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Peripheral Neuropathiesin Older Adults
Annabel K. Wang, MDUniversity 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
• Motor neuron disorders
• Radiculopathies
• Plexopathies
• Single and Multiple Mononeuropathies
• Symmetric Polyneuropathies
• Motor Neuropathies
• Sensory Ganglionopathies
Objectives
• Review symptoms and signs
• Identify common causes
• Discuss treatment options
• Address co-morbidities
Symptoms
• Positive or negative phenomena
• Sensory symptoms early
• Typically symmetric in onset
• Weakness later
• Distal symptoms predominant
• Worse at night
Positive Phenomena
• Tingling
• Coldness
• Burning
• Electrical shocks
• Stabbing sensations
• Deep aching
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
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
• 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”
Metabolic Causes
• Diabetes
• Uremia
• Alcohol abuse
• Hypothyroid
• Vitamin B1 or B12 deficiency
• Vitamin B6 toxicity
• Medications/chemotherapy
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
Autonomic Symptoms
• Lightheadedness or “dizziness”• Blurred vision• Dry eyes, dry mouth• Cold feet• Early satiety, constipation, diarrhea• Urinary retention, incontinence• Erectile Dysfunction• Hypohidrosis
Dysautonomias• Diabetes• Amyloidosis (acquired and inherited)• Paraneoplastic• Inherited (HSAN)• Sjogren’s Neuropathy• Porphyria
Differential Diagnosis
• Small fiber neuropathy
• Plantar fasciitis
• Osteoarthritis
• Vascular insufficiency
• Cervical myelopathy
• Lumbosacral radiculopathy
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
• 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
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.
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
• 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
• Depression
• Decreased mobility
• Falls
• Fear of falls
• Social isolation
• Osteoporosis
Complications
• 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
References• Diabetes Statistics.
http://www.diabetes.org/diabetes-basics/diabetes-statistics/• 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/1165419-overview#aw2aab6b6
• Rutkove SB. Overview of polyneuropathy. http://www.uptodate.com/contents/overview-of-polyneuropathyUpto date