Sensory & Peripheral

Neuropathies

Steve Sager, MPAS, PA-C

Learning Objectives

• List common neuropathies• List the common toxins which produce

neuropathies• Discuss the etiologies of common neuropathies• Differentiate between common neuropathies• Discuss the symptoms, signs, and treatments

– Diabetic neuropathies– Alcoholic neuropathies– Uremic neuropathies– Autonomic neuropathies

Harrison’s on Neuropathies

“The manifestations of such a disorder may be so bewildering and complex that it is difficult for a physician to know where to begin or how to proceed.”

General Information

• More than 100 types of peripheral neuropathy have been identified

• Each has its own characteristic set of symptoms, pattern of development, and prognosis

• May involve sensory, motor, and/or autonomic nerves

• A thorough patient history is critical

Common Neuropathies

• Trigeminal neuralgia (tic douloureux) • Postherpetic neuralgia• Carpal Tunnel Syndrome• Sciatica • Guillain-Barré syndrome• Peroneal Muscular Atrophy• Diabetic Neuropathy Syndromes• Alcoholic Neuropathy• Uremic Neuropathy

Etiology of Neuropathies

• Peripheral neuropathy may be– Inherited (C-M-T disease)– Acquired

• Diabetes mellitus is a leading cause of peripheral neuropathy in the United States– ~60-70% of people with diabetes have mild to

severe forms of nervous system damage.

• Neuropathies with no apparent cause are termed idiopathic

Etiology of Neuropathies

• Causes of acquired peripheral neuropathy include:– Physical injury (trauma) to a nerve– Tumors (neurofibromatoses) – Toxins

• Heavy metals• Medications

– Infections• Viral - HIV, EBV, HSV, CMV• Bacterial – Lyme disease

Etiology of Neuropathies

• Causes of acquired peripheral neuropathy include:– Kidney disease– Autoimmune disease– Nutritional deficiencies

• Vitamins E, B1, B6, B12, and niacin

– Alcoholism• Thiamine deficiency

– Vascular, metabolic, and endocrine disorders

Symptoms of Peripheral Neuropathies

• Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years– Muscle weakness is the most common

symptom of motor nerve damage– Sensory nerve damage causes a more

complex range of symptoms because sensory nerves have a wider, more highly specialized range of functions

Symptoms of Peripheral Neuropathies

• Sx’s of autonomic nerve damage are diverse and depend upon the affected organs/glands

• Autonomic nerve dysfunction can become life threatening and may require emergency medical care in cases when breathing becomes impaired or when the heart begins beating irregularly– Common symptoms of autonomic nerve damage

include:• unable to digest food easily • an inability to sweat normally, which may lead to heat

intolerance• a loss of bladder control, which may cause infection or

incontinence• an inability to control muscles that expand or contract blood

vessels to maintain safe blood pressure levels• organ failure may occur.

Symptoms of Peripheral Neuropathies

• Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged– Temporary numbness– Tingling/pricking sensations (paresthesia)– Sensitivity to touch– Burning pain (especially at night)– Muscle wasting– Paralysis– Organ or gland dysfunction

Symptoms of Peripheral Neuropathies

Fiber Type Negative phenomena

(loss of function)

Positive phenomena

(excessive firing)

Motor Weakness, atrophy, hypotonia, fatigability, clumsiness,

Twitching, cramps

Sensory Paresthesia, ataxia, clumsiness

“burning”, “tingling”,

“pins-and-needles” dysesthesia

Autonomic Orthostasis, anhidrosis, impotence, incontinence

Hyperhidrosis

Radiculopathies

• Cervical – due to stenosis or HNP– Sensory sx’s

• Neck, shoulder, or scapular pain increases with movement

– Motor sx’s• Loss of reflex based on nerve root involved

• Lumbosacral – onset after heavy lifting– Sensory sx’s

• Pain in lower back, hip or buttocks +/- radiation• Increases with prolonged sitting, coughing, sneezing or straining• HNP is generally unilateral• Spondylolysis/spondylolithesis typically presents with bilateral sx’s

