Peripheral Nerve Pathology Research Articles

Peripheral nerve and neuromuscular junction pathology in Pompe disease.

Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation. Respiratory and ambulatory dysfunction are prominent features in patients with Pompe yet the mechanism defining the development of muscle weakness is currently unclear. Transgenic animal models of Pompe disease mirroring the patient phenotype have been invaluable in mechanistic and therapeutic study. Here, we demonstrate significant pathological alterations at neuromuscular junctions (NMJs) of the diaphragm and tibialis anterior muscle as prominent features of disease pathology in Gaa knockout mice. Postsynaptic defects including increased motor endplate area and fragmentation were readily observed in Gaa(-/-) but not wild-type mice. Presynaptic neuropathic changes were also evident, as demonstrated by significant reduction in the levels of neurofilament proteins, and alterations in axonal fiber diameter and myelin thickness within the sciatic and phrenic nerves. Our data suggest the loss of NMJ integrity is a primary contributor to the decline in respiratory and ambulatory function in Pompe and arises from both pre- and postsynaptic pathology. These observations highlight the importance of systemic phenotype correction, specifically restoration of GAA to skeletal muscle and the nervous system for treatment of Pompe disease.

P214: Study of sympathetic skin response in diabetic patients with soft tissue rheumatism of the hand

P214: Study of sympathetic skin response in diabetic patients with soft tissue rheumatism of the hand

Peripheral Nerve Surgery - View through Multidiciplinary Approch Window

Modern surgical treatment of peripheral nerves begins with introduction of operative microscope in 1964. Pathology of peripheral nerves is a broad field of neurosurgery and includes injuries, tumors and compressive neuropathies. Indications for operative treatment of peripheral nerve injuries are open injuries with undoubtable nerve injury and neurological deficit, closed injuries that show no sign of recovery even three months after injury, pain that is resistant to therapy. Good preoperative evaluation, detailed examination, electrophysiological studies, neuroradiography and multidisciplinary approach is an imperative. In our Clinic many different procedures are done: neurolysis, direct suture, nerve transplantation, nerve transfer. Treatment of choice is different for every patient and it is individually selected. After surgery, of utmost importance for neurological recovery is physical rehabilitation. Poorer results are when mixed nerves are involved, traction injuries and higher lesions. Timing of the surgical treatment is of the utmost importance. Surgery of brachial plexus injuries is utterly demanding field of surgery. Treatment should be conservative in patients that show spontaneous recovery within the first few weeks after the trauma. Surgical treatment is indicated for patients who have an associated vascular lesion and sharp wounds, where lesion on neural elements is evident. Immediate repair, when possible, is a better therapeutic approach than delayed repair. A closed injury without evidence of root avulsion should be treated surgically, if there is no sign of recovery within 6 months. The selective combination of neurotizations gives a moderate shoulder and elbow control. Compressive neuropathies are a group of disorders of the peripheral nerves that are characterized by pain and/or loss of function (motor and/or sensory) of the nerves as a result of chronic compression. Nerve conduction studies confirm the diagnosis. Some compression neuropathies can be treated surgically -carpal tunnel and cubital tunnel syndrome are two most common examples. Surgery is recommended for patients with symptoms refractory to non-operative measures and/or those with severe and long-standing symptoms or weakness. Tumors of peripheral nerves are rare lesions. They are more frequent in phakomatoses. Patients present for evaluation of peripheral nerve tumors because of a soft tissue mass, pain, or focal neurologic findings. The duration and progression of symptoms or signs is important as most benign tumors have a longer duration and a slow rate of progression, while malignant tumors tend to progress rapidly in size, amount of pain, and neurologic deficit. A careful family history is important in the assessment of an underlying neurogenetic disorder. Treatment of choice is total surgical resection. In certain types of tumors, that affect majority of nerve fascicles (e.g., neurofibroma), resection of nerve must be done to obtain total surgical resection. In this case nerve defect should be repaired using nerve grafting or nerve transfer. In malignant tumors, nerve reparation is not advisable.

Molecules involved in the crosstalk between immune- and peripheral nerve Schwann cells.

