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

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

Mononeuropathy multiplex or multifocal neuropathyThis 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.

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.

Hypertrophic neuropathies (contd)

Stork like deformity of the legs

Upper limbs and hands are involved in later stages

Pes cavus- high arched foot

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:

1. Distal symmetric primarily sensory neuropathy

(polyneuropathy)

2. Autonomic neuropathy

3. Proximal asymmetric painful primarily motor neuropathy

(also known as diabetic amyotrophy)

4. 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 GravisPathology 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

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

Summary