Focal neuropathies-constitutional risk factors and new sensory neurography techniques

Abstract

Focal peripheral neuropathies are common disorders in EMG examinations. They are caused by temporary or chronic compression, trauma, immune mediated mechanisms, vasculitis, infections, and tumours. Many factors predispose individuals to focal neuropathies. Some are constitutional, like age, gender, and body mass index; others have been related to concurrent diseases (e.g., diabetes, rheumatoid arthritis and cancer). Occupation, physical activity, trauma, surgery, and pregnancy may also contribute to the development of focal neuropathies. The relationship between body mass index (BMI), age, height, gender and focal neuropathies has been studied by several authors. Obesity is a risk factor for carpal tunnel syndrome (CTS) and meralgia paresthetica (MP). Other studies suggest that lean subjects have an increased risk for ulnar neuropathy at the elbow (UNE) and peroneal nerve injury at the fibular head. However, many of the previous studies are contradictory. Richardson et al. found no correlation between BMI and UNE. Many studies indicate that older age and female gender are risks factors for CTS and Morton´s metatarsalgia (MTA), while others have been unable to confirm this finding. Low back pain and lumbar radiculopathies seem to be more common in older and overweight people. Neuropathies around the shoulder are usually caused by NA and trauma, but no studies exist on the influence of age, gender and BMI as the risk factors on these neuropathies. Carpal tunnel syndrome (CTS), ulnar neuropathy (UN), radial neuropathy, cervical radiculopathy, suprascapular neuropathy and long thoracic nerve neuropathy are the most common focal neuropathies in the upper extremity. Peroneal neuropathy, meralgia parestethica, Morton´s neuralgia and lumbar radiculopathy are the most common in the lower extremity. The anatomy is an important predisposing factor, for instance, narrow passages (in patients with CTS and UNE), proximity to bone in radial neuropathy following to trauma of the humerus bone and no protective subcutaneous tissue as we can see in peroneal nerve at the fibula. Other important predisposing factors related with the patient are: the constitution (obesity...), fractures, polyneuropathies, occupation, past-time activities,... There are different methods to define obesity, but The National Institutes of Health guidelines have been proposed to categorize the weight status using the body mass index (BMI), which is calculated as weight in kilograms divided by height in meters squared. A BMI over 30 kg/m2 defines obesity, while values between 25 and 29.9 kg/m2 are considered overweight. Morbid obesity is defined as BMI greater than 40 kg/m21. Numerous epidemiological studies have demonstrated the relationship between BMI and increased mortality and morbidity2. When body weight increases by 20% on average, the mortality rate increases by 20% in men and 10% in women. Certain comorbid conditions have been associated with obesity such as hypertension, coronary artery disease, DM, Sd. Pickwick, thromboembolic disease,... The supraclavicular nerve (SCN) is a superficial sensory nerve originating from the C3 and C4 nerve roots of the superficial cervical plexus. This nerve arborizes proximal to the clavicle and divides into medial, intermediate , and lateral branches providing sensation over the clavicle, anteromedial shoulder and proximal chest. Because the SCN lies in close proximity to the clavicle, it is particularly vulnerable to be damage in cases of clavicle fracture and in operative of treatment of such fratures. Surgery for clavicular shaft fracture is becoming more common but incisional and chest Wall numbness reportedly occurs in 10% to 29% of patients. This may be the result of iatrogenic injury to the supraclavicular nerve branches. The development of painful neuromas after iatrogenic transsection and symptomatic nerve entrapment in fracture callus after healing have previously been described. This study’s aim was to study to what extent BMI, age, height and gender are risk factors for focal neuropathies in a large group of patients (9686) referred for EMG. In adition we describe a new neurography tecnique for the diagnosis of supraclavicular neuropathy, provide reference values and demostrate the utility of this tecnique in 2 patients. We retrospectively reviewed all patients referred for EMG during 2.5 years at Turku University Hospital, Finland, University Hospital of Tartu, Estonia and a private clinic (Turun Neurolaboratorio) in Turku, Finland. The doctors participating were all trained at Turku University Hospital’s Department of Clinical Neurophysiology and used identical diagnostic criteria. All three clinics used Dantec Keypoint Classic EMG equipment (Skovlunde, Denmark) with identical methods and reference values. The patient data was extracted from the databases of the EMG systems, and data from the three units were pooled for the analyses. All patients 18 years or older were included in the study and gave informed consent for participation. Only the patients’ first visit was included, and follow-up studies for the same disorder were excluded. The number of patients was 9.686 (58.2% women). The ethical committee of the Hospital District of South –West Finland approved this study. 1.2 Risk factors The Keypoint Classic database included the following patient-related information: gender, height, BMI, and age. The analyses included all four of these constitutional factors. We used World Health Organization cut-off points for BMI: underweight <18.5 kg/m2, normal weight 18.5-24.9 kg/m2, overweight ≥25.0 kg/m2, obese ≥30.0 kg/m2, morbid obese >40 kg/m2. 