– Motor sx’s• Loss of reflex

• Dx/Tx: X-rays, CT/MRI, NSAIDs, bed rest, traction

Toxic Neuropathies(ICD 357.7*)

• Organophosphates

• Toxins/Heavy metals– Lead– Arsenic

• Chronic uremia– Due to excessive levels of parathormone

• Medications (ICD 357.6*)– Antimetabolic/ChemoTx

Diabetic Polyneuropathies(ICD 357.2)

• Diabetes affects ~6% of the population• Vascular and neurological complications

are the most common causes of morbidity & mortality

• Neuropathy affects 25-50%– Directly related to the length of time that nerve

fibers are exposed to hyperglycemia– Mixed polyneuropathy– Usually affects motor, sensory & autonomic

Diabetic Neuropathy Syndromes

• Glucose becomes incorporated into proteins– AGEs are formed (irreversible)– Reactive oxidants are produced– Cause damage to collagen structure,

basement membrane thickening, increased inflammatory responses and vascular permeability

Diabetic Neuropathy Syndromes

• Two types:– Peripheral

• Focal– Mononeuropathy affecting PNS or CNs

• Generalized– Symmetric, peripheral, sensory polyneuropathy– Insidious and progressive

– Autonomic• May result in erectile dysfunction, gastropathy, or

hypoglycemia• Cardiovascular complications

– Orthostatic hypotension– Myocardial infarction– Malignant arrhythmia– Sudden death

Diabetic Neuropathy Syndromes

• Focal or multifocal• Occur secondary to vasculitis/ischemia• Acute onset of pain

– Resolves spontaneously <6 weeks

• May involve:– CN III, IV, VI, VII– Ulnar or median nerve– Peroneal, sural, sciatic, or femoral nerve– Amyotrophy of proximal thigh muscles– Diabetic truncal radiculoneuropathy

Diabetic Neuropathy Syndromes

• Can be detected during a routine exam• Inspect feet for deformities and sensory loss

– Loss of ankle reflexes– Loss of Hot/Cold sensation– Loss of vibratory sense

• 128Hz tuning fork to hallux

– Monofilament test• Use 10 gauge monofilament

– Charcot foot = xerosis, venous distension, multiple

bony deformities

• EMG and NCS confirm the diagnosis

Monofilament Test• There is a risk of ulcer

formation if the patient is unable to feel the monofilament when it is pressed against the foot with just enough pressure to bend the filament

• The patient is asked to say "yes" each time he or she feels the filament

• Failure to feel the filament at four of 10 sites is 97 percent sensitive and 83 percent specific for identifying loss of protective sensation

Diabetic Mononeuropathies

• CN III or CN VI are commonly affected– NOT associated with pupillary abnormalities

• CTS (median neuropathy)– Occurs in ~6% of diabetics– Acute onset of painful paresthesias in fingers

with radiating “ache” to forearm• Worse HS• Motor weakness is progressive with thenar wasting• Positive Phalen test and/or Tinel sign

Diabetic Autonomic Neuropathy

• GI-related:– Characterized by gastroparesis, nausea/emesis

and diarrhea– Improve overall glycemic control**– +/- improvement of GI sx’s with Metoclopramide– Tx diarrhea with Clonidine QD (+/- TCN)

• GU-related:– Characterized by impotence, impaired

sensation to voiding, and retrograde ejaculation

Treatment ofDiabetic Neuropathy Syndromes

• Improved metabolic control is the main goal of treatment– Control lipids– Manage HTN (ACE inhibitors)– Lifestyle intervention

• Intensive insulin therapy– 3-4 injections QD or an insulin pump reduced

electrophysiologic evidence by up to 64%

• ASA• Magnesium oxide 250-750mg HS

Treatment ofDiabetic Neuropathy Syndromes

• Analgesics– Tramadol

• Neuromodulators– Gabapentin

• Carbamazepine (Tegretol)• Capsaicin

– Tx neuropathic pain: rub in for 5 minutes BID

• TCAs• Daily foot exam by patient!!!

