AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mononeuritis multiplex is a painful asymmetric asynchronous sensory and motor peripheral neuropathy involving isolated damage to at least 2 separate nerve areas. Multiple nerves in random areas of the body can be affected. As the condition worsens, it becomes less multifocal and more symmetric. Mononeuropathy multiplex syndromes can be distributed bilaterally, distally, and proximally throughout the body.

Mononeuritis multiplex actually is a group of disorders, not a true distinct disease entity. Typically, the condition is associated with (but not limited to) systemic disorders such as diabetes, vasculitis, amyloidosis, direct tumor involvement, polyarteritis nodosa, rheumatoid arthritis, systemic lupus erythematosus, and paraneoplastic syndromes. Mononeuritis multiplex also may be associated with Lyme disease, Wegener's granulomatosis, Sjögren syndrome, cryoglobulinemia, hypereosinophilia, temporal arteritis, scleroderma, sarcoidosis, leprosy, acute viral hepatitis A, and acquired immunodeficiency syndrome (AIDS).

Pathophysiology

Mononeuritis multiplex involves damage to at least 2 separate nerve areas. This condition can become progressively worse over time. The damage to the nerves involves destruction of the axon (ie, the part of the nerve cell that is analogous to the copper part of a wire), thus interfering with nerve conduction. Common causes of damage include a lack of oxygen from decreased blood flow or inflammation of blood vessels. Approximately 33% of cases originate from unidentifiable causes.

Frequency

United States

The actual incidence in the United States is not known due to the widely varied underlying pathologies that may lead to the disorder. The primary disease process often is so dominant that the symptoms of mononeuritis multiplex simply are attributed to the initial disease and remain undiagnosed.

International

Same as frequency in the United States (see above).

Mortality/Morbidity

If the cause is identified early and is successfully treated, full recovery is possible. The extent of disability varies, from no disability to partial or complete loss of function and movement.

Race

No specific relation to race is known.

Sex

Mononeuritis multiplex exhibits equal incidence in men and women.

Age

Age of onset depends on the patient's age at occurrence of the associated disease process; however, this condition does tend to occur in older patients with relatively mild or even unrecognized diabetes for unknown reasons.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

A detailed and complete medical history is vitally important in determining the possible underlying cause of the disorder. Pain often begins in the low back or hip and spreads to the thigh and knee on one side. The pain usually is characterized as deep and aching with superimposed lancinating jabs that are most severe at night. Individuals with diabetes typically present with acute onset of unilateral severe thigh pain that is followed rapidly by weakness and atrophy of the anterior thigh muscles and loss of the knee reflex. Other possible symptoms that may be reported by the patient include the following:

• Numbness
• Tingling
• Abnormal sensation
• Burning pain - Dysesthesia
• Difficulty moving a body part - Paralysis
• Lack of controlled movement of a body part

Physical

Loss of sensation and movement may be associated with dysfunction of specific nerves. Examination reveals preservation of reflexes and good strength except in regions more profoundly affected. Some common findings of mononeuritis multiplex may include the following (not listed in order of frequency):

• Sciatic nerve dysfunction
• Femoral nerve dysfunction
• Common peroneal nerve dysfunction
• Axillary nerve dysfunction
• Radial nerve dysfunction
• Median nerve dysfunction
• Ulnar nerve dysfunction
• Tardive ulnar palsy
• Peroneal nerve palsy
• Autonomic dysfunction - The part of the nervous system that controls involuntary bodily functions, such as the glands and the heart

Causes

Mononeuritis multiplex most commonly is associated with diabetes mellitus and multiple nerve compressions.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Lyme disease
Sjögren syndrome
Cryoglobulinemia
Temporal arteritis
Scleroderma
Sarcoidosis
Leprosy
Acute viral hepatitis A
AIDS
Hypereosinophilia
Cryoglobulinemia
Paraneoplastic peripheral neuropathy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Laboratory tests are ordered, as appropriate, to identify underlying potential causes of the condition. Selection of appropriate tests is guided by the patient's history, physical examination, and symptoms. Examples include the following:
• • If Lyme disease is suspected, draw a Borrelia burgdorferi antibody titer.
  • If the human immunovirus is suspected, perform HIV blood tests.
  • If hepatitis is suspected as a causative agent, perform a hepatitis screen.
  • If a systemic inflammatory process is suspected, perform an erythrocyte sedimentation rate (ESR).
• The practitioner must carefully choose screening tests to maximize the likelihood of discovering the causative agent. Choices of screening laboratory tests include, but are not limited to, the following:
• • Complete blood count with a differential
  • Hepatitis screen
  • Blood sugar levels
  • Erythrocyte sedimentation rate

Imaging Studies

• Imaging studies are not indicated for the diagnosis of mononeuritis multiplex.

Other Tests

• The suspected cause as suggested by the history, symptoms, and pattern of symptom development helps determine which tests to perform.
• Electrodiagnostic studies are used only in conjunction with an accurate and complete history and physical examination.
• • Sensory nerve conduction studies
    • The lesion or lesions are distal to both the motor and sensory cell bodies and result in either axonal disruption/degeneration or abnormal axonal conduction.
    • Sensory nerve conduction studies (NCS) show abnormalities of decreased amplitude in the presence of axonal disruption. Physical examination will direct the electromyographic examination.
    • Sensory NCS are beyond the reference range for amplitude and/or latency only if a large enough percentage of the sensory axons are damaged. A lesion that eliminates conduction in less than 10% of the sensory axons produces a loss of amplitude that may not be detectable.
    • H-reflex latencies may be prolonged or absent.
  • Motor nerve conduction studies
    • Abnormalities are similar to those seen in axonal polyneuropathies and entrapment neuropathies with the exception of the anatomic distribution. A reduction in the sensory and motor action potential amplitudes and minimal alterations in nerve conduction velocity will be seen. Velocity may be slightly reduced compared with the reference range, but it does not usually decrease below 70-80% of the lower limit of the reference range. Additionally, the loss of motor axons should generate a reduced number of motor unit action potentials (MUAP) firing at high rates (ie, reduced recruitment). Abnormal findings directly depend on the severity and aggressiveness of the underlying disease.
    • A decrement of motor amplitude may be seen if there is significant denervation.
  • Needle electrode examination
    • Results of needle electrode examination can vary, depending on the time course of the disorder.
    • Findings are typically neuropathic and may include abnormal spontaneous membrane activity (positive sharp waves and fibrillation potentials) and increases in MUAP duration, amplitude, and polyphasia.

