Wallerian Degeneration

Describe, including times which landmark events occur

Injury -- weakness and snesory loss is immediate

Excitability is lost in 1 week

Denervation potentials occur around 2 weeks

But regeneration begins as early as 24 hours following injury

Axon distal to the injury site degenerates, and the associated target muscle tissue is denervated --> neurolemma doesnt degenerate, but remains as a hollow tube -->

24-96 hrs after injury, proximal end of axon sprouts out toward the tube, attracted by GF's produced by schwann cells assoc. w/ the neurolemma

Neuronopathy/Gangliopathy

What is it?

What are 2 causes of sensory neuropathy?

1 cause of Motor neuropathy?

Its the loss of nerve cell bodies

Sensory neuropathy: via toxins or paraneoplasic mech

Motor neuropathy:  poliomyelitis

What is Segmental Demyelination?

3 causes?

How may secondary demyelination occur?

Def:  myelin sheath or schwann cells are damaged

Causes could be:

Immune

Metabolic

Hereditary

Secondary myelination eg: viral infection causes immune activation, potentially resulting in cross-reactivity and/or inflam that ultimately damages and destroys the myelin

Diagnostic Clues of Neuropathy in Patient History

Positive Symptoms: Define these terms:

1. Dysesthesia

2. Paresthesia

3. Allodynia

4. Neuropathic Pain

Name 2 diagnostic negative symptoms

3 other diagnostic aspects obtained from clinical interview?

Positive symptoms:

1. unpleasant abnormal sense of touch

2. tingling/numbness

3. pain due to a stim that does not normally provoke pain

4. chronic pain from NS injury

Neg:

Motor weakness

Sensory loss

Other Diagnostic clues:

Family Hx

Systemic Symptoms

Acute vs. Chronic onset

Diagnostic Clues on Examination

Describe 5 clues

1. Anatomical Pattern of localization

mononeuropathy

mononeuropathy multiplex - simultaneous or sequential involvement of individual noncontiguous nerve trunks, evolving over time, presents with acute or subacute loss of sensory/motor function of individual peripheral nerves

polyneuropathy - neurological disorder where many peripheral nerves throughout the body malfunction simultaneously

2. Motor loss vs. sensory loss vs. both

3. Proximal weakness vs. distal vs. both

4. Sensory Distribution

Glove-Stocking = sharply demarcated loss of sensory function (seen in distal diabetic neuropathy)

vs. more patchy loss

5. Small fiber affected vs. large fiber vs. both

What is Charcot-Marie-Tooth disease?

(prevalence in the US?

• Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States. 
• CMT, also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, comprises a group of disorders that affect peripheral nerves. 

What are the symptoms of Charcot-Marie-Tooth disease?

When is typical onset of symptoms?

How variable is the severity?

Progression of the disease is rapid/gradual?

Describe the range of pain and motor function

Life expectancy?

• Weakness of the foot and lower leg muscles, which may result in foot drop and a high-stepped gait with frequent tripping or falls. 
• Foot deformities, such as high arches and hammertoes (a condition in which the middle joint of a toe bends upwards) are also characteristic due to weakness of the small muscles in the feet. 
• Lower legs may take on an "inverted champagne bottle" appearance due to the loss of muscle bulk. 
• Later in the disease, weakness and muscle atrophy may occur in the hands, resulting in difficulty with fine motor skills.

Onset of symtoms:

• most often in adolescence or early adulthood, but may be delayed until mid-adulthood. 
• Severity of symptoms is quite variable in different patients and even among family members with the disease. 
• Progression of symptoms is gradual. 
• Pain can range from mild to severe, and some patients may need to rely on foot or leg braces or other orthopedic devices to maintain mobility. 
• Although in rare cases patients may have respiratory muscle weakness, CMT is not considered a fatal disease and people with most forms of CMT have a normal life expectancy.

CMT is caused by mutations in genes that produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath. Although different proteins are abnormal in different forms of CMT disease, all of the mutations affect the normal function of the peripheral nerves. Consequently, these nerves slowly degenerate and lose the ability to communicate with their distant targets.

The gene mutations in CMT disease are usually inherited, can be AD, AR, or X-linked.

How is Charcot-Marie-Tooth disease diagnosed?

Patient history, Family history, Neurological examination

Neurological examination:

• look for evidence of muscle weakness in the arms, legs, hands, and feet
• decreased muscle bulk, 
•  reduced tendon reflexes
•  sensory loss.
• Look for evidence of foot deformities, such as high arches, hammertoes, inverted heel, or flat feet. 
• (A specific sign that may be found in patients with CMT1 is hypertrophic nerves that may be felt or even seen through the skin) 

What is Guillain-Barré Syndrome?

