Peripheral neuropathy diagnostic study of choice

Peripheral neuropathy Microchapters
Home
Patient Information
Overview
Classification
Pathophysiology
Causes
Differentiating peripheral neuropathy from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Peripheral neuropathy diagnostic study of choice On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Peripheral neuropathy diagnostic study of choice All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Peripheral neuropathy diagnostic study of choice
CDC on Peripheral neuropathy diagnostic study of choice
Peripheral neuropathy diagnostic study of choice in the news
Blogs on Peripheral neuropathy diagnostic study of choice
Directions to Hospitals Treating Psoriasis
Risk calculators and risk factors for Peripheral neuropathy diagnostic study of choice

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]; Anum Ijaz M.B.B.S., M.D.[3]

Overview

Diagnostic evaluation of peripheral neuropathy is guided by clinical presentation, with testing used to identify underlying etiologies, characterize nerve involvement, and exclude alternative diagnoses. Length-dependent peripheral neuropathy (LDPN) is primarily diagnosed on the basis of signs and symptoms, while laboratory studies serve as the first-line diagnostic studies to detect common, treatable causes such as diabetes mellitus, vitamin B12 deficiency, and monoclonal gammopathies. Electrodiagnostic studies may be used selectively to confirm neuropathy, distinguish axonal from demyelinating processes, and evaluate atypical features, though routine electromyography (EMG) testing is not required in patients with symmetric diabetic neuropathy. Additional modalities, including autonomic testing and skin biopsy, are reserved for specific clinical scenarios such as prominent autonomic symptoms or suspected small fiber neuropathy.

Diagnostic Study of Choice

The following algorithm outlines a stepwise approach to the diagnosis of peripheral neuropathy.

Evaluation for Peripheral Neuropathy HISTORY SYMPTOMS: • Sensory: numbness, paresthesias, pain in the distal extremities • Motor weakness in the distal extremities • Autonomic: postural lightheadedness, dry eyes, dry mouth, nausea and vomiting, diarrhea, constipation, early satiety, difficulty initiating urination and incomplete bladder emptying, erectile dysfunction • Gait instability Location of symptoms: • Length dependent: Appears in longest nerve axons (eg, toes) and moves proximally over time • Non–length dependent: Affects proximal and distal nerve axon or multiple individual nerves (eg, multifocal) Symmetry of symptoms: • Symmetric: sensory or motor impairment occurs in same location on both extremities (eg, feet) • Asymmetric: sensory or motor impairment occurs on 1 extremity or is multifocal Time course: • Symptom onset could be days to weeks or months to years Risk factors and genetic considerations: • Diabetes • Alcohol use disorder • Gastrointestinal conditions leading to poor vitamin absorption • Medication toxicity e.g. chemotherapy • Hereditary neuropathy (eg, Charcot-Marie-Tooth disease) PHYSICAL EXAMINATION Sensory loss: • Test distal extremities for impairment and move proximally until normal sensation is felt • Vibration, proprioception, light touch, pinprick, and temperature Foot or ankle deformities: • Examine feet for pes cavus (high arches) and/or hammer toes Impaired proprioception: • Observe for Romberg sign: unsteadiness with feet together, arms outstretched,and eyes closed Motor impairment: •Observe feet for muscle atrophy and test for toe flexion/extension weakness (may involve ankles and hands), reduced or absent ankle reflexes, and unsteady or wide-based gait

TYPICAL LENGTH-DEPENDENT PERIPHERAL NEUROPATHY Features include: • Sensory involvement more prominent than motor • Symmetric signs and symptoms • More severe in most distal extremities (eg, toes and feet) • Symptom onset and progression over months to years

ATYPICAL PERIPHERAL NEUROPATHY Features include: • Severe motor weakness or autonomic symptoms • Non–length dependent pattern of sensory loss or weakness • Asymmetric pattern of sensory and/or motor impairment • Systemic signs and symptoms (eg, weight loss, fever, rash) • Symptom onset and progression over days to weeks

Laboratory evaluations to determine etiology • Fasting blood glucose • Serum B12 with methylmalonic acid • Serum protein electrophoresis with immunofixation • Hemoglobin A1c with fasting glucose Common etiologies include: • Diabetes• Nutrition imbalance (eg, B12, copper, thiamine)• Alcohol use disorder• Medication toxicity• Monoclonal gammopathies• Hereditary

