The first steps in the evaluation and later management of plexopathy would consist of gathering a medical history and conducting a physical examination by a healthcare clinician. Motor function defect patterns detected within either the upper or lower extremities help with diagnosis of the disorder.

X-rays of the cervical spine, chest, and shoulder are usually ordered if symptoms point to acute Brachial plexopathy. If the physical history reveals a history of diabetes, collagen vascular disease, or symptoms of infection, the physician may order a series of blood tests including a complete blood count (CBC) and a comprehensive metabolic panel (CMP).

Plexopathy symptoms often resemble spinal cord disorders. A neurosurgical consultation is usually undertaken to ensure proper diagnosis, management, and treatment. Patients with chronic symptoms will likely be advised to follow up with outpatient care from either their health care provider or specialist.

Patients with diabetes and proximal (hip, thigh) pain and weakness are often suspected of having diabetic amyotrophy. More definitive diagnosis is commonly made with electrodiagnostic studies including nerve conduction studies (NCS) and electromyogram (EMG). Diabetic amyotrophy is often a diagnosis of exclusion in diabetic patients with a lumbosacral plexopathy for whom no other cause of lumbosacral plexopathy can be determined.

Proper management of diabetes mellitus can prevent proximal diabetic neuropathy from ever occurring.

The incidence of proximal diabetic neuropathy incidence is thought to be correlated to blood glucose control in diabetics, and is likely reversible with better control.

Medication helps reduce the pain involved in proximal diabetic neuropathy. Most patients take oral medication that is prescribed by a doctor. Common types of medication used to treat diabetic amyotrophy include anticonvulsives (e.g. gabapentin, pregabalin) as well as opioid medications, although the latter category is not optimally indicated for neuropathic pain.

For diagnosis of NPSLE, it must be determined whether neuropsychiatric symptoms are indeed caused by SLE, whether they constitute a separate comorbid condition, or whether they are an adverse effect of disease treatment. In addition, onset of neuropsychiatric symptoms may happen prior to the diagnosis of lupus. Due to the lack of uniform diagnostic standards, statistics about NPSLE vary widely.

Tests which aid in diagnosis include MRI, electrophysiological studies, psychiatric evaluation, and autoantibody tests.

Alcoholic polyneuropathy is very similar to other axonal degenerative polyneuropathies and therefore can be difficult to diagnose. When alcoholics have sensorimotor polyneuropathy as well as a nutritional deficiency, a diagnosis of alcoholic polyneuropathy is often reached.

To confirm the diagnosis, a physician must rule out other causes of similar clinical syndromes. Other neuropathies can be differentiated on the basis of typical clinical or laboratory features. Differential diagnoses to alcoholic polyneuropathy include amyotrophic lateral sclerosis, beriberi, Charcot-Marie-Tooth disease, diabetic lumbosacral plexopathy, Guillain Barre Syndrome, diabetic neuropathy, mononeuritis multiplex and post-polio syndrome.

To clarify the diagnosis, medical workup most commonly involves laboratory tests, though, in some cases, imaging, nerve conduction studies, electromyography, and vibrometer testing may also be used.

A number of tests may be used to rule out other causes of peripheral neuropathy. One of the first presenting symptoms of diabetes mellitus may be peripheral neuropathy, and hemoglobin A1C can be used to estimate average blood glucose levels. Elevated blood creatinine levels may indicate renal insufficiency and may also be a cause of peripheral neuropathy. A heavy metal toxicity screen should also be used to exclude lead toxicity as a cause of neuropathy.

Alcoholism is normally associated with nutritional deficiencies, which may contribute to the development of alcoholic polyneuropathy. Thiamine, vitamin B-12, and folic acid are vitamins that play an essential role in the peripheral and central nervous system and should be among the first analyzed in laboratory tests. It has been difficult to assess thiamine status in individuals due to difficulties in developing a method to directly assay thiamine in the blood and urine. A liver function test may also be ordered, as alcoholic consumption may cause an increase in liver enzyme levels.

Management of neuropsychiatric lupus is similar to the management of neuropsychiatric disease in patients without lupus. Treatment depends on the underlying causes of a patient’s disease, and may include immunosuppressants, anticoagulants, and symptomatic therapy.

It is difficult to assess the prognosis of a patient because it is hard to convince chronic alcoholics to abstain from drinking alcohol completely. It has been shown that a good prognosis may be given for mild neuropathy if the alcoholic has abstained from drinking for 3–5 years. During the early stages of the disease the damage appears reversible when people take adequate amounts of vitamins, such as thiamine. If the polyneuropathy is mild, the individual normally experiences a significant improvement and symptoms may be completely eliminated within weeks to months after proper nutrition is established. When those people diagnosed with alcohol polyneuropathy experience a recovery, it is presumed to result from regeneration and collateral sprouting of the damaged axons.

As the disease progresses, the damage may become permanent. In severe cases of thiamine deficiency, a few of the positive symptoms (including neuropathic pain) may persist indefinitely. Even after the restoration of a balanced nutritional intake, those patients with severe or chronic polyneuropathy may experience lifelong residual symptoms. Alcoholic polyneuropathy is not life-threatening but may significantly affect one's quality of life. Effects of the disease range from mild discomfort to severe disability.

Some physicians make a diagnosis on the basis of the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so many people with SLE may not pass the full criteria.

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence (IF). The pattern of fluorescence suggests the type of antibody present in the people's serum. Direct immunofluorescence can detect deposits of immunoglobulins and complement proteins in the people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called lupus band test) is an evidence of systemic lupus erythematosus.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE. The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in people with SLE are anti-U1 RNP (which also appears in systemic sclerosis and mixed connective tissue disease), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.

Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and kidney function (disturbed if the kidney is involved), liver enzymes, and complete blood count.

The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cells are only found in 50–75% of SLE cases, and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.