Laura Mayans, MD; David Mayans, MD Department of Family and Causes of peripheral neuropathy: Community Medicine (Dr. L. Mayans), Department of Internal Medicine (Dr. Diabetes and beyond D. Mayans), University of Kansas School of Medicine– Wichita; Neurology Leg paresthesias can be challenging to evaluate because Consultants of Kansas, Wichita (Dr. D. Mayans) of the varied causes and clinical presentations. This diagnostic guide with at-a-glance tables can help. [email protected] The authors reported no potential conflict of interest relevant to this article. CASE 1 u Sally G, age 46, has been experiencing paresthesias PRACTICE RECOMMENDATIONS for the past 3 months. She says that when she is cycling, the air on her legs feels much cooler than normal, with a similar feel- ❯ When evaluating a patient ing in her hands. Whenever her hands or legs are in cool water, with lower extremity numb- ness and tingling, order she says it feels as if she’s dipped them into an ice bucket. Sum- fasting blood glucose, vitamin mer heat makes her skin feel as if it's on fire, and she’s noticed B12 level with methylmalonic increased sweating on her lower legs. She complains of itching acid, and either serum protein (although she has no rash) and she’s had intermittent tingling electrophoresis (SPEP) or im- and burning in her toes. On neurologic exam, she demonstrates munofixation electrophoresis normal strength, sensation, reflexes, coordination, and cranial (IFE) because these test have nerve function. a high diagnostic yield. C ❯ Obtain SPEP or IFE when CASE 2 u Jessica T, age 25, comes in to see her family physician evaluating all patients because she’s been experiencing numbness in her right leg. It over age 60 with lower had begun with numbness of the right great toe about a year extremity paresthesias. C ago. Subsequently, the numbness extended up her foot to the ❯ Consider prescribing lateral aspect of the lower leg with an accompanying burning pregabalin for treating sensation. Three months prior to this visit, she developed weak- painful paresthesias because ness in her right foot and toes. She denies any symptoms in her strong evidence supports its left leg, upper extremities, or face. use; the evidence for A neurologic exam of the upper extremities is normal. gabapentin, sodium Ms. T also has normal cranial nerve function, and normal valproate, amitriptyline, strength, sensation, and reflexes in the left leg. A motor exam venlafaxine, and of the right leg reveals normal strength in the hip flexors, duloxetine is moderate. A hip adductors, hip abductors, and quadriceps. On the Medical Strength of recommendation (SOR) Research Council scale, she has 4/5 strength in the hamstrings, A Good-quality patient-oriented 0/5 in the ankle dorsiflexors, 1/5 in the posterior tibialis, and evidence 3/5 in the gastrocnemius. She has a normal right patellar re- B Inconsistent or limited-quality patient-oriented evidence flex, and an ankle jerk reflex and Babinski sign are absent. She C Consensus, usual practice, has reduced sensation on the posterior and lateral portions opinion, disease-oriented evidence, case series of the right leg and the entire foot. Sensation is preserved on the medial side of the right lower leg and anterior thigh. She has right-sided steppage gait. If these 2 women were your patients, how would you pro- ceed with their care? 774 THE JOURNAL OF FAMILY PRACTICE | DECEMBER 2015 | VOL 64, NO 12 Look for positive neuropathic symptoms such as cramping and tingling, negative symptoms such as numbness and weakness, and autonomic symptoms such as constipation, diarrhea, and sweating. aresthesias such as numbness and neuropathy, multiple mononeuropathy, or tingling in the lower extremities are polyneuropathy: Pcommon complaints in family medi- • Mononeuropathy is focal involve- cine. These symptoms can be challenging ment of a single nerve resulting from to evaluate because they have multiple po- a localized process such as compres- tential etiologies with varied clinical pre- sion or entrapment, as in carpal tunnel sentations.1 syndrome.1 A well-honed understanding of lower • Multiple mononeuropathy (mono- extremity anatomy and the location and neuritis multiplex) results from dam- characteristics of common complaints is age to multiple noncontiguous nerves essential to making an accurate diagnosis that can occur simultaneously or se- and treatment plan. This article discusses quentially, as in vasculitic causes of the tests to use when evaluating a patient neuropathy.1 who presents with lower extremity numb- • Polyneuropathy involves 2 or more ness and pain. It also describes the typical contiguous nerves, usually symmet- presentation and findings of several types ric and length-dependent, creating of peripheral neuropathy, and