Schwann cells are the myelinating glial cells of the peripheral nervous system and establish myelin sheaths on large caliber axons in order to accelerate their electrical signal propagation. Apart from this well described function, these cells revealed to exhibit a high degree of differentiation plasticity as they were shown to re- and dedifferentiate upon injury and disease as well as to actively participate in regenerative- and inflammatory processes. This review focuses on the crosstalk between glial- and immune cells observed in many peripheral nerve pathologies and summarizes functional evidences of molecules, regulators and factors involved in this process. We summarize data on Schwann cell's role presenting antigens, on interactions with the complement system, on Schwann cell surface molecules/receptors and on secreted factors involved in immune cell interactions or para-/autocrine signaling events, thus strengthening the view for a broader (patho) physiological role of this cell lineage.

Rhesus Cytomegalovirus (Macacine Herpesvirus 3)–Associated Facial Neuritis in Simian Immunodeficiency Virus–Infected Rhesus Macaques (Macaca mulatta)

Peripheral neuropathies are common sequelae to human immunodeficiency virus (HIV) infection in humans and are due to a variety of mechanisms, including direct antiretroviral toxicity, HIV-mediated damage, immune-mediated disorders, and opportunistic viral infections. Rhesus macaques (Macaca mulatta) infected with simian immunodeficiency virus (SIV) remain the most consistent animal model for unraveling the pathogenesis of lentiviral-associated disease and its associated opportunistic infections. Rhesus cytomegalovirus (RhCMV) is the most common opportunistic viral infection in rhesus macaques infected with SIV and causes multiorgan pathology; however, its role in peripheral nerve pathology has not been explored. We have identified 115 coinfected cases with SIV and RhCMV, of which 10 cases of RhCMV-associated facial neuritis were found (8.7% prevalence). Histologic lesions were consistent in all cases and ranged from partial to complete obliteration of the nerves of the tongue, lacrimal gland, and other facial tissues with a mixed inflammatory population of neutrophils and macrophages, of which the latter commonly contained intranuclear inclusion bodies. Luxol fast blue staining and myelin basic protein immunohistochemistry confirmed the progressive myelin loss in the peripheral nerves. Bielschowsky silver stain revealed progressive loss of axons directly related to the severity of inflammation. Double immunohistochemistry with spectral imaging analysis revealed RhCMV-infected macrophages directly associated with the neuritis, and there was no evidence to support RhCMV infection of Schwann cells. These results suggest that peripheral nerve damage is a bystander effect secondary to inflammation rather than a direct infection of Schwann cells and warrants further investigations into the pathogenesis of RhCMV-induced peripheral neuropathy.

A Method for Establishing an Animal Model of Like-Auditary Neuropathy

Objective:To establish an animal model of like-auditory neuropathy in neonatal rat. MethodsThe animals were injected with phenylhydrazine hydrochloride or saline at 7-day of age. ABR and DPOAE were performed to assess the auditory function. The cochlea basilar membrane stretched preparation and cochlear frozen sections were prepared for immunohistochemical staining to examine the morphological change of hair cells and spiral ganglion cells (SGNs). ResultsAt 7-day age the ABR waveI, III, V, latencies andI- III,I-V IWIs in the experimental group were significantly prolonged compared with those in the control group. The ABR thresholds were also elevated in the experimental group. We found there is no significant difference in DPOAE in phenylhydrazine hydrochloride exposure group compare to control group. The cochlear hair cells showed no signs of loss in both group, but the total number of neurofilaments positive cells in SGNs were significantly reduced in the phenylhydrazine treated animals. ConclusionOur study suggests that phenylhydrazine hydrochloride can change the auditory function and induce peripheral nerve pathology by targeted mainly the SGNs in neonatal rat.