– Use mirrors

• Annual PCP examination is required

Diabetic Autonomic Neuropathy

• Avoid medications that can cause syncope:– Alpha-blockers, anti-HTN, antidepressants

• Frequent accuchecks

• Maintain adequate hydration

• Minimize cardiac-related AN:– Monitor for orthostatic hypotension

• Increased risk of sudden death/silent ischemia

– Improve mgmt of glucose, lipids, and HTN – Use ACE inhibitors*

Diabetic Neuropathy Syndromes

• Foot ulceration and amputation are the most common consequences

• Risk factors for amputation:– Poor glycemic control– Alcohol abuse– Obesity– Loss of protective sensation– Altered biomechanics/foot deformities– Diagnosis >10 years– Gender– Peripheral vascular disease

Neuropathy Disability Score

Sensation Score

Vibration Apply 128-Hz tuning fork to apex of great toe

Normal = can distinguish presence/absence of vibration

Abnormal

0

1

Temperature Apply temperature variants to dorsum of foot

Normal = can distinguish temperature variants

Abnormal

0

1

Pinprick Apply pin proximal to great toenail

Normal = can distinguish sharpness

Abnormal

0

1

Achilles reflex Present

Present with reinforcement

Absent

0

1

2

Total for one foot 0-5

A total score (for both feet) of 6 or greater is predictive of foot ulceration.

Alcoholic Polyneuropathy(ICD 357.5)

• Establish Dx of alcohol abuse– Preoccupation– Increased tolerance– Drinking alone– Use as a “medication”– Blackouts– Physical/Social/Family issue

• CAGE questionnaire• ? Vitamin deficiency

Alcoholic Polyneuropathy

• Wernicke-Korsakoff syndrome– CNS injury related to thiamine deficiency– Nystagmus, ataxia, confusion, EOM paralysis

• Peripheral polyneuropathy– Earliest symptom of chronic alcoholism– Mostly sensory with +/- motor involvement– “Burning” sensation in feet

• Dementia – due to cerebral atrophy• Cerebellar degeneration – truncal ataxia• Myopathy – proximal muscle wasting• Hepatic encephalopathy

– Altered consciousness/lethargy– Ataxia/dysarthria/asterixis

Alcoholic Polyneuropathy

• Delirium Tremens (DTs)– Alcohol withdrawal syndrome– Occurs 72-96 hours after cessation– Often fatal– Similar to withdrawal from barbiturates/benzos– Mild tremors seizures– “Jittery” and easily startled– Hallucinations– Autonomic hyperactivity

Alcoholic Polyneuropathy

• Seizures are common– Generalized (“Rum fits”)

• Occur 12-48 hours after decreased ETOH intake

– Focal • Occur during periods of intoxication

• Tx:– Supportive (diet, vitamins, etc.)– Librium – Diazepam– Thiamine (50mg IV and 50mg IM QD)

Uremic Neuropathy (Uremia)(ICD 357.4)

• Presents with altered mental status– Variable– Irritability– Difficulty concentrating– Psychosis

• May have convulsions– Secondary to acidosis, hypokalemia, hyponatremia

• Often occurs postdialysis/postdiuresis• Most patients with BUN>60 have EEG changes• R/O infection and subdural hematoma

Uremic Neuropathy

• Additional (late) symptoms:– Peripheral neuropathy– “Restless leg syndrome”– “Burning” paresthesias of the feet– Sensory loss in digits– Asterixis– Fasciculations– Myoclonus– Muscle cramps– Amaurosis– Cerebral emboli– Dementia

Autonomic Neuropathies

• Parasympathetic neuropathies typically involve the cranial nerves or sacral nerves

• Sympathetic neuropathies involve the medulla oblongata, spinal cord, or sympathetic ganglia

• Both involve receptors in the smooth muscles and glands

Clinical Manifestations of Autonomic Neuropathies

• Sudden death• Tremors• Hyperthermia• Altered sweating• Tachycardia• Orthostatic hypotension• Syncope• Gastroparesis• GU dysfunction

Conditions Associated with Autonomic Neuropathies

• Poisoning– Atropine– Anticholinesterase inhibitors

• Horner’s syndrome– Oculosympathetic paralysis

• Ptosis• Miosis• Anhidrosis

• Shy-Dragger syndrome– Progressive autonomic failure– Multiple system atrophy– Progressive and fatal

