RESEARCH ARTICLE
The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations Alon Abraham1, Majed Alabdali2, Abdulla Alsulaiman2, Hana Albulaihe3, Ari Breiner1, Hans D. Katzberg1, Danah Aljaafari2, Leif E. Lovblom4, Vera Bril1*
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1 Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada, 2 Department of Neurology, King Fahad Hospital of the University, University of Dammam, Dammam, Saudi Arabia, 3 Department of Neurology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, 4 Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai, Hospital and Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Canada * [email protected]
Abstract Introduction OPEN ACCESS Citation: Abraham A, Alabdali M, Alsulaiman A, Albulaihe H, Breiner A, Katzberg HD, et al. (2017) The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations. PLoS ONE 12(3): e0171597. doi:10.1371/journal. pone.0171597 Editor: Soroku Yagihashi, Hirosaki Daigaku, JAPAN Received: October 6, 2016 Accepted: January 22, 2017 Published: March 1, 2017 Copyright: © 2017 Abraham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist.
Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results.
Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results.
Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls.
Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of
PLOS ONE | DOI:10.1371/journal.pone.0171597 March 1, 2017
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Sensitivity and specificity of the neurological examination for peripheral neuropathy detection
individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters.
Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be considered minimal essential components of the physical examination in patients with suspected polyneuropathy.
Introduction Despite technological advances, the neurologic evaluation remains first and foremost a bedside exercise[1]. The clinical history and the neurologic examination play an important role in the diagnosis of various nervous system diseases. The crystallization of an accurate clinical picture regarding localization, is unique for the field of neurology, and does not occur to the same degree in any other branch of medicine[1]. Polyneuropathy is one of the most prevalent neurologic disorders, with an overall prevalence of 2.4%, increasing to 8% in people older than 55 years[2]. Polyneuropathy most commonly presents with sensory symptoms, occasionally accompanied by weakness, typically in a distal symmetric distribution. However, symptoms alone have a relatively poor diagnostic accuracy in predicting the presence of polyneuropathy, and the most accurate diagnosis is made by a combination of neuropathic symptoms and signs, and electrophysiological findings[3]. Nonetheless, patients with polyneuropathy restricted to small nerve fibers, have minimal findings on the neurological examination, such as reduced pinprick or temperature sensation, and normal nerve conduction studies, making the diagnosis of small fiber neuropathy challenging[4]. The neurological examination is relatively inexpensive, but nonetheless may reveal more than the most expensive laboratory tests and imaging studies. However, the examination is more art than science, as limited evidence supports its value, and therefore additional research has been recommended[5]. Previous studies have shown excessive variability and over-diagnoses of signs, [6], which improves by using unequivocally abnormal signs and symptoms, and taking age, sex, and physical variables into account.[7] Although several studies have explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients, most frequently those with diabetic polyneuropathy, and have not explored the correlation between examination findings and symptoms and electrophysiological results[3]. The purpose of this study was to explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, and to find the most sensitive combination of examination components which could be used to screen for polyneuropathy. In addition, we aimed to correlate examination findings with symptoms and electrophysiological results, in order to determine whether neurologic examination findings also correlate with polyneuropathy severity.
Materials and methods In this study, we extracted the demographic data, clinical history, and neurological and electrophysiological findings of 312 patients diagnosed with polyneuropathy. All patients
PLOS ONE | DOI:10.1371/journal.pone.0171597 March 1, 2017
2 / 11
Sensitivity and specificity of the neurological examination for peripheral neuropathy detection
attended the Prosserman Family Neuromuscular clinic, Toronto General Hospital, University Health Network from January 2013 to September 2015. In addition, 47 control subjects, attending the clinic from February 2015 to August 2016, were examined. The Research Ethics Board of the University Health Network approved the current study protocol and waived informed consent for polyneuropathy patients, which were studied retrospectively. All control subjects were recruited prospectively as part of another study evaluating patients with 50 or more years of type I diabetes duration, for future biomarker studies, and provided informed consent. Inclusion criteria for patients with polyneuropathy included a diagnosis of polyneuropathy in symptomatic patients who had confirmation by electrophysiological findings (reference standard). Patients with mononeuropathies or pure small fiber neuropathy were excluded from this study. The reason for exclusion of patients with small fiber neuropathy was the relatively nonspecific presentation, combined with minor or no neurological findings and normal nerve conduction studies, making a definitive diagnosis challenging[4]. Although small fiber neuropathy can be confirmed by skin punch biopsy[8], or other specialized tests for small nerve fiber function[9], those were not assessed in this study. In addition, the minimal neurological examination findings and the normal nerve conduction studies do not allow correlation of examination findings with symptoms and nerve conduction studies, so that this patient subgroup is not relevant for the current study objectives. Control subjects were age- and gender- matched with type 1 diabetes patients from a different study. Exclusion criteria included the presence of diabetes, or symptoms or electrophysiological evidence suggestive for polyneuropathy. Specifically, subjects with a clinical history of sensory symptoms, ataxia, or weakness were excluded. In addition, subjects with a sural sensory nerve action potential (SNAP) amplitude
The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations Alon Abraham1, Majed Alabdali2, Abdulla Alsulaiman2, Hana Albulaihe3, Ari Breiner1, Hans D. Katzberg1, Danah Aljaafari2, Leif E. Lovblom4, Vera Bril1*
a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
1 Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Canada, 2 Department of Neurology, King Fahad Hospital of the University, University of Dammam, Dammam, Saudi Arabia, 3 Department of Neurology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, 4 Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai, Hospital and Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Canada * [email protected]
Abstract Introduction OPEN ACCESS Citation: Abraham A, Alabdali M, Alsulaiman A, Albulaihe H, Breiner A, Katzberg HD, et al. (2017) The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations. PLoS ONE 12(3): e0171597. doi:10.1371/journal. pone.0171597 Editor: Soroku Yagihashi, Hirosaki Daigaku, JAPAN Received: October 6, 2016 Accepted: January 22, 2017 Published: March 1, 2017 Copyright: © 2017 Abraham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist.
Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results.
Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results.
Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls.
Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of
PLOS ONE | DOI:10.1371/journal.pone.0171597 March 1, 2017
1 / 11
Sensitivity and specificity of the neurological examination for peripheral neuropathy detection
individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters.
Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be considered minimal essential components of the physical examination in patients with suspected polyneuropathy.
Introduction Despite technological advances, the neurologic evaluation remains first and foremost a bedside exercise[1]. The clinical history and the neurologic examination play an important role in the diagnosis of various nervous system diseases. The crystallization of an accurate clinical picture regarding localization, is unique for the field of neurology, and does not occur to the same degree in any other branch of medicine[1]. Polyneuropathy is one of the most prevalent neurologic disorders, with an overall prevalence of 2.4%, increasing to 8% in people older than 55 years[2]. Polyneuropathy most commonly presents with sensory symptoms, occasionally accompanied by weakness, typically in a distal symmetric distribution. However, symptoms alone have a relatively poor diagnostic accuracy in predicting the presence of polyneuropathy, and the most accurate diagnosis is made by a combination of neuropathic symptoms and signs, and electrophysiological findings[3]. Nonetheless, patients with polyneuropathy restricted to small nerve fibers, have minimal findings on the neurological examination, such as reduced pinprick or temperature sensation, and normal nerve conduction studies, making the diagnosis of small fiber neuropathy challenging[4]. The neurological examination is relatively inexpensive, but nonetheless may reveal more than the most expensive laboratory tests and imaging studies. However, the examination is more art than science, as limited evidence supports its value, and therefore additional research has been recommended[5]. Previous studies have shown excessive variability and over-diagnoses of signs, [6], which improves by using unequivocally abnormal signs and symptoms, and taking age, sex, and physical variables into account.[7] Although several studies have explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients, most frequently those with diabetic polyneuropathy, and have not explored the correlation between examination findings and symptoms and electrophysiological results[3]. The purpose of this study was to explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, and to find the most sensitive combination of examination components which could be used to screen for polyneuropathy. In addition, we aimed to correlate examination findings with symptoms and electrophysiological results, in order to determine whether neurologic examination findings also correlate with polyneuropathy severity.
Materials and methods In this study, we extracted the demographic data, clinical history, and neurological and electrophysiological findings of 312 patients diagnosed with polyneuropathy. All patients
PLOS ONE | DOI:10.1371/journal.pone.0171597 March 1, 2017
2 / 11
Sensitivity and specificity of the neurological examination for peripheral neuropathy detection
attended the Prosserman Family Neuromuscular clinic, Toronto General Hospital, University Health Network from January 2013 to September 2015. In addition, 47 control subjects, attending the clinic from February 2015 to August 2016, were examined. The Research Ethics Board of the University Health Network approved the current study protocol and waived informed consent for polyneuropathy patients, which were studied retrospectively. All control subjects were recruited prospectively as part of another study evaluating patients with 50 or more years of type I diabetes duration, for future biomarker studies, and provided informed consent. Inclusion criteria for patients with polyneuropathy included a diagnosis of polyneuropathy in symptomatic patients who had confirmation by electrophysiological findings (reference standard). Patients with mononeuropathies or pure small fiber neuropathy were excluded from this study. The reason for exclusion of patients with small fiber neuropathy was the relatively nonspecific presentation, combined with minor or no neurological findings and normal nerve conduction studies, making a definitive diagnosis challenging[4]. Although small fiber neuropathy can be confirmed by skin punch biopsy[8], or other specialized tests for small nerve fiber function[9], those were not assessed in this study. In addition, the minimal neurological examination findings and the normal nerve conduction studies do not allow correlation of examination findings with symptoms and nerve conduction studies, so that this patient subgroup is not relevant for the current study objectives. Control subjects were age- and gender- matched with type 1 diabetes patients from a different study. Exclusion criteria included the presence of diabetes, or symptoms or electrophysiological evidence suggestive for polyneuropathy. Specifically, subjects with a clinical history of sensory symptoms, ataxia, or weakness were excluded. In addition, subjects with a sural sensory nerve action potential (SNAP) amplitude
