For a list of the blood tests that Massachusetts General Hospital often recommends for patients with small fiber polyneuropathy (SFPN): Blood Tests for Neuropathy. They include:
Complete blood count measures the number of different blood cells. Abnormal results can suggest particular diseases including vitamin B12 deficiency or blood cancers.
Comprehensive metabolic panel
High blood or urine glucose levels suggest diabetes or pre-diabetes. Diabetes is the most common cause of small-fiber, and other types of neuropathy, in developed countries. This diagnosis should always be considered in any patient diagnosed with peripheral neuropathy. Ideally blood glucose should be measured in the morning after an overnight fast. Early diabetes symptoms include excess thirst and urination, weight loss or weight gain. “BUN” and creatinine measure how well your kidneys are working. Poor kidney function can cause neuropathy or influence treatment.
Thyroid Function Test measures hormones secreted by the thyroid gland in the throat. Too high and too low levels of thyroid hormones are associated with peripheral neuropathy. Symptoms of hypothyroidism include cold intolerance, weight gain, constipation, dry skin and hair loss, depression, weakness, as well as neuropathies. Symptoms of hyperthyroidism include weight loss, anxiety, poor sleep, as well as neuropathy. Both conditions can be effectively treated.
Tests for vitamin levels
Low vitamin B12 levels (deficiency) can cause neuropathy as well as anemia, weakness, spinal cord and psychiatric symptoms. Methylmalonic acid levels may be measured as well. Too high levels of vitamin B6 can cause neuropathy. Thiamine deficiency mostly causes motor neuropathy (weakness). Often these can be corrected, which can improve or at least prevent further worsening of neuropathy.
Tests for metals and minerals
These may be performed using urine or blood. High levels of lead, mercury, thallium, zinc, and arsenic, or low levels of copper have all been associated with peripheral neuropathy. Patients typically develop other problems as well, such as hair loss with thallium. Often metal toxicities can be treated to improve or at least prevent worsening of neuropathy.
Tests for inflammation and autoimmunity
This class of diseases is more common in women, particularly during the child-bearing years, than men. Autoimmune diseases often travel together with some patients having several conditions. Systemic autoimmune conditions often affect several organs of the body including the skin, brain, kidney, and eyes. These diseases are often treated with immunomodulatory therapies, and if a patient’s neuropathy is caused by an immune condition, it may improve as well.
Erythrocyte sedimentation rate measures the “stickiness” of your red blood cells. A high value can indicate inflammatory and autoimmune disorders among others.
Antinuclear antibodies, ANA, can indicate Systemic Lupus Erythematosus (SLE), which often includes symptoms such as butterfly-like skin rash on the face, fever, fatigue, weight loss, joint and muscle pains and skin sensitivity to sun exposure, as well as neuropathy. Further testing for lupus may include looking for anti-double stranded DNA or anti-Smith antibodies which are specific to SLE. Other immune disorders including Sjögren’s syndrome and rheumatoid arthritis can also cause patients to have ANA.
Anti-Ro (SS-A) and anti-La (SS-B) are specific antibodies linked to Sjögren’s syndrome. This typically causes dry mouth and dry eyes, and various types of neuropathy are common. Patients can have Sjögren’s syndrome even if these tests are negative (seronegative Sjögren’s). Other tests often performed to look for Sjögren’s include special examinations of the eye, and a biopsy of the salivary glands within the lower lip.
IgA anti-tissue transglutaminase antbodies (IgA-TTG): The presence of these antibodies usually indicates that a patient has celiac sprue. This is an autoimmune disorder in which the body cannot tolerate gluten, a protein found in wheat and barley. Common symptoms are diarrhea, weight loss, anemia, and other symptoms associated with nutritional deficiencies including peripheral neuropathy. In celiac, inflammation can damage the lining of the intestines, leading to poor absorption of nutrients and often to gastrointestinal symptoms. Fortunately, a gluten-free diet is very effective in permitting the gut to heal and improving associated symptoms.
C-reactive proteins: High levels can indicate infection or inflammation.