Conditions Associated with Autonomic Neuropathies

• Pheochromocytoma– Tumors arising from chromaffin cells in the

sympathetic nervous system– Release Epinephrine and NE into circulation– Cause autonomic hyperactivity

• Paroxysmal hypertension• Diaphoresis• Flushing• Tachycardia• Anxiety

– Test blood/urine for catecholamines, metanephrines and vanillylmandelic acid (VMA)

Assessment of PossibleAutonomic Neuropathies

• Orthostatic VS

• ECG– Look for R-R variability

• Tilt test

• Cold pressor test

• Sweat provocation

Treatment of Neuropathies

• Several classes of drugs have recently proved helpful to many patients suffering from more severe forms of chronic neuropathic pain– Antiepileptic drugs

• Phenytoin (Dilantin)• Carbamazepine (Tegretol)

– Some classes of antidepressants (Tricyclics)– Gabapentin (Neurontin)– Mexiletine (Mexitil)

• developed to correct irregular heart rhythms• sometimes associated with severe side effects

Treatment of Neuropathies

• Neuropathic pain is often difficult to control– Use smallest effective dose and titrate– Mild pain may sometimes be alleviated by OTC

analgesics– Limit narcotic use– Corticosteroids may help reduce inflammation

• Injections of local anesthetics such as lidocaine or topical patches containing lidocaine may relieve more intractable pain

• In the most severe cases, doctors can surgically destroy nerves– The results are often temporary and the procedure

can lead to complications.

Information Resources• Neuropathy Association

60 East 42nd StreetSuite 942New York, NY   10165-0999http://www.neuropathy.orgTel: 212-692-0662 800-247-6968Fax: 212-692-0668

• National Chronic Pain Outreach Association (NCPOA)P.O. Box 274Millboro, VA   24460http://www.chronicpain.orgTel: 540-862-9437Fax: 540-862-9485

• American Chronic Pain Association (ACPA)P.O. Box 850Rocklin, CA   95677-0850http://www.theacpa.orgTel: 916-632-0922 800-533-3231Fax: 916-632-3208

Information Resources• Charcot-Marie-Tooth Association (CMTA)

2700 Chestnut ParkwayChester, PA   19013-4867http://www.charcot-marie-tooth.orgTel: 610-499-9264 800-606-CMTA (2682)Fax: 610-499-7267

• American Pain Foundation201 North Charles StreetSuite 710Baltimore, MD   21201-4111http://www.painfoundation.orgTel: 888-615-PAIN (7246) 410-783-7292Fax: 410-385-1832

• National Foundation for the Treatment of PainP.O. Box 70045Houston, TX   77270http://www.paincare.orgTel: 713-862-9332Fax: 713-862-9346

Summary

• List common neuropathies• Etiologies of common neuropathies• Differentiate between common neuropathies• Discuss treatment options for common neuropathies• List the common toxins which produce neuropathies• Symptoms, signs, and treatments of

– Guillain-Barré syndrome– Peroneal Muscular Atrophy– Diabetic neuropathies– Alcoholic neuropathies– Uremic neuropathies– Autonomic neuropathies

Summary

• Diabetes mellitus is a leading cause of peripheral neuropathy in the United States

• Diabetic Neuropathy Syndromes– Vascular and neurological complications are the most

common causes of morbidity & mortality– Foot ulceration and amputation are the most common

consequences– CTS (median neuropathy) occurs in ~6%– Improved metabolic control is the main goal of

treatment– Daily foot exam by patient is essential

Summary

• Alcoholic Neuropathy– Peripheral polyneuropathy is the earliest

symptom of chronic alcoholism – Wernicke-Korsakoff syndrome results from

CNS injury related to thiamine deficiency– Seizures are common

• Uremic Neuropathy– Presents with altered mental status– Often occurs postdialysis/postdiuresis

Summary

• Autonomic neuropathies affect receptors in the smooth muscles and glands

• Clinical manifestations of autonomic neuropathies include sudden death, hyperthermia, altered sweating, orthostatic hypotension, and gastroparesis

• Neuropathic pain is difficult to control