Mitochondrial Dynamics in Peripheral Neuropathies

Mitochondrial dynamics describes the continuous change in the position, size, and shape of mitochondria within cells. The morphological and functional complexity of neurons, the remarkable length of their processes, and the rapid changes in metabolic requirements arising from their intrinsic excitability render these cells particularly dependent on effective mitochondrial function and positioning. The rules that govern these changes and their functional significance are not fully understood, yet the dysfunction of mitochondrial dynamics has been implicated as a pathogenetic factor in a number of diseases, including disorders of the central and peripheral nervous systems. In recent years, a number of mutations of genes encoding proteins that play important roles in mitochondrial dynamics and function have been discovered in patients with Charcot-Marie-Tooth (CMT) disease, a hereditary peripheral neuropathy. These findings have directly linked mitochondrial pathology to the pathology of peripheral nerve and have identified certain aspects of mitochondrial dynamics as potential early events in the pathogenesis of CMT. In addition, mitochondrial dysfunction has now been implicated in the pathogenesis of noninherited neuropathies, including diabetic and inflammatory neuropathies. The role of mitochondria in peripheral nerve diseases has been mostly examined in vitro, and less so in animal models. This review examines available evidence for the role of mitochondrial dynamics in the pathogenesis of peripheral neuropathies, their relevance in human diseases, and future challenges for research in this field.

1. Ultrasound combined with clinical neurophysiology in peripheral nerve pathologies: When it is worth? Preliminary data in 50 outpatients

Our aim was to assess the relevance of nerve ultrasonography in a clinical neurophysiological consultation. Patients with a diagnosis of entrapment and/or post-traumatic neuropathy, but with clinical or neurophysiological unusual findings, were admitted to a nerve ultrasound (US) examination. We recruited 50 neuropathies (25M, 25F): 23 median nerves at the carpal tunnel, 1 anterior interosseous, 14 ulnar nerves at the elbow, 3 brachial plexus, 2 posterior interosseus, 1 superficial radial, 1 superficial peroneal and 4 common peroneal nerves. Overall 20/50 patients had a history of trauma: 4/23 patients with median pathology, 6/14 ulnar, 3/4 common peroneal, 1/2 posterior interosseous and all cases of involvement of the brachial plexus, superficial peroneal and superficial radial nerves. US is advisable in: (1) all patients (40%) with post-traumatic etiology (isolated or associated with other entrapments); (2) severe diseases with not evocable nerve; (3) patients with difficult to detect or diffuse neurophysiological alterations (but with clinical suspect of neuropathy); (4) entrapment neuropathies for screening of: concomitant tenosynovitis showed in 21.7% of carpal tunnel syndromes; dynamic ulnar nerve luxation at the elbow (28.5%); multiple sites of injury (radial, ulnar and posterior interosseous) in all brachial plexus pathologies.

The Utility of Musculoskeletal Ultrasound in Rehabilitation Settings

Aside from its prompt use in musculoskeletal injuries (sports lesions, degenerative/inflammatory joint disorders, and peripheral nerve pathologies), ultrasonographic imaging can be used quite conveniently in various types of rehabilitation conditions as well. If used in a rehabilitation setting, ultrasound can significantly contribute to the diagnostic/therapeutic algorithm of rehabilitation patients. Accordingly, in this article, the authors focus on the diagnostic/interventional utility of ultrasound particularly for shoulder problems, overuse injuries of wheelchair users, heterotopic ossification, amputee follow-up, peripheral nerve and botulinum toxin injections, and diaphragm imaging/electromyography.

Magnetic Resonance Neurography Research

Magnetic resonance neurography (MRN) is a specialized technique that is rapidly becoming part of the diagnostic algorithm of peripheral nerve pathology. However, in order for this modality to be considered appropriate, its value compared with current methods of diagnosis should be established. Therefore, radiologists involved in MRN research should use appropriate methodology to evaluate MRN's effectiveness with a multidisciplinary approach. This article reviews the various tiers of research available to assess the clinical value of a diagnostic modality with an emphasis on how to evaluate the impact of MRN on diagnostic thinking and therapeutic decisions.

Ultrasound vs. MRI for Detecting Focal Peripheral Nerve Pathology

Focal peripheral nerve pathology typically is suspected based on a careful clinical assessment and the results of nerve conduction studies and

Detection of peripheral nerve pathology

To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions.

