Peripheral nerve

disorders

Dr. Mehzabin Ahmed

Diseases of the peripheral nerves

Patients suffering from a peripheral nerve disease have

 motor problems (muscle weakness) or
 sensory disturbances (parasthesia, loss of sensation,
tingling, numbness) or
 a combination of both.
 Symptoms may be confined to one nerve or a group of
nerves in either symmetric or an asymmetric fashion.
 Neuralgia is the pain in the distribution of a nerve or nerves eg.
sciatica , shingles.
 Neuritis is a term used to describe the inflammation of the
nerves.
 Neuropathy is a term used to describe the disturbed function or
a pathological change in the nerve.
 Trauma may also cause nerve injury, which is classified as:
 Neuropraxia- is a block in the nerve conduction through an

axon with no anatomical interruption in the continuity of the

axon.
 Axonotmesis-is the anatomical interruption of the axon with

no or only partial interruption of the connective tissue

framework.
 Neurotmesis- is a complete anatomical disruption of the

axon and all of the surrounding connective tissue (ruptured

nerve).
General Clinical Patterns of Involvement

There are a variety of patterns that clinical symptoms

may manifest.
 Mononeuropathy
 Mononeuropathy multiplex or multifocal neuropathy
 Polyneuropathy
 Mononeuropathy
 This denotes focal involvement of a single nerve trunk.
 A localized neuropathy usually implies a local causation, such as
trauma or nerve entrapment as in:
 Ulnar neuropathy causes claw hand
 Dorsal root ganglia in herpes zoster
 Median nerve involvement- carpal tunnel syndrome
 Facial nerve involvement- Bell’s palsy
 Distal tibial nerve involvement- tarsal tunnel syndrome
 Peroneal neuropathy- foot drop
 In Leprosy, neuritis of any superficial nerve can be seen like the
median, ulnar, peroneal, facial nerve.
 Mononeuropathy multiplex or multifocal neuropathy
This denotes simultaneous or sequential involvement of two or more
nerves, usually not contiguously.
It implies local affection of multiple nerves, and may be due to a
generalized process such as:
 Vasculitis- polyarteritis nodosa
 Multiple myeloma
 HIV
 Mixed cryoglobulinemia
 Mixed connective tissue disorder
 Sarcoidosis
 Multifocal CIPD (chronic inflammatory demyelinating
polyneuropathy)
 Leprosy
 Multifocal type of diabetic neuropathy
 Amyloidosis
Polyneuropathy

 This is a generalized asymmetric involvement

of peripheral nerves usually associated with a
systemic disorder.
 It is further classified as:
 Neuronopathy
 Myelinopathy
 Axonopathy
Neuronopathy

 When the primary site of injury is the neurons, eg:

