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Neurology
Channel |
Peripheral Neuropathy
Keywords: autonomic dysfunction; dysesthesias; muscle atrophy; numbness; pain; paresthesias; sensory ataxia; weakness
Historical note and nomenclature
The peripheral neuropathies are a diverse group
of disorders that affect the peripheral nerves. They may be acquired or
hereditary, systemic in origin or restricted to the peripheral nerves,
and mildly annoying or disabling and severe.
Clinical manifestation
The clinical manifestations of neuropathy depend
on the type and distribution of the nerve populations that are
affected,
the degree to which they are damaged, and the course of the disease.
When
the motor nerves are damaged, the neuropathy manifests as weakness and
muscle atrophy. Damage to sensory nerves can cause loss of sensation,
paresthesias and dysesthesias, pain, and sensory ataxia. Autonomic
dysfunction can result in postural hypotension, impotence,
gastrointestinal and genitourinary dysfunction, abnormal sweating, and
hair loss. Involvement of small unmyelinated fibers in sensory
neuropathy typically results in loss of pin prick and temperature
sensations, numbness, and painful burning, cold, stinging, or tingling
paresthesias. Large fiber sensory involvement can manifest as loss of
vibration and position sensations, sensory ataxia, and numbness or
tingling paresthesias. Demyelinating neuropathies primarily affect the
myelin sheaths, whereas axonal neuropathies target the peripheral nerve
axons. Deep tendon reflexes are frequently diminished or absent,
particularly in the demyelinating neuropathies. Since most nerve trunks
are mixed, damage to the peripheral nerves often affects more than one
of these functions.
Polyneuropathy usually refers to diffuse
involvement of the peripheral nerves, and is usually first noted
distally in the hands and feet. Mononeuropathy or radiculopathy refers
to involvement of a single nerve or nerve root, respectively, and
mononeuropathy multiplex signifies focal involvement of two or more
nerves. The term Neuritis is usually restricted to inflammatory
conditions. Neuronopathy refers to primary involvement of the nerve
cell body, rather than its axon, and ganglioneuritis refers to
inflammatory involvement of the nerve cell bodies, usually in the
sensory or autonomic ganglia. Plexopathy or plexitis refers to
involvement of a
nerve plexus, as in brachial or lumbosacral plexitis.
Neuropathies are classified according to the
clinical syndrome, pathological features, or etiology. A classification
of the peripheral neuropathies is presented in the differential
diagnosis section.
Etiology
The etiology of peripheral neuropathies is
diverse and includes infection, heredity, trauma and entrapment, cold,
toxins, certain nutrients and drugs, radiation, critical illness,
endocrine and renal diseases, as well as idiopathic, paraneoplastic,
and immune-mediated and inflammatory causes.
Biological basis
The peripheral nervous system is made up of
anatomically and functionally distinct neuronal populations, along with
their processes and supportive tissues, which subserve its various
motor, sensory, and autonomic functions. The motor nerves innervate
skeletal muscle and are responsible for motor movement. Their cell
bodies or perikarya lie in the anterior horn of the spinal cord, and
their axons travel through the anterior spinal roots and peripheral
nerve trunks to terminate at the neuromuscular junction.
The sensory nerves convey sensory messages from the skin and internal
organs. Their cell bodies lie in sensory ganglia along the spinal cord
in the spinal canal, and their processes extend from the receptor
organs in the periphery, through the dorsal roots, and into the spinal
cord. The autonomic nerves
innervate the heart, glands, and smooth muscles. They consist of
preganglionic
fibers that emanate from the brainstem and spinal cord, and
postganglionic
fibers that emanate from the sympathetic ganglia on either side of the
vertebral column or from parasympathetic ganglia that lie adjacent
their target organs. The various elements of the peripheral nerves are
interconnected and communicate with the spinal cord and each other
through their processes, which span
the body similarly to a fine electrical network.
The neuronal processes, or axons, travel as
bundles within fascicles in the peripheral nerves. Individual axons are
separated or enveloped by Schwann cell processes or myelin sheaths, and
are embedded in a loose matrix of connective tissue called the
endoneurium. Each fascicle is surrounded by a dense band of connective
tissue called the perineurium, which also acts as a blood-nerve barrier
and helps maintain the specialized endoneurial environment necessary
for nerve function. The entire peripheral nerve system is ensheathed by
a dense collagenous layer called the epineurium, through which blood
vessels and lymphatic drainage provide nutrients and drainage to the
nerves.