how to man- a “stocking-glove” pattern of pares- age them. thesias.1 Polyneuropathy affects lon- ger nerves first, and thus, patients will initially complain of symptoms Paresthesias are often the result in their feet and legs, and later their of peripheral neuropathy hands. Polyneuropathy is most com- IMAGE © JOE GORMAN While paresthesias can arise from disorders monly seen in diabetes. of the central or peripheral nervous system, Possible causes of peripheral neu- this article focuses on paresthesias that are ropathy include numerous anatomic, sys- the result of peripheral neuropathy. Periph- temic, metabolic, and toxic conditions eral neuropathy can be classified as mono- (TABLE 1).1,2 CONTINUED JFPONLINE.COM VOL 64, NO 12 | DECEMBER 2015 | THE JOURNAL OF FAMILY PRACTICE 775 TABLE 1 early satiety, constipation or diarrhea, im- Consider these causes potence, sweating abnormalities, and ortho- 3 1,2 stasis. The timing of onset, progression, and of peripheral neuropathy duration of such symptoms can give impor- Anatomic tant diagnostic clues. For example, an acute • Sciatica/sciatic compression onset of painful foot drop may indicate an in- flammatory cause such as vasculitis, whereas • Fibular nerve compression/entrapment slowly progressive numbness in both feet • Nerve dissection from surgery or accidental points toward a distal sensorimotor poly- injury neuropathy, likely from a metabolic cause. Systemic Symmetry or asymmetry at presentation, as • HIV infection well as speed of progression of symptoms, can also significantly narrow the differential • Carcinoma/paraneoplastic syndrome (TABLE 2). • Monoclonal gammopathy Determining the exact location of symp- • Amyloidosis toms is important and usually requires • Sarcoidosis prompting. For example, when a patient re- fers to “the legs,” he could mean anywhere • Sjögren’s syndrome from the foot to the hip. The presence of ra- An acute onset • Tick bite diating pain can also help localize the lesion, of painful Metabolic generally pointing to a radiculopathy (dis- foot drop may • Diabetes mellitus ease at the root of a nerve). Bowel or bladder involvement could suggest involvement of indicate an • Thyroid disease inflammatory the spinal cord or autonomic nervous system. cause of • Renal disease A thorough social history can help identi- neuropathic • Chronic liver disease fy potentially treatable causes of neuropathy. symptoms, such Toxic The probability of a toxic, infectious, or vita- min deficiency etiology can be ascertained by as vasculitis. • Vitamin deficiency (B1, B6, B12) inquiring about a patient’s occupation, sexu- • Vitamin B6 excess al history, dietary habits, and drug, alcohol, • Heavy metal poisoning (arsenic, lead, and tobacco history.3 Personal and family mercury) medical history can suggest possible genetic • Drug-induced (amiodarone, digoxin, or endocrine causes of neuropathy. A per- isoniazid, lithium, metronidazole, statins) sonal or family history of childhood “clumsi- • Organophosphate exposure ness” (suggestive of a hereditary neuropathy, such as Charcot-Marie-Tooth disease), dia- • Alcohol use betes mellitus, or thyroid, renal, hepatic, or HIV, human immunodeficiency virus. autoimmune diseases would be significant. A personal or family history of cancer is also an important diagnostic clue.3 What’s causing the neuropathy? The search for telltale clues While obtaining the history, ask the patient These tests help narrow about the presence of positive, negative, or the diagnostic possibilities autonomic neuropathic symptoms. Positive Motor and sensory testing are essential, as is symptoms, which usually present first, are testing of coordination and reflexes. Motor due to excess or inappropriate nerve activity examination involves manual muscle test- and include cramping, twitching, burning, ing. In many patients, pain can limit effort, and tingling.3 Negative symptoms are due to so encourage patients to try hard during test- reduced nerve activity and include numb- ing so you can determine the true severity of ness, weakness, decreased balance, and poor weakness. Sensory testing should include pin- sensation. Autonomic symptoms include prick, temperature differentiation, vibration, 776 THE JOURNAL OF FAMILY PRACTICE | DECEMBER 2015 | VOL 64, NO 12 PERIPHERAL NEUROPATHY TABLE 2 Getting to the root of peripheral neuropathy: Onset of symptoms and symmetry provide clues Acute Subacute Chronic Symmetric Guillain-Barré syndrome Monoclonal gammopathy Diabetes mellitus Organophosphate exposure Paraneoplastic syndromes Thyroid disease Paraneoplastic syndromes Liver or kidney disease Autoimmune disorders Inherited disorders Tick bite Vitamin B12 deficiency Autoimmune disorders Drug-induced CIDP (rare) Inherited disorders Asymmetric Tick bite Amyloidosis