Annabel K. Wang, MD
University of California, Irvine
Department of Neurology

• Common disorder
• Prevalence of non-traumatic peripheral neuropathies
• 2.4% in general population
•
15% over the age of 40

•
Terms are confusing
– polyneuropathy
– neuropathy

• Motor neuron disorders
•
Radiculopathies
•
Plexopathies
•
Single and Multiple Mononeuropathies
•
Symmetric Polyneuropathies
•
Motor Neuropathies
•
Sensory Ganglionopathies

•
Early Recognition
•
Early Treatment
•
Prevention of Complications

•
Review symptoms and signs
•
Identify common causes
•
Discuss treatment options
•
Address co-morbidities

•
Positive or negative phenomena
•
Sensory symptoms early
•
Typically symmetric in onset
•
Weakness later
•
Distal symptoms predominant
•
Worse at night

•
Tingling
•
Coldness
•
Burning
•
Electrical shocks
•
Stabbing sensations
•
Deep aching

•
Lack of sensation
•
Hypersensitivity

•
Imbalance
•
Fatigue
•
Falls

• Distal sensory loss:
• Large Fibers
• loss of vibration before proprioception
• decreased ankle reflexes
• Small fibers
• Loss of pinprick and temperature
• Stocking-glove distribution

•
Distal weakness
–
Toe extensors
–
Foot dorsiflexors
–
Finger extensors

•
Diabetes
•
Leprosy
•
Vitamin B12 deficiency

•
Prevalence of Diabetes (2011): 8.3% of population
•
25.8 million children and adults in the US
•
Age 65 years or older
–
10.9 million, or 26.9% of this age group have diabetes

•
60-70% will develop neuropathy
– polyneuropathy, autonomic neuropathy, CTS
•
Association with amputation
– major contributor of amputations
–
60% of non-traumatic amputations
–
65,700 amputations from 2006

•
Defined as the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes
•
An absence of symptoms should never be assumed to indicate an absence of signs

•
Treatment
–
Glucose control
–
Pain management
–
Management of autonomic symptoms

•
Rare in United States
•
Endemic areas
•
Often sensory (ulnar and peroneal nerves)
•
Associated skin lesions
•
Hypertrophic nerves
•
Nerve biopsy
•
Treat underlying infection

•
Prevalence: 5-20%
•
Malabsorption, insufficient intake, pernicious anemia, gastric bypass surgery, medications
•
Distal sensory and motor loss
•
Combined subacute degeneration
•
Vitamin B12 (<260 pmol/L) and methylmalonic acid (271 nmol/L) levels
•
Supplementation: intramuscular or oral

•
Acute vs. chronic onset
–
Acute fulminant and live threatening
•
Axonal vs. demyelinating
–
Demyelinating forms respond well to immunotherapy

•
Guillain-Barre Syndrome or Acute
Inflammatory Demyelinating
Polyradiculoneuropathy
•
Porphyria
•
Toxic (arsenic and thallium)

•
Inherited (CMT, HMSN, HNPP)
–
Family History
–
Foot Deformities
–
Foot Ulcers
•
Acquired
– “MINI”

“MINI”
•
Metabolic
•
Immune
•
Neoplastic
•
Infectious

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Diabetes
•
Uremia
•
Alcohol abuse
•
Hypothyroid
•
Vitamin B1 or B12 deficiency
•
Vitamin B6 toxicity
•
Medications/chemotherapy

•
Vasculitis
•
Non-vasculitic
–
CIDP
–
MMN
–
Sarcoid
– Sjogren’s

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Paraneoplastic
•
Paraproteinemic

•
M onoclonal g ammopathy of u nclear s ignificance
•
Prevalence:
–
3% of persons >50 years
–
5% >70 years
•
1% per year risk of progression to multiple myeloma
(MM) or a related disorder

•
Leprosy
•
Hepatitis C
•
Lyme
•
HIV
•
West Nile
•
Syphilis
•
Diptheria

• Lightheadedness or “dizziness”
•
Blurred vision
• Dry eyes, dry mouth
•
Cold feet
• Early satiety, constipation, diarrhea
•
Urinary retention, incontinence
• Erectile Dysfunction
•
Hypohidrosis

•
Diabetes
•
Amyloidosis (acquired and inherited)
•
Paraneoplastic
•
Inherited (HSAN)
• Sjogren’s Neuropathy
•
Porphyria

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Small fiber neuropathy
•
Plantar fasciitis
•
Osteoarthritis
•
Vascular insufficiency
•
Cervical myelopathy
•
Lumbosacral radiculopathy

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Electromyography
•
Autonomic Testing
•
Quantitative Sensory Studies