Nerve signals are propagated by the axonal
membrane. Myelinated axons can conduct impulses faster and at higher
frequencies than unmyelinated axons. Each myelinating Schwann cell
ensheathes an axon segment of 500 to 1500 µm in length called an
internode. Adjacent internodes are separated by 1 µm unmyelinated
axonal segments called nodes of
Ranvier. The myelinated fibers conduct impulses from node to node, with
the
internodal membranes remaining relatively inert. If demyelination
occurs,
conductions are slowed or blocked. Unmyelinated fibers conduct slowly
but
continuously along their entire length.
Epidemiology
Peripheral neuropathies are thought to be common,
although epidemiologic studies are scarce. Studies that are available
suggest that 2.4% to 8% of adults may have some form of neuropathy. The
most common cause of neuropathy is diabetes, which may account for
approximately one third
of all neuropathies, with the remaining two thirds split between
idiopathic and all other known causes.
Prevention
Preventative measures vary according to the type
of peripheral neuropathy.
Differential Diagnosis
A Classification of the Peripheral Neuropathies
I. Neuropathies associated with endocrine and
renal diseases
A. Diabetic neuropathies
• Distal symmetric diabetic polyneuropathy
• Autonomic neuropathy
• Lumbosacral plexopathy or amyotrophy
• Mononeuritis or mononeuritis multiplex,
including cranial neuropathies
and radiculopathies
B. Neuropathy of renal disease
C. Hypothyroid neuropathy
II. Immune-mediated or inflammatory neuropathies
A. Acute inflammatory polyneuropathies
(Guillain-Barré syndrome and variants)
Acute inflammatory demyelinating polyneuropathy
(AIDP or Guillain-Barré
syndrome)
Acute motor axonal neuropathy
Acute motor and sensory axonal neuropathy
Miller-Fisher syndrome
Acute sensory neuropathy or ganglioneuritis
Acute autonomic neuropathy (Pandysautonomia)
B. Chronic inflammatory polyneuropathies
Chronic inflammatory demyelinating polyneuropathy
Demyelinating neuropathy associated with
anti-MAG antibodies
Multifocal motor neuropathy
Sensory neuropathy associated with anti-GD1b and
disialosyl ganglioside
antibodies
Sensory neuropathy associated with antisulfatide
antibodies
Sensory neuronopathy or ganglioneuritis
Paraneoplastic sensory neuropathy associated
with anti-HU antibodies
Chronic inflammatory axonal neuropathy
Vasculitic Neuropathy, nonsystemic or associated
with systemic disease
Sarcoid neuropathy
C. Plexopathies
Brachial plexitis
Lumbosacral plexitis
III. Infectious Neuropathies
A. Neuropathies caused by viruses
Cytomegalovirus
Herpes simplex
Herpes zoster (shingles)
Hepatitis C
Hepatitis B
Human immunodeficiency virus type 1
Distal symmetric sensory or sensorimotor
neuropathy
Acute and chronic inflammatory
demyelinating polyneuropathies
Mononeuropathy multiplex
Autonomic neuropathy
B. Neuropathies caused by bacteria or parasites
Borrelia burgdorferi (Lyme disease)
Corynebacterium diphtheria (Diphtheria)
Mycobacterium leprae (leprosy)
Trypanosoma cruzi (Chagas disease)
IV. Neuropathies associated with tumors,
paraneoplastic neuropathies
Sensory neuropathy associated with anti-HU
antibodies
Paraneoplastic motor neuropathy
Myeloma neuropathy and POEMS syndrome
Primary amyloidosis
Neuropathies associated with IgM monoclonal
gammopathies
Late sensorimotor neuropathy in advanced cancer
Mononeuropathy or mononeuropathy multiplex
V. Hereditary neuropathies (Charcot-Marie-Tooth
disease), in which the genetic
defects are known
Charcot-Marie-Tooth disease type 1A -
duplication of peripheral myelin
protein-22
Charcot-Marie-Tooth disease type 1B - mutation
in myelin protein zero
glycoprotein
Hereditary neuropathy with predisposition to
pressure palsy - deletion or
mutations in PMP22
Charcot-Marie-Tooth disease type X - mutation in
Connexin 22
Hereditary amyloid neuropathy - mutation in
transthyretin