1.3 Neuropathies studied This study included those focal neuropathies in the upper and lower limbs that occurred in at least 15 patients (Table 1). Brachial and lumbosacral plexopathies were not included, because the diagnosis code did not differentiate between different etiologies. We created a separate group for 76 patients with both UNE and CTS. Patients in this group were also included in the separate UNE and CTS groups. CTS, MP and MTA are chronic entrapment neuropathies. Most long thoracic neuropathies and suprascapular neuropathies are caused by NA. Neuropathies around the shoulder may sometimes also be traumatic. Peroneal neuropathy at the knee and radial neuropathies are mostly caused by temporary compression. UNE is not a homogenous group, as the etiology of ulnar neuropathies is variable. Most UNE are caused by temporary compression during static flexion of the elbow; A few are chronic entrapment neuropathies at the flexor retinaculum of the flexor carpi ulnaris muscle (cubital tunnel), and some are caused by arthrosis of the elbow (“tardy ulnar palsy”). Our database does not differentiate between these different etiologies. 1.4 Control group The patients with no EMG abnormalities served as controls in testing for effects of age, height and BMI. These factors were separately analyzed for men and women. 1.5 Statistical analysis We performed the statistical analyses using R (www.r-project.com), a language and environment for statistical computing and graphics. We calculated the percentage and ratio of men and women in every neuropathy, and we calculated the means and standard deviations of each variable separately by gender. T-test was used to compare groups with continuous variables, such as BMI, age and height. We have calculated odds ratio by median-unbiased estimation and exact confidence interval, using the mid-p method. Normal BMI has been used as the reference class for odds ratio calculations. 1.6 For multiple comparisons, oddsratio function - , included in epitools package (an epidemiology tools package built on R), w - was used for odds ratio computations (https://cran.r-project.org/package=epitools) for different BMI subclasses. 2 Results Table 1 summarizes the demographic data and the main results of the whole study group, of the groups with normal and abnormal EMG findings, and the diagnostic subgroups according to the risk factors. Table 1 also shows the percentages of each neuropathy in men and women. Table 2 shows the odds ratios (OR) for the different focal neuropathies in relation to BMI, classified as underweight, normal, or overweight. The EMG examination was normal in 4.436 patients (66 % women); 5.250 patients had abnormal EMG findings (52% women). Patients of both genders with EMG abnormalities had higher BMI and were older than the patients with normal EMG findings (Table 1). CTS, by far the most frequent neuropathy, was found in 17% of the patients. Both women and men with CTS had higher BMI than the group with normal findings (Table 1). The majority (72 %) of CTS patients had abnormally high BMI (Table II), 612 patients (38%) were overweight, 491 (30%) were obese and 54 (3%) had morbid obesity. CTS was more common in women (65%) with a ratio of 1,8. The patients with CTS were also older than the control group (Table 1). Conversely, UNE was more common in men (64%) than in women (36%). The patients with UNE were older than the control group (Table 1). High BMI was a risk factor for UNE in both men (p<0.001) and women (p<0.05) (Table 1). Only 4% of patients with UNE were underweight; however, 39% were overweight, 27% were obese with OR 1.7 and 2% patients were morbidly obese (Table 2). Gender distribution did not differ in patients with a combination of CTS and UNE (45% women; Table 1); however, older age increased the risk of simultaneous CTS and ulnar neuropathy in both genders (Table 1). Higher BMI was an additional risk factor only in men (Table 1) in this subgroup. Gender, age and BMI were found not to be risk factors for radial neuropathy (Table 1). After CTS, cervical radiculopathy was the second most common neuropathy in upper limbs. Gender and BMI were not found to be risk factors in this group; however, older age increased the risk of cervical radiculopathy (Table 1). Axillary neuropathy, found in only 16 patients, was the least common neuropathy included in our study and was unrelated to any of the analyzed risk factors (Table 1). Suprascapular neuropathy was much more common in men (75%; Table 1). It was most often found in young men with normal weight; overweight even reduced the risk of this neuropathy (Table 2). Also long thoracic neuropathy was also much more frequent in men (76%; Table 1). Young age and normal BMI were found to increase the risk of long thoracic neuropathy in both genders. There were no patients with BMI ≥30.0 kg/m2 with this neuropathy (Table 2). Lumbar radiculopathy was the second most common neuropathy after CTS and the most common EMG finding in lower limbs. Gender difference was not found in lumbar radiculopathies. Both men and women with lumbar radiculopathy were older and had a somewhat higher BMI than the control subjects (Table 1): 42% were overweight, 27 % were obese and 2% had morbid obesity (Table 2). Peroneal neuropathy was slightly more common in men (59%), while age and BMI were not risk factors (Table 1). MTA was much more common in women (85%) with a ratio of 5,75. Women in the MTA group were also older than the women in the control group (Table 1). MP was nearly equally common in men and women, with a ratio of 1.12 . Both genders with MP had a higher BMI, around 30 kg/m2, and BMI was the single most significant risk factor found in patients with this neuropathy. No underweight patients had MP, as the majority of these patients (74%) were overweight up to morbid obesity (Table 2). 