Tests for infections
HIV testing: The U.S. Centers for Disease Control and Prevention (CDC) recommends this for everyone aged 13-64 regardless of symptoms, but HIV infection is a common cause of neuropathy, so testing should be strongly considered when neuropathy is diagnosed. HIV is highly prevalent in the developing world. Only 1 in 5 of people living with HIV know their status and only 1 in 4 are receiving adequate care. In the United States about 1.2 million people are living with HIV and 50,000 cases are diagnosed every year. Thus, HIV along with its complications- including HIV neuropathy- is a concern in the health providers’ community. The first test is antibody screening (ELISA). If positive, it is confirmed by testing for the viral protein. Early diagnosis is important as treatment can improve symptoms and reduce long-term damage. HIV patients well-managed on antiretroviral medications do very well and have the same life expectancy as normal individuals. However some antiretroviral medications themselves can cause neuropathy.
Lyme antibodies testing is done in cases of Lyme disease, which is a bacterial infection transmitted by a tick. It is common in the Northeastern United States. Early symptoms are fever, headaches, fatigue and a unique target-shape skin rash. If untreated, Lyme disease progresses to the joints, heart and nervous system including the peripheral nerves. Therefore, early diagnosis is required to target treatment appropriately. Lyme disease is commonly diagnosed clinically; however, in ambiguous cases Lyme antibodies is used to screen for Lyme disease.
Hepatitis C antibodies: Hepatitis C is a chronic infection of the liver acquired from exposure to other people’s blood or through sex. It is associated with neuropathy commonly associated with cryoglobulinemia, which is a condition where antibodies precipitate in the blood vessels at low temperatures blocking them and causing inflammation in blood vessels and the organs. The skin and kidney are commonly affected. Testing for Hepatitis C antibodies is the first step in diagnosing the condition. If the Hepatitis C antibody screening is positive then Hepatitis C infection is confirmed by testing for hepatitis C RNA. Other causes of Cryoglobulinemia are other autoimmune diseases, leukemia, multiple myeloma and others.
Tests for Blood and Bone Marrow Cancers and Pre-cancers
Electrophoresis from blood or urine: This detailed examination of proteins can identify cancerous or precancerous blood conditions associated with peripheral neuropathy. Examples include multiple myeloma, Waldenström’s macroglobulinemia and monoclonal gammopathy.
Serum free light chains: This examination of kappa and lambda blood proteins can identify cancers or precancerous blood conditions associated with peripheral neuropathy.
Other Tests Performed on an Individual Basis
Oral glucose tolerance test: This is the most rigorous test for diagnosing diabetes and prediabetes. It requires no eating or drinking after the evening meal and then having your blood drawn before eating or drinking the next morning (fasting glucose). Patients are then given a sugary liquid to drink that contains a precise amount of glucose and then their blood glucose is remeasured at specific times after, often at 2 hours later.
Genetic (DNA) sequencing: Genetic testing is used when the medical person suspects that the neuropathy seems to affect members of the patient’s family line. This suspicion is learned from discussion with the patient then followed up with testing. The aim is to identify the genetic changes responsible for the hereditary neuropathy thereby giving a specific diagnosis. An example is Charcot-Marie-Tooth disease which is one of the most commonly inherited neurological disorders affecting 1 in every 2,500 people in the United States. There is nerve degeneration due to a lack of special proteins necessary in their functioning. Symptoms include muscle weakness and wasting, lack of coordination during walking, pins and needles sensation or poor sensations, high foot arch, and hammer toe. Treatment is multidisciplinary but there is no cure.
Abdominal fat-pad biopsy: involves removing a tiny amount of fat from under the skin of the belly using a needle and local anesthesia. This can detect deposits of abnormal protein known as amyloid. If this protein builds up in nerves, it can cause neuropathy.
- Hoffman, EM, Staff, NP, Robb, JM, et al. Impairments and comorbidities of polyneuropathy revealed by population-based analyses. Neurology. 2015;84:1644-1651.
- Farhad, K, Traub, R, Ruzhansky, KM, et al. Causes of neuropathy in patients referred as "idiopathic neuropathy". Muscle Nerve. 2015.
- Gallagher, G, Rabquer, A, Kerber, K, et al. Value of thyroid and rheumatologic studies in the evaluation of peripheral neuropathy. Neurology: Clinical Practice. 2013;3:90-98.
