Transcript Presentation - University of California, Irvine

Peripheral Neuropathies
in Older Adults
Annabel K. Wang, MD
University of California, Irvine
Department of Neurology
Peripheral Neuropathies
• Common disorder
• Prevalence of non-traumatic peripheral
neuropathies
• 2.4% in general population
• 15% over the age of 40
Peripheral Neuropathies
• Terms are confusing
– polyneuropathy
– neuropathy
Peripheral Neuropathies
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Motor neuron disorders
Radiculopathies
Plexopathies
Single and Multiple Mononeuropathies
Symmetric Polyneuropathies
Motor Neuropathies
Sensory Ganglionopathies
Goals
• Early Recognition
• Early Treatment
• Prevention of Complications
Objectives
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Review symptoms and signs
Identify common causes
Discuss treatment options
Address co-morbidities
Symptoms
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Positive or negative phenomena
Sensory symptoms early
Typically symmetric in onset
Weakness later
Distal symptoms predominant
Worse at night
Positive Phenomena
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Tingling
Coldness
Burning
Electrical shocks
Stabbing sensations
Deep aching
Negative phenomena
• Lack of sensation
• Hypersensitivity
Associated Symptoms
• Imbalance
• Fatigue
• Falls
Early Signs
• Distal sensory loss:
• Large Fibers
• loss of vibration before proprioception
• decreased ankle reflexes
• Small fibers
• Loss of pinprick and temperature
• Stocking-glove distribution
Early Signs
• Distal weakness
– Toe extensors
– Foot dorsiflexors
– Finger extensors
Common Causes
• Diabetes
• Leprosy
• Vitamin B12 deficiency
Diabetes
• 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
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
Diabetic Polyneuropathy
• 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
Diabetic Polyneuropathy
• Treatment
– Glucose control
– Pain management
– Management of autonomic symptoms
Leprosy
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Rare in United States
Endemic areas
Often sensory (ulnar and peroneal nerves)
Associated skin lesions
Hypertrophic nerves
Nerve biopsy
Treat underlying infection
Vitamin B12 Deficiency
• 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
Approach
• Acute vs. chronic onset
– Acute fulminant and live threatening
• Axonal vs. demyelinating
– Demyelinating forms respond well to
immunotherapy
Acute Polyneuropathies
• Guillain-Barre Syndrome or Acute
Inflammatory Demyelinating
Polyradiculoneuropathy
• Porphyria
• Toxic (arsenic and thallium)
Chronic Polyneuropathies
• Inherited (CMT, HMSN, HNPP)
– Family History
– Foot Deformities
– Foot Ulcers
• Acquired
– “MINI”
Acquired Polyneuropathy
“MINI”
• Metabolic
• Immune
• Neoplastic
• Infectious
Metabolic Causes
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Diabetes
Uremia
Alcohol abuse
Hypothyroid
Vitamin B1 or B12 deficiency
Vitamin B6 toxicity
Medications/chemotherapy
Immune Causes
• Vasculitis
• Non-vasculitic
– CIDP
– MMN
– Sarcoid
– Sjogren’s
Neoplastic Causes
• Paraneoplastic
• Paraproteinemic
MGUS
• Monoclonal gammopathy of unclear significance
• Prevalence:
– 3% of persons >50 years
– 5% >70 years
• 1% per year risk of progression to multiple myeloma
(MM) or a related disorder
Infectious Causes
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Leprosy
Hepatitis C
Lyme
HIV
West Nile
Syphilis
Diptheria
Autonomic Symptoms
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Lightheadedness or “dizziness”
Blurred vision
Dry eyes, dry mouth
Cold feet
Early satiety, constipation, diarrhea
Urinary retention, incontinence
Erectile Dysfunction
Hypohidrosis
Dysautonomias
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Diabetes
Amyloidosis (acquired and inherited)
Paraneoplastic
Inherited (HSAN)
Sjogren’s Neuropathy
Porphyria
Differential Diagnosis
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Small fiber neuropathy
Plantar fasciitis
Osteoarthritis
Vascular insufficiency
Cervical myelopathy
Lumbosacral radiculopathy
Neurophysiology
• Electromyography
• Autonomic Testing
• Quantitative Sensory Studies
Electromyography (EMG)
• 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
Autonomic Testing
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Heart rate response to deep breathing
Valsalva Maneuver
Tilt Table
Quantitative Sudomotor Axon Reflex Test
Basic Laboratory Investigation
• Hematology:
– complete blood count
– erythrocyte sedimentation rate
– C-reactive protein
– vitamin B12, folate,
– Methylmalonic acid, homocysteine
Basic Laboratory Investigation
• Biochemical and endocrine:
– comprehensive metabolic panel (fasting glucose)
– thyroid function tests
– serum immunofixation.
– glucose tolerance test if indicated
Basic Laboratory Investigation
• 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.
Biopsy
• Nerve biopsy
• Sural
• Superficial peroneal
• Epidermal skin biopsy
Nerve Biopsy
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Vasculitis
Lymphoma
Amyloid
Sarcoid
Leprosy
Inflammation
Management
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
Treatment
• Foot care
• Physical Therapy
• Gait and balance exercises
• Ankle supports (orthotics)
• Occupational Therapy (ADLs)
Therapeutic Treatment
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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
Symptomatic Treatment
• Only 2 medications are FDA approved for
diabetic polyneuropathy
– Duloxetine
– pregabalin
Symptomatic Treatment
• Pain management limited by side effects
– Analgesics
– Anti-inflammatories
– Antiepileptics
– Antidepressants
– Narcotics
Co-morbidities
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Depression
Decreased mobility
Falls
Fear of falls
Social isolation
Osteoporosis
Complications
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Risk of injury due to lack of sensation
Charcot joints
Foot ulcers
Amputations
Falls
Summary
• Common disorder
– >40 years of age: 15%
• Routine screening for diabetes, vitamin B12
deficiency, serum immunofixation.
Summary
• Neurophysiological tests distinguish axonal
/demyelinating/autonomic/small fiber
• Demyelinating neuropathies are commonly
inflammatory and treatable.
• Axonal neuropathies have multiple causes
Summary
• Treatment
– Therapeutic
– Symptomatic
– Comorbidities
References
• 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.
References
• 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