ORIGINAL CONTRIBUTION Chronic Cryptogenic Sensory Polyneuropathy Clinical and Laboratory Characteristics Gil I. Wolfe, MD; Noel S. Baker, MD; Anthony A. Amato, MD; Carlayne E. Jackson, MD; Sharon P. Nations, MD; David S. Saperstein, MD; Choon H. Cha, MD; Jonathan S. Katz, MD; Wilson W. Bryan, MD; Richard J. Barohn, MD Background: Chronic sensory-predominant polyneu- duration of symptoms of 62.9 months. Symptoms al- ropathy (PN) is a common clinical problem confronting most always started in the feet and included distal numb- neurologists. Even with modern diagnostic approaches, ness or tingling in 86% of patients and pain in 72% of many of these PNs remain unclassified. patients. Despite the absence of motor symptoms at pre- sentation, results of motor nerve conduction studies were Objective: To better define the clinical and laboratory abnormal in 60% of patients, and electromyographic evi- characteristics of a large group of patients with crypto- dence of denervation was observed in 70% of patients. genic sensory polyneuropathy (CSPN) evaluated in 2 uni- Results of laboratory studies were consistent with axo- versity-based neuromuscular clinics. nal degeneration. Patients with and without pain were similar regarding physical findings and laboratory test ab- Design: Medical record review of patients evaluated normalities. Only a few patients (,5%) had no evi- for PN during a 2-year period. We defined CSPN on dence of large-fiber dysfunction on physical examina- the basis of pain, numbness, and tingling in the distal tion or electrophysiologic studies. All 66 patients who extremities without symptoms of weakness. Sensory had follow-up examinations (mean, 12.5 months) re- symptoms and signs had to evolve for at least 3 mained ambulatory. months in a roughly symmetrical pattern. Identifiable causes of PN were excluded by history, physical Conclusions: Cryptogenic sensory polyneuropathy is a examination findings, and results of laboratory stud- common, slowly progressive neuropathy that begins in ies. We analyzed clinical and laboratory data from late adulthood and causes limited motor impairment. Iso- patients with CSPN and compared findings in patients lated small-fiber involvement is uncommon in this group with and without pain. of patients. Management should focus on rational phar- macotherapy of neuropathic pain combined with reas- Results: Of 402 patients with PN, 93 (23.1%) had CSPN surance of CSPN’s benign clinical course. and stable to slowly progressive PN syndrome. These pa- tients presented with a mean age of 63.2 years and a mean Arch Neurol. 1999;56:540-547 CQUIRED chronic sensory- reditary neuropathies,8 recognition of im- predominant polyneu- mune-mediated neuropathies,9 causes ropathies (PNs) are com- becoming apparent over time,3 and the de- mon in middle and late velopment of more sophisticated diagnos- adulthood, with an esti- tic approaches. Amated prevalence of more than 3%.1 Most There are few detailed reports of elec- are secondary to readily identifiable causes, trophysiologic findings in the literature, such as diabetes. However, once known but available data suggest that most idio- causes are excluded, a sizable minority re- pathic PN is axonal.5,9 There is less con- main idiopathic. The cryptogenic group sensus on the clinical course for this group was thought to compose as much as 50% of patients. In 1 report,5 most patients (81%) were unchanged or improved af- ter median follow-up of 3 years. Another From the Departments of For editorial comment study10 reported some progression in all Neurology, University of Texas see page 519 71 patients followed up for 4 to 7 years. Southwestern Medical Center, Dallas (Drs Wolfe, Baker, to 70% of PN cases in early series2,3 and Nations, Saperstein, Cha, Katz, 4 5-8 Bryan, and Barohn), and even in 1 recent report. Recent studies have revised this number down to 10% to This article is also available on our University of Texas Health Web site: www.ama-assn.org/neuro. Sciences Center, San Antonio 35%. Likely reasons for the declining per- (Drs Amato and Jackson). centage include better recognition of he- ARCH NEUROL / VOL 56, MAY 1999 540 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 PATIENTS AND METHODS virus or other infections, pertinent toxic or pharmacological exposures, hereditary neuropathy or amyloidosis, and pri- mary amyloidosis were excluded by history and laboratory Medical records were reviewed on all patients evaluated for testing. PN during a 2-year period in our university-based neuro- Nearly all patients underwent routine nerve conduc- muscular clinics. We defined patients with CSPN on the tion studies (NCSs) and needle electromyography (EMG). basis of pain, numbness, or tingling in the distal extremi- Laboratory reference values used for the NCSs are listed ties without symptoms of weakness. Sensory symptoms had in Table 1. Thirty-nine patients underwent QST per- to occur in a roughly symmetrical pattern in the distal lower formed with the Computer-Assisted Sensory Examination