Autonomic dysfunction is common in HIV and associated with distal symmetric polyneuropathy

Neurologic complications of HIV are well characterized in the central and peripheral nervous systems but not in the autonomic nervous system, perhaps due to the complexities of measuring autonomic function in medically ill populations. We hypothesized that autonomic dysfunction is common in HIV, can be meaningfully measured with an autonomic reflex screen, and is associated with distal symmetric polyneuropathy (DSP) but not with signs of CNS disease. We also sought to characterize immunovirologic and medical factors associated with autonomic dysfunction. We assessed 102 HIV-infected adults for autonomic dysfunction with a laboratory-based autonomic reflex screen summarized as the composite autonomic severity score (CASS). The total neuropathy score (TNS) was used to quantify DSP based on neurologic interview/examination, quantitative sensory testing, and nerve conduction studies. Autonomic dysfunction was common, with a CASS ≥ 3 in 61 % of participants, of whom 86 % were symptomatic. Greater CASS abnormalities demonstrated univariate association with increasing TNS, age, viral load, hypertension, and use of medications (particularly anticholinergics), but not with antiretrovirals, current/nadir CD(4+) count, HIV duration, metabolic factors, or signs of CNS disease. The TNS was the only significant predictor of the CASS in multivariate analysis; anticholinergic medications were marginally significant. This study demonstrates that autonomic dysfunction is common and frequently symptomatic in HIV and that an autonomic reflex screen, adjusted for anticholinergic medication, is useful in its assessment. Association of autonomic dysfunction with DSP suggests common factors in their pathogenesis, and autonomic neuropathy may be part of the spectrum of HIV-associated peripheral nerve pathologies.

Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology

ObjectiveCarpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS.MethodsWe performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics.ResultsFor CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed.ConclusionsOur study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery.

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb.

The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the “elevator technique”. All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the “Journal of Ultrasonography”.

Autosomal dominant congenital spinal muscular atrophy: a true form of spinal muscular atrophy caused by early loss of anterior horn cells

Autosomal dominant congenital spinal muscular atrophy is characterized by predominantly lower limb weakness and wasting, and congenital or early-onset contractures of the hip, knee and ankle. Mutations in TRPV4, encoding a cation channel, have recently been identified in one large dominant congenital spinal muscular atrophy kindred, but the genetic basis of dominant congenital spinal muscular atrophy in many families remains unknown. It has been hypothesized that differences in the timing and site of anterior horn cell loss in the central nervous system account for the variations in clinical phenotype between different forms of spinal muscular atrophy, but there has been a lack of neuropathological data to support this concept in dominant congenital spinal muscular atrophy. We report clinical, electrophysiology, muscle magnetic resonance imaging and histopathology findings in a four generation family with typical dominant congenital spinal muscular atrophy features, without mutations in TRPV4, and in whom linkage to other known dominant neuropathy and spinal muscular atrophy genes has been excluded. The autopsy findings in the proband, who died at 14 months of age from an unrelated illness, provided a rare opportunity to study the neuropathological basis of dominant congenital spinal muscular atrophy. There was a reduction in anterior horn cell number in the lumbar and, to a lesser degree, the cervical spinal cord, and atrophy of the ventral nerve roots at these levels, in the absence of additional peripheral nerve pathology or abnormalities elsewhere along the neuraxis. Despite the young age of the child at the time of autopsy, there was no pathological evidence of ongoing loss or degeneration of anterior horn cells suggesting that anterior horn cell loss in dominant congenital spinal muscular atrophy occurs in early life, and is largely complete by the end of infancy. These findings confirm that dominant congenital spinal muscular atrophy is a true form of spinal muscular atrophy caused by a loss of anterior horn cells localized to lumbar and cervical regions early in development.

Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers

Canine degenerative myelopathy (DM) is an adult-onset, fatal neurodegenerative disease with many similarities to an upper-motor-neuron-onset form of human amyotrophic lateral sclerosis (ALS), that results from mutations in the superoxide dismutase (SOD1) gene. DM occurs in many dog breeds, including the Pembroke Welsh Corgi and Boxer. The initial upper motor neuron degeneration produces spastic paraparesis and affected dogs develop general proprioceptive ataxia in the pelvic limbs. Dog owners usually elect euthanasia when their dog becomes paraplegic. When euthanasia is delayed, lower motor neuron signs including ascending tetraparesis, flaccid paralysis and widespread muscle atrophy emerge. For this study, muscle and peripheral nerve specimens were evaluated at varying disease stages from DM-affected Pembroke Welsh Corgis and Boxers that were homozygous for the SOD1 mutation and had spinal cord histopathology consistent with DM. Comparisons were made with age- and breed-matched control dogs. Here we provide evidence that Pembroke Welsh Corgis and Boxers with chronic DM develop muscle atrophy consistent with denervation, peripheral nerve pathology consistent with an axonopathy, and to a lesser degree demyelination. Canine DM has been proposed as a potential spontaneous animal disease model of human ALS. The results of this study provide further support that canine DM recapitulates one form of the corresponding human disorder and should serve as a valuable animal model to develop therapeutic strategies.