(Whats another name for it?)

Describe its symptoms and progression

What % of cases display facial paralysis?

Prognosis?

• Guillain-Barré syndrome can affect anybody 
• Can strike at any age and both sexes are equally prone to the disorder. 
• The syndrome is rare, however, afflicting only about one person in 100,000. 

What causes Guillain-Barré syndrome?

We don't know why this non-contagious autoimmunity disease strikes some people and not others, nor do we know what sets the disease in motion, but it is associated w/ resp/GI viral infections, and occasionally surgery or vaccinations will trigger GBS

When Guillain-Barré is preceded by a viral or bacterial infection, it is possible that the virus has changed the nature of cells in the nervous system so that the immune system treats them as foreign cells. It is also possible that the virus makes the immune system itself less discriminating about what cells it recognizes as its own, allowing some of the immune cells, such as certain kinds of lymphocytes and macrophages, to attack the myelin. Sensitized T lymphocytes cooperate with B lymphocytes to produce antibodies against components of the myelin sheath and may contribute to destruction of the myelin. 

How is Guillain-Barré syndrome diagnosed?

(provide clinical indicators of GBS)

Guillain-Barré is called a syndrome rather than a disease because it is not clear that a specific disease-causing agent is involved. A syndrome is a medical condition characterized by a collection of symptoms (what the patient feels) and signs (what a doctor can observe or measure).

Clinical Indicators of GBS:

• Major Indicator: Increased protein in the CSF with normal cell count (this is known as albuminocytologic dissociation)
  • This increased protein can lead to papilledema
• symptoms are generally symmetrical in GBS 
•  The quickness with which the symptoms appear is indicative of GBS over other neuro/muscular disorders 
• reflexes such as knee jerks are usually lost in GBS
• Nerve conduction velocity (NCV) test will show signals are traveling slower

A peripheral nerve disorder caused by diabetes or poor blood sugar control

(The most common types of diabetic neuropathy result in problems with sensation in the feet. It can develop slowly after many years of diabetes or may occur early in the disease. The symptoms are numbness, pain, or tingling in the feet or lower legs. The pain can be intense and require treatment to relieve the discomfort. The loss of sensation in the feet may also increase the possibility that foot injuries will go unnoticed and develop into ulcers or lesions that become infected.)

Is there any treatment to Diabetic Neuropathy?

The goal of treating diabetic neuropathy is to prevent further tissue damage and relieve discomfort.

• First, bring blood sugar levels under control by diet and medication.  
• Taking special care of the feet by wearing proper fitting shoes and routinely checking the feet for cuts and infections. 
• Analgesics, low doses of antidepressants, and some anticonvulsant medications may be prescribed for relief of pain, burning, or tingling. 
• (Some individuals find that walking regularly, taking warm baths, or using elastic stockings may help relieve leg pain.)                                     

Depends largely on how well the underlying condition of diabetes is handled.

• Treating diabetes may halt progression and improve symptoms of the neuropathy, but recovery is slow. 
• The painful sensations of diabetic neuropathy may become severe enough to cause depression in some patients.                                     

What is Vasculitis Syndromes of the Central and Peripheral Nervous Systems ?

Vasculitis is an inflammation of the vascular system, which includes the veins, arteries, and capillaries.  Researchers think that inflammation is due to a faulty immune system response. Vasculitis can cause problems in any organ system, including the central (CNS) and peripheral (PNS) nervous systems.  Vasculitis disorders, or syndromes, of the CNS and PNS are characterized by the presence of inflammatory cells in and around blood vessels, and secondary narrowing or blockage of the blood vessels that nourish the brain, spinal cord, or peripheral nerves.    

 Symptoms include:

• Headaches, especially a headache that doesn’t go away; 
• fever; 
•  rapid weight loss; 
• confusion or forgetfulness leading to dementia; 
• aches and pains in the joints and muscles; 
• pain while chewing or swallowing; 
• paralysis or numbness, usually in the arms or legs;
• visual disturbances, such as double vision, blurred vision, or blindness

Is there any treatment for CNS/PNS Vasculitis Syndrome?

Treatment for a vasculitis syndrome depends upon the specific diagnosis. 

• Most of the syndromes respond well to steroid drugs, such as prednisolone.  
• Some may also require treatment with an immunosuppressive drug, such as cyclophosphamide.