extremities or upper extremities or both and evolve for at system (CASE IV; WR Medical Electronics, Stillwater, Minn) least 3 months. On neurologic examination, patients had using a 4, 2, and 1 stepping protocol.11 Fewer patients un- to demonstrate distal sensory deficits to either light touch, derwent QST than NCSs and EMG because routine appli- vibration, position, or pinprick that were not confined to cation of QST was established in only 1 of our laboratories the distribution of an individual peripheral nerve. Slight during the study. The CASE IV system is equipped with distal weakness in foot or hand intrinsic muscles was per- age-matched control values for vibration and cooling sen- mitted as long as motor symptoms were not a presenting sory thresholds. Vibration and cooling thresholds equal to complaint. or greater than the 95th percentile were considered abnor- Routine laboratory tests consisted of a complete chem- mal.12,13 Serum testing for antisulfatide antibodies (Athena istry battery and blood cell count, erythrocyte sedimenta- Diagnostics, Worcester, Mass) was performed in 41 pa- tion rate, antinuclear antibodies, rheumatoid factor, vita- tients, and sural nerve biopsies were performed in 14 pa- min B12 level, thyroid function tests, syphilis serologic tients. screening, and serum protein electrophoresis with immuno- Clinical and laboratory data in patients with pain were fixation electrophoresis. Patients with monoclonal proteins compared with results in the smaller group of patients who were included in the study population only if plasma cell dys- did not report pain. x2 Contingency table analysis with the crasias were ruled out after evaluation by an oncologist and Yates correction factor was used for most comparisons. a diagnosis of monoclonal gammopathy of uncertain signifi- When appropriate, the Fisher exact test or Student t test cance (MGUS). Patients were excluded if they had signifi- was substituted. cant abnormal findings on the other laboratory studies. Pa- Symptomatic therapy for painful sensory symptoms tients with identifiable causes of neuropathy such as diabetes, was attempted using a variety of standard pharmacologi- chronic alcohol use, metabolic disturbances, endocrine ab- cal agents. A favorable clinical response was considered pres- normalities, connective tissue diseases including sicca ent if patients reported a significant decrease in or resolu- complex, malignant neoplasms, human immunodeficiency tion of their symptoms. This study’s intent was to better define the clinical and tremor were uncommon presentations, accounting and laboratory characteristics of a large group of pa- for only 4 patients. In all, 67 patients presented with tients with chronic cryptogenic sensory polyneuropa- pain and 26 patients presented without pain. Symptoms thy (CSPN) evaluated in 2 university-based neuromus- were confined to the distal lower extremities in 41 cular clinics. In addition to routine electrophysiologic patients (44%). In another 39 patients (42%), initial studies, we analyzed data from quantitative sensory test- symptoms were restricted to the lower extremities for at ing (QST) and immunologic studies. We determined the least several months but later spread to the hands. frequency of CSPN among our referral population and Symptoms confined to the upper extremities were rare, collected data on the clinical course, prognosis, and re- being reported in only 2 patients (2%). In 1 patient, sponse to pharmacological therapy. We also compared symptoms first appeared in the hands and later spread clinical and laboratory data from patients with CSPN with to the feet. Simultaneous development of upper and pain vs those without. lower extremity symptoms occurred in 6 patients (6%). Four patients could not recall the initial distribution of RESULTS their symptoms. Of the 93 patients, 74 (80%) reported progression A total of 402 patients were evaluated for PN in the 2 clin- of their symptoms before our evaluation. The remain- ics during a 2-year period, 93 (23%) of whom (44 women ing patients (20%) believed their symptoms had im- and 49 men) met entry criteria for CSPN. At presenta- proved or reached a plateau. tion, mean age was 63.2 years (range, 37.0-94.0 years), and mean duration of symptoms was 62.9 months (range, EXAMINATION FINDINGS 3.0-240.0 months). Sensory examination demonstrated abnormal results for PRESENTING SYMPTOMS proprioception in 28 patients (30%), light touch in 50 (54%), pinprick in 69 (74%), and vibration in 79 (85%). Pain with numbness or tingling was the most common Pinprick was the most sensitive modality in assessing the presentation (reported in 58 patients), followed by proximal extent of sensory loss, with 58 patients dem- numbness or tingling without pain (22 patients) and onstrating impairment at the calf, 25 at the knee, 30 in pain alone (9 patients) (Figure 1). Gait unsteadiness the hands, and 11 in the forearms (Figure 2). On mo- ARCH NEUROL / VOL 56, MAY 1999 541 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 1.