Refer to neuromuscular specialist • Laboratory testing for immune, inflammatory, infectious, or neoplastic etiologies. • Autonomic testing (eg, quantitative sudomotor axon reflex test, heart rate response to deep breathing, Valsalva maneuver, tilt table test) for those with prominent autonomic symptoms • Lumbar puncture, nerve imaging, and nerve biopsy may also be considered

Nerve conduction study (NCS) and electromyography (EMG) • Confirm presence of peripheral neuropathy • Exclude other etiologies (eg, lumbar radiculopathies, cervical myelopathy, compressive mononeuropathies) • Identify pathophysiology: 1.Axonal degeneration: suggested by reduced motor and sensory amplitudes on NCS and neurogenic motor unit potentials on EMG 2.Demyelination: suggested by slowed conduction velocities, prolonged distal latencies, and motor conduction block and temporal dispersion on NCS

Clinical Diagnosis

The diagnosis of length-dependent peripheral neuropathy (LDPN) is primarily clinical, based on characteristic symptoms and examination findings. Diagnostic testing is used to identify an underlying etiology or clarify atypical presentations

Laboratory Studies

Laboratory testing is the initial diagnostic study of choice to identify common, treatable causes of LDPN. Recommended baseline testing includes:

• Blood glucose
• Serum vitamin B12 with metabolic markers (methylmalonic acid with or without homocysteine)
• Serum protein electrophoresis with immunofixation

If no cause is identified and fasting glucose is normal, additional evaluation for impaired glucose metabolism (HbA1c or oral glucose tolerance test) may be considered, particularly in patients with painful neuropathy.

Click here for detailed Laboratory Studies.

Electrodiagnostic Studies

Nerve conduction studies (NCS) and electromyography (EMG) can confirm peripheral neuropathy, define fiber type involvement, and distinguish axonal versus demyelinating pathology.

Typical LDPN electrodiagnostic features include:

• Sensory fibers affected earlier and more severely than motor fibers
• Lower extremities affected before upper extremities
• Symmetric abnormalities in nerves of similar length

Electrodiagnostic testing is most useful in patients with atypical features, diagnostic uncertainty, or concern for alternative diagnoses. Routine EMG is not required in patients with diabetes and symmetric neuropathy, as stated by the American Diabetes Association ,, though testing may still alter diagnosis or management in a substantial proportion of patients. EMG/NCS are particularly valuable for identifying mimics such as compressive neuropathies or radiculopathies.

Autonomic Testing

Autonomic testing is reserved for patients with prominent autonomic symptoms. Modalities include:

• Quantitative sudomotor axon reflex testing (QSART) for small-fiber involvement

The quantitative sudomotor axon reflex test (QSART) assesses sudomotor function by measuring sweat production at four standardized sites (foot, distal leg, proximal leg, and forearm). The test uses iontophoresis to noninvasively deliver acetylcholine into the skin, activating postganglionic axon terminals and stimulating eccrine sweat glands; the resulting sweat volume is collected and quantified. QSART has a sensitivity of approximately 73% to 80% for detecting distal small fiber neuropathy.

• Cardiovagal testing to assess heart rate variability

Cardiovagal testing evaluates autonomic cardiac function by measuring the heart rate response to deep breathing. An age-adjusted reduction in this response is nearly as sensitive as nerve conduction studies for detecting polyneuropathy, although precise quantitative estimates are not available.

Autonomic neuropathy is most commonly associated with diabetes, amyloidosis, toxic etiologies ( e.g. vincristine), and rarely autoimmune ( Sjogren syndrome) or paraneoplastic conditions.

Skin Biopsy

Skin biopsy assessing epidermal nerve fiber density is useful for confirming distal small fiber neuropathy characterized by pain and temperature dysfunction.When skin biopsy is performed, punch specimens are typically obtained approximately 10 cm proximal to the lateral malleolus and, in some cases, from an additional site such as the distal thigh. Epidermal nerve fiber density values below the 5th percentile relative to age- and sex-matched reference standards are considered abnormal. Skin biopsy demonstrates a sensitivity of approximately 80% and a specificity of about 90% for the diagnosis of small fiber neuropathy, with clinical history and physical examination serving as the standard of diagnosis.,

While diagnostically sensitive and specific, skin biopsy has limited utility in determining etiology and is constrained by inter-laboratory variability in normative values.,