Dejerine-Sottas disease - deletions or mutations
in PMP22 or myelin protein
zero
VI. Traumatic and entrapment neuropathies
Carpal tunnel syndrome
Cervical or lumbosacral radiculopathies
Median nerve at elbow
Anterior interosseous syndrome
Ulnar nerve at elbow or wrist
Radial nerve in upper arm
Sciatic nerve
Common peroneal nerve at knee
Tibial nerve at knee
Lateral cutaneous femoral nerve (meralgia
paresthetica)
Spinal accessory nerve in posterior cervical
triangle in neck
Multiple sequential mononeuropathies
VII. Cold-induced neuropathy
VIII. Toxins that cause neuropathies
Acrylamide
Arsenic
Carbon disulfide
Hexacarbon
Lead
Mercury
Organophosphates
Platinum
Thallium
IX. Nutritional causes of neuropathies
Alcohol
Thiamine (vitamin B1)
Cobalamin (vitamin B12)
Pyridoxine (vitamin B6)
Tocopherol (vitamin E)
Post gastroplasty neuropathy
X. Drugs that induce neuropathies
Chloramphenicol
Cisplatin
Colchicine
Dapsone
Disulfiram
Amiodarone (Cordarone)
Gold
Isoniazid
Misonidazole
Nitrofurantoin
Perhexiline
Propafenone
Pyridoxine (Vitamin B6)
Paclitaxel (Taxol)
Phenytoin
Simvastatin and similar cholesterol lowering
agents
Tacrolimus (FK506)
Thalidomide
Vincristine
Zalcitabine (deoxycytidine, ddC)
XI. Radiation-induced neuropathy
XII. Critical illness polyneuropathy
XIII. Idiopathic neuropathies
A. Idiopathic polyneuropathies
Idiopathic small fiber sensory neuropathy
Idiopathic large fiber sensory neuropathy
Idiopathic large and small fiber sensory
neuropathy
Idiopathic axonal sensorimotor neuropathy
Idiopathic predominantly motor axonal neuropathy
Idiopathic predominantly autonomic neuropathy
B. Idiopathic mononeuropathies
Bell's palsy
Trigeminal neuralgia
Other cranial mononeuropathies
Mononeuropathy in nonentrapment sites
Reproduced with permission from: (The Neuropathy
Association 1999)
Diagnostic Workup
A careful history provides information about the
symptoms, distribution, and course of the neuropathy. The Medical and
Social
History and Review of Systems may alert the examiner to a possible
systemic
cause such as diabetes, inflammation, or cancer, among others, or to a
toxic
or nutritional etiology. A positive family history would be suggestive
of
hereditary neuropathy. A detailed neurologic examination is required to
confirm the presence of neuropathy, and to provide information
regarding
the functional impairment, distribution, and severity of the disease.
Electrodiagnostic studies, including
electromyography and nerve conduction studies, provide further
information as to the distribution of the neuropathy, and the extent of
damage to the axons and myelin sheaths. These measures are frequently
normal in mild sensory or small fiber neuropathies, and can be detected
using Quantitative Sensory Testing or spinal somatosensory evoked
responses. Nerve and muscle biopsy can be particularly useful in the
diagnosis of autoimmune or vasculitic neuropathies, sarcoid or amyloid.
Blood
and CSF studies can aid in the diagnosis of inflammatory,
paraneoplastic, infectious, endocrine, metabolic, toxic, nutritional,
or hereditary neuropathies.
Prognosis and Complications
Prognosis and complications depend on the type
and severity of the neuropathy.
Management
Therapy is often directed at the symptoms, or
when possible, at the underlying cause of the neuropathy. Symptomatic
treatments include medical therapy for the painful paresthesias,
physical and occupational therapy to help improve mobility and
function, and supportive measures to maintain blood pressure and bowel
and bladder function if the autonomic system is involved. Treatment for
the causes of neuropathy include antibiotics or antiviral agents for
infectious neuropathies, immunomodulating agents for immune-mediated or
paraneoplastic neuropathies, improved glycemic control for diabetic
neuropathies, and surgery for compressive neuropathies, among others.
Pregnancy
Not applicable.
Anesthesia
Not applicable.