
and carbamazepine
– some classes of antidepressants, including tricyclics
such as amitriptyline.
– Mexiletine
– local anesthetics such as lidocaine or topical patches
containing lidocaine
– Codeine/oxycodone

63. • Mechanical aids can help reduce pain and lessen the
impact of physical disability.
– Hand or foot braces can compensate for muscle weakness or
alleviate nerve compression.
– Orthopedic shoes can improve gait disturbances and help
prevent foot injuries in people with a loss of pain sensation.
• If breathing becomes severely impaired, mechanical
ventilation can provide essential life support.
Treatment

64. • Surgical intervention often can provide
immediate relief from mononeuropathies caused
by compression or entrapment injuries.
– Repair of a slipped disk can reduce pressure on
nerves where they emerge from the spinal cord; the
removal of benign or malignant tumors can also
alleviate damaging pressure on nerves.
– Nerve entrapment often can be corrected by the
surgical release of ligaments or tendons.
Treatment

65. Questions ???