 Poliomyelitis- anterior horn cells are involved

 Herpes zoster- trigeminal ganglion is affected
 Diphtheritic- sensory ganglia
 Carcinomatosis- as in paraneoplastic syndromes
 Axonopathy
 Axonal degeneration occurs first
 Secondary demyelination is seen
 It is often symmetric in distribution, giving a "stocking-glove"
pattern of motor and/or sensory loss.
 Causes:
 Diphtheria ,
 Porphyria ,
 Industrial chemical exposure,
 Drugs ,
 Metabolic disease (diabetes mellitus, uremia),
 Nutritional deficiency of Vitamin B 2,6,12,
 Alcoholism ,
 Hereditary motor and sensory neuropathies.
Myelinopathy
 When the primary event is the segmental demyelination with
the preservation of the axons.
 Two main disorders that fall into this category are the Guillian
Barré syndrome and the chronic inflammatory Demyelinating
polyneuropathy.
 These are immune disorders where antibodies reacting with
antigens present on the peripheral nerves elicit an
inflammatory reaction that destroys myelin and axons.
 Other disorders are multiple myeloma, cancers, HIV, HMSN
(hereditary motor and sensory neuropathy)
Early peripheral neuropathy Late peripheral neuropathy
Classification of peripheral nerve diseases
 The categories into which nerve diseases may fall.
 Metabolic and toxic neuropathies
 Vasculitic neuropathies
 Inflammatory neuropathies
 Hypertrophic neuropathies
 Genetic neuropathies
 Infectious neuropathies
 Metabolic and toxic neuropathies
 Usually associated with axonal degeneration, with varying
degrees of secondary demyelination.
 Causes:
 Some of the metabolic disorders associated with neuropathy
include diabetes mellitus, vitamin deficiency, uremia, and
prophyria.
 Exogenous toxins that have been associated with neuropathy
include alcohol, vincristine, isoniazid, arsenic, lead, hexane,
hexachlorophene, acrylamide, and triethyltin.
 Inherited lysosomal storage disorders also have neuropathy
as a component of the systemic metabolic defect.
 Vasculitic neuropathies
 Usually present as a subacute mononeuropathy multiplex,
or symmetric polyneuropathy
 The lesions in peripheral nerve are due to ischemia, and
frank infarction may be present.
 Causes:
 Polyarteritis nodosa,
 Churg-Strauss syndrome, and
 Rheumatoid arteritis
Inflammatory neuropathies:
 Immune mediated damage.
 Present as an acute paralytic illness.
 Acute inflammatory demyleinating polyneuropathy, or
Guillain-Barre syndrome, may present as an acute
paralytic illness.
 Chronic inflammatory demyelinating polyneuropathy
has either a relapsing/remitting or chronic progressive
course (may cause a severe disability, in chronic
cases axonal loss may also occur in addition to the
Demyelination).
 Hypertrophic neuropathies

 These disorders are united by a characteristic pathologic

feature - the presence of "onion bulbs”-multiple Schwann
cell processes concentrically surrounding either individual
or small groups of fibers.
 This hypertrophy may be so severe as to cause palpable
enlargement of affected nerves.
 Hypertrophic neuropathies (contd)
Causes:
 Chronic relapsing polyneuropathies, where multiple bouts of
demyelination and remyelination occur;
 Long-standing diabetic neuropathy; and

 Genetically inherited conditions such as

 Charcot-Marie-Tooth disease
- Autosomal dominant disorder
- weakness and atrophy of the distal muscles- especially
those innervated by the peroneal nerve thus giving a
stork leg appearance,
- pes cavus,
- sensory loss and action tremors.
- slowly progressive and is compatible with a normal life,
 Dejerine-Sottas neuropathy,
 Refsum's disease.
 Pes cavus- high arched foot

Stork like deformity of

the legs

Upper limbs and hands are involved in

later stages
 Genetic neuropathies:
 A wide variety of disorders may be placed in this
category, including the
 inherited hypertrophic neuropathies described above,
 some forms of leukodystrophy (metachromatic
leukodystrophy is one example),
 ataxia-telangiectasia, and
 giant axonal neuropathy.

Infectious neuropathies:
 A wide variety of pathogens may infect nerve.
 More common causes include
 herpes zoster neuritis, and
 in the third world, leprosy & poliomyelitis.
Shingles in Varicella-Zoster infection Thickened nerves in leprosy
 Diabetic Neuropathies
 Diabetic neuropathies are heterogeneous group of disorders
that may be clinically classified into 4 major groups:
2. Distal symmetric primarily sensory neuropathy
(polyneuropathy)
3. Autonomic neuropathy
4. Proximal asymmetric painful primarily motor neuropathy
(also known as diabetic amyotrophy)
5. Cranial mononeuropathy
 Both diabetic polyneuropathy and the autonomic
neuropathy of diabetes are thought to be due to metabolic
abnormalities.
 Chronic hyperglycemia activates the pathway in nerve
tissue that reduce the sodium-potassium-ATPase activity,
which is critical for nerve function.
 Thus the nerve conduction is altered and eventually also
results in structural nerve changes, like demyelination - in
this case, it is a form of secondary demyelination.
 Diabetic amyotrophy and cranial neuropathies are thought
to be due to focal ischemic lesions on the basis of the
vascular disease- diabetic microangiopathy
The most common neuropathy in clinical

practice is diabetic neuropathy

Inherited neuropathies
 They are rare and include
 Lysosomal storage diseases,
 familial Amyloidosis,
 the neuropathies in these diseases is a component or
symptom of the systemic metabolic defect.
 Diseases that cause neurogenic atrophy
 Neurogenic atrophy occurs when there is interruption of the
normal innervation of muscle.
 This can occur at the level of
 the anterior horn cell, or

 the axon.

 the neuromuscular junction as with myasthenia gravis.

