Peripheral Nerve Disorders

Peripheral nerve disorders Dr. Mehzabin Ahmed

Diseases of the peripheral nerves Patients suffering from a peripheral nerve disease have 

motor problems (muscle weakness) or

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sensory disturbances (parasthesia, loss of sensation, tingling, numbness) or

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a combination of both.

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Symptoms may be confined to one nerve or a group of nerves in either symmetric or an asymmetric fashion.

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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

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Mononeuropathy multiplex or multifocal neuropathy

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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

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Dorsal root ganglia in herpes zoster

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Median nerve involvement- carpal tunnel syndrome

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Facial nerve involvement- Bell’s palsy

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Distal tibial nerve involvement- tarsal tunnel syndrome

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Peroneal neuropathy- foot drop

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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:       

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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 

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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

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Secondary demyelination is seen

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It is often symmetric in distribution, giving a "stocking-glove" pattern of motor and/or sensory loss.

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Causes: 

Diphtheria ,

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Porphyria ,

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Industrial chemical exposure,

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Drugs ,

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Metabolic disease (diabetes mellitus, uremia),

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Nutritional deficiency of Vitamin B 2,6,12,

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Alcoholism ,

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Hereditary motor and sensory neuropathies.

Myelinopathy 

When the primary event is the segmental demyelination with the preservation of the axons.

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Two main disorders that fall into this category are the Guillian Barré syndrome and the chronic inflammatory Demyelinating polyneuropathy.

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These are immune disorders where antibodies reacting with antigens present on the peripheral nerves elicit an inflammatory reaction that destroys myelin and axons.

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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

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Vasculitic neuropathies

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Inflammatory neuropathies

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Hypertrophic neuropathies

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Genetic neuropathies

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Infectious neuropathies

Metabolic and toxic neuropathies 

Usually associated with axonal degeneration, with varying degrees of secondary demyelination.

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Causes: 

Some of the metabolic disorders associated with neuropathy include diabetes mellitus, vitamin deficiency, uremia, and prophyria.

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Exogenous toxins that have been associated with neuropathy include alcohol, vincristine, isoniazid, arsenic, lead, hexane, hexachlorophene, acrylamide, and triethyltin.

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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

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The lesions in peripheral nerve are due to ischemia, and frank infarction may be present.

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Causes: 

Polyarteritis nodosa,

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Churg-Strauss syndrome, and

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Rheumatoid arteritis

Inflammatory neuropathies: 

Immune mediated damage.

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Present as an acute paralytic illness. 

Acute inflammatory demyleinating polyneuropathy, or Guillain-Barre syndrome, may present as an acute paralytic illness.

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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

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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.

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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 

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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

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Genetic neuropathies: A wide variety of disorders may be placed in this category, including the  

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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

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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:

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Distal

symmetric

primarily

sensory

neuropathy

(polyneuropathy) 3.

Autonomic neuropathy

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Proximal asymmetric painful primarily motor neuropathy (also known as diabetic amyotrophy)

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Cranial mononeuropathy

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Both diabetic polyneuropathy and the autonomic neuropathy of diabetes are thought to be due to metabolic abnormalities.

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Chronic hyperglycemia activates the pathway in nerve tissue that reduce the sodium-potassium-ATPase activity, which is critical for nerve function.

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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.

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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,

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familial Amyloidosis,

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the neuropathies in these diseases is a component or symptom of the systemic metabolic defect.

Diseases that cause neurogenic atrophy 

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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:

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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

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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 fasciclespanfascicular 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

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There are two groups of susceptible individuals: young women their twenties, and older men before the age of 70. 

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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. 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.

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an improvement in the symptoms in response to repetitive stimulation on EMG.

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impaired release of acetylcholine at nerve terminals.

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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

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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:       

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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