Ultrasound Is Superior to Magnetic Resonance Imaging for Detecting Peripheral Nerve Pathology in Mononeuropathies and Brachial Plexopathies (P06.149)

Objective: Compare accuracy of magnetic resonance imaging (MRI) and ultrasound (US) in detecting peripheral nerve pathology. Background It is unknown whether MRI or US is superior for detecting peripheral nerve pathology. Design/Methods: We reviewed charts of 141 cases referred for neuromuscular US between 6/2007 and 10/2011 for suspected upper and lower extremity mononeuropathy(ies) or brachial plexopathy, excluding idiopathic carpal tunnel syndrome and ulnar neuropathy at the elbow, and identified cases who underwent MRI of the same limb for the same indication as the US. Imaging results were compared to the gold standard of surgical or, if unavailable, clinical/electrodiagnostic evaluation. Results: We identified 52 cases evaluated with both MRI and US. Focal nerve pathology was established in 46 and excluded in six by surgical (39) or clinical/electrodiagnostic evaluation (13). Diagnoses included peripheral nerve sheath tumors (18), traumatic (10) or idiopathic (8) neuropathy, fibrosis (4), compression by ganglion/synovial cysts (4) or other soft-tissue structures (3), non-nerve soft tissue tumor (3), intraneural granuloma (1) and vasculitis (1). US was more sensitive than MRI (93 vs. 70%) and equally specific (both 83%). Pathology accurately identified on US but not MRI included nerve enlargement (7), peripheral nerve sheath tumor (3), compression by anomalous muscle (1), and a hemangioma identified as non-nerve pathology on US but not MRI. Of these 12 cases with inaccurate MRI but not US, eight (67%) had lesions larger than two centimeters; only two lesions were outside the field of view of the MRI. In three cases classified as accurate for a single lesion on both MRI and US, US identified 11 additional lesions (multifocal neurofibromas, nerve enlargements, and fibrous thickening) not seen on MRI. Conclusions: Ultrasound is more sensitive, has equivalent specificity, and may better identify multifocal lesions than MRI in suspected mononeuropathies and brachial plexopathies. Supported by: This publication was made possible in part by the Washington University Neuromuscular Research Fund and the Grant Number UL1RR024992 from the NIH-National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Disclosure: Dr. Zaidman has nothing to disclose. Dr. Seelig has nothing to disclose.

Ultrasonography of the peripheral nervous system

With improvements in ultrasound (US) imaging equipment and refinements in scanning technique, an increasing number of peripheral nerves and related pathologic conditions can be identified. Modern US imaging supports the clinical examination and electrophysiologic testing in setting the diagnosis, and enhances this information by illuminating the morphological aspects and etiology of peripheral nerve pathology. US can readily be used for detection of nerve abnormalities caused by trauma, tumors, inflammation and a variety of nonneoplastic conditions, including compressive neuropathies. Well recognized advantages of the method such as the possibility of a dynamic examination, assessing long nerves segments in a short time, bed-side-availability, non-invasivity and low cost, make US the ideal imaging tool in peripheral nerve disease.

Pitfalls in Using Electrophysiological Studies to Diagnose Neuromuscular Disorders

Electrodiagnostic testing is used widely for the full characterization of neuromuscular disorders and for providing unique information on the processes underlying the pathology of peripheral nerves and muscles. However, such testing should be considered as an extension of anamnesis and physical examination, not as pathognomonic of a specific disease entity. There are many pitfalls that could lead to erroneous interpretation of electrophysiological study results when the studies are not performed properly or if they are performed in the presence of anatomical aberrations. The diagnostic reliability of electrodiagnostic studies can be improved and the associated pitfalls overcome if the physician is familiar with all of those possible pitfalls. In this article we discuss the most common and important pitfalls associated with electrodiagnostic medicine.