3 Discussion This study shows that many of the common focal neuropathies in patients referred for EMG are related to BMI, gender and age. Although the study is retrospective, it represents a large cohort and a wide spectrum of patients with focal peripheral neuropathies commonly encountered in the EMG laboratory. All medical specialities, even general practitioners, can refer their patients for EMG in the catchment areas studied. Our understanding is that most patients with focal peripheral neuropathies in our catchment areas are referred for an EMG. However, all patients with lumbar and cervical radiculopathies are not routinely referred for EMG; only patients with atypical symptoms or unclear imaging studies are usually referred. Women were more often referred for an EMG examination than men in our laboratories, and they also more often had normal EMG findings, as has been previously reported. The absolute number of patients with abnormal EMG findings was, however, almost equal in women and men. A significant, genderrelated referral bias existed for reasons we can only speculate on. Women more often have pain complaints due to fibromyalgia and other non-specific pain disorders. Women may also seek help more actively from doctors for their problems and demand tests to be done. Overall, the patients with abnormal EMG findings were older and had higher BMI than those with normal findings, but there were interesting deviations from this pattern. Suprascapular and long thoracic neuropathies, which are usually caused by NA, were more often found in young men with normal weight. An additional interesting finding was the high prevalence of the coexistence of CTS and UNE together, which was more common in older men with high BMI. 3.1 BMI Overweight, obese and morbidly obese patients had an increased risk for CTS, UNE, a combination of CTS and UNE, MP and lumbar radiculopathy. In line with some previous studies, BMI was found to be a significant risk factor for CTS in both genders, not only in women, as many studies previously reported. The association of both overweight and obesity with lumbar radicular pain in both men and women is well known, and our results confirm these studies. An increased BMI was a risk factor for MP in our study, a result similar to what has previously been published. MP is a frequent neuropathy associated with obesity, advancing age, and diabetes mellitus. Preventive health care with weight loss counselling could be effective in reducing the frequency of MP. Suprascapular and long thoracic neuropathies were related with normal weight. These neuropathies are usually caused by NA in our experience, but we do not have information on the exact etiology in our material. Our findings suggest that normal weight may increase the risk for NA, while obesity reduced the risk for these neuropathies. We are unaware of any studies on associations between BMI and the occurrence of NA. 3.2 Age According to previous studies, both men and women with CTS, lumbar and cervical radiculopathies, UNE, and the combination of UNE and CTS, were older than the control subjects. However, studies exist that found no relation between UNE and age or it was seen only in men but not in women. Women with MTA were also older than the control subjects. Lumbar and cervical radiculopathies were related to older age, which is in line with the published findings. This can be related to the fact that cervical and lumbar radiculopathies are caused mainly by disc herniation, arthrosis and sometimes by stenosis. 3.3 Gender It is well known that CTS is more frequently seen in women than in men. Several reasons exist for this: some may be hormonal, some related to the wrist anatomy, others are related with occupation. Carpal tunnel syndrome in women is most common around the age of 50 years during the menopause. Hormonal changes at this age may affect the anatomy of the carpal tunnels and the flexor tendons in the tunnel. Occupational factors are also important, as CTS is common in manual workers. Ulnar neuropathies were more common in men, which is in line with some earlier observations. However, Bartels et al. found no relation to gender. MTA was one of the most common neuropathies in our laboratories, which may seem surprising. This is because we have a long tradition of testing for this neuropathy, and our orthopaedic surgeons frequently refer these patients for EMG. In our material, 85% of the patients were women, which corresponds well with other studies that report clear female preponderance (83% - 96%). MTA is usually seen in the feet with hallux valgus and hammer toes, both of which are more common in women. Radial neuropathy, peroneal neuropathy and radiculopathies were more common in men. Radial neuropathy is usually a ‘Saturday night palsy caused by temporary compression during sleep. Peroneal neuropathy is also usually caused by temporary compression during squatting or sitting with legs crossed for extended periods. Suprascapular neuropathy and long thoracic neuropathy were much more common in young men. Our database does not code for the etiology of these neuropathies, which are most likely caused by NA or trauma. NA occurs twice as often in men than women, which probably explains this gender difference. Isolated axillary neuropathy is usually caused by humerus luxation. This neuropathy was more common in men but we do not have information on the etiology of this neuropathy in our material. 3.4 Height Height was not a risk factor for any of the neuropathies studied, except for CTS and suprascapular neuropathy in men. The difference in height between men with CTS and control men was 1 cm. These findings probably represent incidental statistical findings. 3.5 Summary Understanding constitutional risk factors for various focal neuropathies is important for the doctor planning an EMG. An obese, older, or overweight woman with complaints of paresthesias or numbness in the hand has a very high probability of having CTS, whereas MTA in a young man is unlikely. We believe that the identification of BMI as a significant predictive factor in several common peripheral neuropathies is important not only for the diagnostics but also for the prevention and treatment of these conditions. In some neuropathies, losing weight could be a rational treatment, particularly in MP. In addition, the 3 supraclavicular nerve branches could be studies in all subjects. We provide reference values for young subjects and verifying SCN lesions in 2 patients which means that it is a useful technique.