- Bednarik, J, Vlckova-Moravcova, E, Bursova, S, et al. Etiology of small-fiber neuropathy. J Peripher Nerv Syst. 2009;14:177-183.
- Latov, N, Kumar, G, Vo, ML, et al. Elevated blood mercury levels in idiopathic axonal neuropathy. JAMA Neurol. 2015;72:474-475.
- Ørstavik, K, Norheim, I, and Jorum, E. Pain and small-fiber neuropathy in patients with hypothyroidism. Neurology. 2006;67:786-791.
- Smith, AG and Singleton, JR. The diagnostic yield of a standardized approach to idiopathic sensory-predominant neuropathy. Archives of Internal Medicine. 2004;164:1021-1025.
- Koike, H, Takahashi, M, Ohyama, K, et al. Clinicopathologic features of folate-deficiency neuropathy. Neurology. 2015;84:1026-1033.
- Zivkovic, SA, Delios, A, Lacomis, D, et al. Small fiber neuropathy associated with multiple myeloma and IgA monoclonal gammopathy. Ann Hematol. 2009;88:1043-1044.
- Chin, RL and Latov, N. Peripheral neuropathy and celiac disease. Curr Treat Options Neurol. 2005;7:43-48.
- Heij, L, Dahan, A, and Hoitsma, E. Sarcoidosis and pain caused by small-fiber neuropathy. Pain Res Treat. 2012;2012:256024.
- Coutinho, BM, Bordalo, E, and Nascimento, OJ. Autonomic evaluation of hepatitis C virus infected patients. Arq Neuropsiquiatr. 2013;71:537-539.
- Marcos R.G.de Freitas, Osvaldo J.M.Nascimento, Ernestina A.M.Quaglino, et al. Small-fiber polyneuropathy in leprosy without skin changes. Arquivos de Neuro-Psiquiatria. 2003;61:542-546.
- Huang, J, Han, C, Estacion, M, et al. Gain-of-function mutations in sodium channel NaV1.9 in painful neuropathy. Brain. 2014.
- Callaghan, BC, Kerber, KA, Lisabeth, LL, et al. Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy. JAMA Neurol. 2014;71:1143-1149.
- Singleton, JR, Smith, AG, and Bromberg, MB. Painful sensory polyneuropathy associated with impaired glucose tolerance. Muscle Nerve. 2001;24:1225-1228.
- Dyck, PJ, Clark, VM, Overland, CJ, et al. Impaired glycemia and diabetic polyneuropathy: the OC IG Survey. Diabetes Care. 2012;35:584-591.
- Oomatia, A, Fang, H, Petri, M, et al. Peripheral neuropathies in systemic lupus erythematosus: clinical features, disease associations, and immunologic characteristics evaluated over a twenty-five-year study period. Arthritis Rheumatol. 2014;66:1000-1009.
- Sene, D, Cacoub, P, Authier, FJ, et al. Sjögren syndrome-associated small fiber neuropathy: Characterization from a prospective series of 40 cases. Medicine (Baltimore ). 2013.
- Chin, RL, Sander, HW, Brannagan, TH, et al. Celiac neuropathy. Neurology. 2003;60:1581-1585.
- Brannagan, TH, III, Hays, AP, Chin, SS, et al. Small-fiber neuropathy/neuronopathy associated with celiac disease: Skin biopsy findings. Archives of Neurology. 2005;62:1574-1578.
- McKeon, A, Lennon, VA, Pittock, SJ, et al. The neurologic significance of celiac disease biomarkers. Neurology. 2014;83:1789-1796.
- Thawani, SP, Brannagan, TH, III, Lebwohl, B, et al. Risk of neuropathy among 28232 patients with biopsy-verified celiac disease. JAMA Neurol. 2015.
- Hughes, RA, Umapathi, T, Gray, IA, et al. A controlled investigation of the cause of chronic idiopathic axonal polyneuropathy. Brain. 2004;127:1723-1730.
- Zambelis, T, Karandreas, N, Tzavellas, E, et al. Large and small fiber neuropathy in chronic alcohol-dependent subjects. J Peripher Nerv Syst. 2005;10:375-381.
- Üçeyler, N, Kahn, AK, Kramer, D, et al. Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case-control study. BMC Neurol. 2013;13:47. doi: 10.1186/1471-2377-13-47.:47-13.