 Many disease processes may result in neurogenic atrophy, like:

 Anterior horn cell disorders:

1. Poliomyelitis
2. Amyotrophic lateral sclerosis
3. In infants, spinal muscular atrophy, which is also known
as Werdnig-Hoffman disease
 Axonal abnormalities. These include peripheral neuropathies and
traumatic transections. 20
 Following the loss of innervation, myofibers atrophy and
become small and angular.
 The appearance of the entire muscle will depend upon the
number of motor units involved in the initial injury.
 If there is only partial denervation and only scattered motor
units are involved, the initial stages of denervation atrophy
will be characterized by scattered, atrophic myofibers This
is because myofibers from an individual motor unit are
randomly distributed throughout a muscle fiber.
 When the nerve regenerates the reinnervated fibers regain
their normal appearance.
 With repetitive or severe denervation, entire fascicles of
myofibers may become atrophic, producing the pattern of
fascicular atrophy.
 Spinal muscular dystrophy: Syn: infantile motor
neurone disease
 It is a congenital disorder inherited by the Autosomal recessive
mode.
 It begins in the childhood/ adolescence causing muscle weakness.

 Widespread atrophy is noted involving entire fascicles-

panfascicular with a few scattered enlarged myocyte fibres.
Four main forms are seen
 Type 1: Werdnig- Hoffman disease- rapidly progressing form
sometimes present since birth or onset is before 3mths of age
 Type 2: More slowly progressing, seen in infants and children
between 6-12mths. It causes severe disability.
 Type 3: Kugelberg Welander disease- Slow progression with
onset at 2-15 years and lives upto adult life. The disability is mild to
moderate.
 Type 4: Very slow progression with mild disability. The patients are
usually adults.the progression may stop after several decades.
 Myasthenia Gravis
Pathology and pathogenesis
 Myasthenia gravis is an autoimmune disorder

 presence of antibodies against acetylcholine

receptors in the neuromuscular junction, (IgG and C3
can be found at postsynaptic muscle membranes).
 It is thought that antibodies to the acetylcholine

receptor function either by blocking the receptor or by

causing its degradation.
Clinical

findings
Myasthenia gravis is an autoimmune disease, clinically characterized by
 muscle weakness and fatigability.
 Weakness is generally worst at the end of the day, and
particularly affects extraocular and facial muscles.
 The disease can be mild and restricted, or generalized,
catastrophic and fatal.
 There are two groups of susceptible individuals: young women their
twenties, and older men before the age of 70.
 Younger women tend to be HLA-B8 positive and have thymic
hyperplasia,
 older male patients are more likely to have thymoma and
characteristically worsening of symptoms with repetitive
stimulation of motor nerves.
 Patients will also show a response to anticholinesterase agents, which is
the basis of the Tensilon test (with edrophonium, the patient improves).
Eaton-Lambert Syndrome
 Eaton-Lambert syndrome is a syndrome in which patients
display weakness in proximal limb muscles.
 an improvement in the symptoms in response to repetitive
stimulation on EMG.
 impaired release of acetylcholine at nerve terminals.
 Eaton- Lambert syndrome is caused by antibodies directed
against calcium channels found on the surface of small cell
carcinoma which cross-react with similar channels on
presynaptic terminals
 It is a paraneoplastic syndrome seen in small cell
carcinoma
Summary

 Terminology
 Patterns of peripheral nerve involvement
 Mononeuropathy
 Multifocal neuropathy
 Polyneuropathy-
 Neuronopathy
 Myelinopathy
 Axonopathy
Summary
 Causes of PN Diseases:
 Metabolic & toxic neuropathies- diabetic neuropathy
 Vascular neuropathies
 Inflammatory neuropathies
 Hypertrophic neuropathies
 Genetic neuropathies
 Infectious neuropathies
 Inherited neuropathies
 Neurogenic atrophy:
 Spinal muscular dystrophy
 Myaesthenia gravis
 Eaton- Lambert syndrome