• Two part test:
•
Nerve conduction studies
•
Needle electromyography
•
Establish diagnosis of polyneuropathy
• Distinguish demyelinating from axonal
•
Differentiate radiculopathy, plexopathy
•
Normal in small fiber and autonomic neuropathy

•
Heart rate response to deep breathing
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Valsalva Maneuver
•
Tilt Table
•
Quantitative Sudomotor Axon Reflex Test

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Hematology :
– complete blood count
– erythrocyte sedimentation rate
–
C-reactive protein
– vitamin B12, folate,
–
Methylmalonic acid, homocysteine

•
Biochemical and endocrine :
– comprehensive metabolic panel (fasting glucose)
– thyroid function tests
– serum immunofixation.
– glucose tolerance test if indicated

•
Urine:
– urinalysis
– urine immunofixation.
•
Drugs and toxins

Specialized Laboratory Investigation
•
Malignancies:
– skeletal radiographic survey
– mammography
– computed tomography or magnetic resonance imaging of chest, abdomen, and pelvis
– ultrasound of abdomen and pelvis
– positron emission tomography
– cerebrospinal fluid analysis including cytology
– serum paraneoplastic antibody profile

Specialized Laboratory Investigation
•
Connective tissue diseases and vasculitis :
– antinuclear antigen profile
– rheumatoid factor
– anti-Ro/SSA, anti-La/SSB,
– antineutrophil cytoplasmic antigen antibody
(ANCA) profile
– cryoglobulins.

Specialized Laboratory Investigation
•
Infectious agents:
–
Campylobacter jejuni
–
Cytomegalovirus
– hepatitis panel (B and C)
–
HIV
–
Lyme disease
– herpes viruses
–
West Nile virus
– cerebrospinal fluid analysis.

•
Nerve biopsy
•
Sural
•
Superficial peroneal
•
Epidermal skin biopsy

•
Vasculitis
•
Lymphoma
•
Amyloid
•
Sarcoid
•
Leprosy
•
Inflammation


Care of feet
• Inspect feet daily (mirror)
• Keep feet clean and moisturized
• Foot care with podiatrist
• Molded shoes
• Avoid walking barefoot
• Checking temperatures of water/sand

•
Foot care
•
Physical Therapy
•
Gait and balance exercises
•
Ankle supports (orthotics)
•
Occupational Therapy (ADLs)

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Importance of diagnosis
•
Recognition of the underlying cause
•
Glucose control
•
Thyroid medication
•
Vitamin supplementation or reduction
•
Antibiotics or antiviral medications
•
Immunotherapy

•
Only 2 medications are FDA approved for diabetic polyneuropathy
–
Duloxetine
– pregabalin

•
Pain management limited by side effects
–
Analgesics
–
Anti-inflammatories
–
Antiepileptics
–
Antidepressants
–
Narcotics

•
Depression
•
Decreased mobility
•
Falls
•
Fear of falls
•
Social isolation
•
Osteoporosis

• Risk of injury due to lack of sensation
• Charcot joints
• Foot ulcers
• Amputations
• Falls

•
Common disorder
–
>40 years of age: 15%
•
Routine screening for diabetes, vitamin B12 deficiency, serum immunofixation.

•
Neurophysiological tests distinguish axonal
/demyelinating/autonomic/small fiber
•
Demyelinating neuropathies are commonly inflammatory and treatable.
•
Axonal neuropathies have multiple causes

•
Treatment
–
Therapeutic
–
Symptomatic
–
Comorbidities

•
Diabetes Statistics. http://www.diabetes.org/diabetes-basics/diabetesstatistics/
•
Bril V et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology; Published online before print April 11, 2011; DOI
10.1212/WNL.0b013e3182166ebe
•
Bril V. Treatments for diabetic neuropathy. JPNS 2012:17(s2);22–27.
•
Leishear K et al. Relationship Between Vitamin B12 and Sensory and
Motor Peripheral Nerve Function in Older Adults. JAGS 2012:60(6);
1057–1063.
•
England JD et al. Evaluation of distal symmetric polyneuropathy: the role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Muscle Nerve 2009 ;39: 106–115.
• England JD et al. Evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review). Muscle Nerve
2009 ;39: 116–125.

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Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression. BJH 2007:139(5);730–743.
•
Mauermann ML, Burns TM. The evaluation of chronic axonal polyneuropathies. Semin Neurol. 2008:28(2):133-51.
•
Ramaratnam S. Neurologic Manifestations of
Leprosy. http://emedicine.medscape.com/article/1165419overview#aw2aab6b6
•
Rutkove SB. Overview of polyneuropathy.
http://www.uptodate.com/contents/overview-of-polyneuropathyUpto date