Procedures

• The performance of any procedure, such as a nerve biopsy, is dictated by the history and physical examination. The purpose of any procedure is to determine the primary pathologic process.
• A nerve biopsy may be performed to help distinguish between demyelination (destruction of parts of the myelin sheath covering the nerve) and axonal degeneration (destruction of the axon portion of the nerve cell), to identify inflammatory nerve conditions (neuropathies), or to confirm specific diagnoses.

Histologic Findings

In some cases, a nerve biopsy may be appropriate to determine the underlying cause (eg, a combination of perivascular inflammation and axonal loss or demyelination and axonal loss with multinucleated inflammatory cells). A pattern of necrotizing vasculitis of epineural arteries may be observed in HIV-related mononeuritis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Rehabilitation Program

Physical Therapy

Physical therapy (PT) may be recommended for patients with mononeuritis multiplex, and the specific treatment generally depends on the site involved. PT can help to prevent contractures and maintain strength by instructing the patient in range of motion (ROM) and strengthening exercises as appropriate. The physical therapist can assist the patient with positioning issues and recommend braces or splints (static and functional) to increase his/her independence with mobility.

Patients with mononeuritis multiplex often exhibit problems with diminished sensation and require instruction to improve their safety awareness. In some cases, a transcutaneous electrical nerve stimulation (TENS) unit may be recommended for pain control in patients with this condition. The physical therapist can instruct the patient in the appropriate setup and use of the unit.

Occupational Therapy

Occupational therapy is directed toward maintaining functional independence in patients with mononeuritis multiplex. This training may include instructing the patient in the use of adaptive techniques for activities of daily living (ADL). Built-up handles on eating utensils and adaptive aids (eg, long shoehorns, reachers) may be used to help the patient perform ADL such as dressing and eating. A job-site analysis may need to be completed by the physical therapist and/or occupational therapist to ensure occupational safety. Therapy can incorporate job-specific training for those individuals who would benefit.

Speech Therapy

Speech therapy usually is not required for patients with mononeuritis multiplex.

Recreational Therapy

The primary focus of recreational therapy is to maintain the patient's activity level and self-esteem during recovery.

Medical Issues/Complications

The physician must try to elucidate the underlying cause and initiate appropriate treatment.

• Disorders such as vasculitis can be fatal if not treated.
• Use caution in treating the patients who are insensate, especially with the use of modalities (eg, ice, heat).
• Monitor and help control blood sugar levels in individuals with diabetes.
• Institute nutritional supplementation.
• Monitor bony prominences for pressure points.
• Safety is an important consideration, and appropriate safety measures must be provided. Safety measures may include installation of railings, removal of obstacles (eg, loose rugs that may slip on the floor), installation of low-level lighting, testing of water temperatures before bathing, and implementation of other measures, as appropriate.

Consultations

• Neurologist - If an underlying neurologic condition is suspected
• Rheumatologist - If an underlying rheumatologic condition is suspected
• Infectious disease specialist- If evidence of an infectious etiology is present

Other Treatment

Most treatments are directed toward management of the underlying condition. Treatments should be directed according to the established protocols for those specific disease conditions.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The reduction of inflammation around the epineurium is the primary goal of treatment. Additional treatments are aimed at treating the primary cause and/or associated symptomology.

Drug Category: Corticosteroids

Can be helpful if the condition is due to vasculitis. Failure to recognize and treat vasculitis can result in fatal consequences.

Drug Category: Immunosuppressives

If the overlying condition is inflammatory or autoimmune in nature, immunosuppressives may be of limited benefit to those patients intolerant of steroids.

Drug Category: Anticonvulsants

To treat associated symptom of dysesthesia and neuropathic pain.

Drug Category: Tricyclic antidepressants

Analgesic for chronic and neuropathic pain.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Inpatient care should be directed as appropriate for the treatment of the primary disease.

Further Outpatient Care

• The patient should follow up with the primary physician for underlying disorders (eg, diabetes).
• The patient should follow up with the primary physician or with the rehabilitation physician for pain medications and/or monitoring of laboratory tests.

In/Out Patient Meds

• Over-the-counter analgesics are used for pain control.
• Prescription pain medications: The author of this article searched recent literature for treatment of neuropathic pain; the search returned 925 possible references, none of which advocated the use of opioid medication for neuropathic pain, either short term or long term.
• Various other medications may be used to reduce dysesthetic pain, which typically is a stabbing burning pain.
• • Traditional medical models for treating chronic and neuropathic pain are based on the use of tricyclic antidepressants (eg, amitriptyline, nortriptyline, desipramine). When appropriate, anticonvulsant drugs have been used to treat lancinating pain. Gabapentin, phenytoin, and carbamazepine most often are used as the drugs of choice. Valproate is used occasionally.
  • Advances in understanding of the pathophysiology of acute and chronic pain states may lead to newer, more effective pharmacologic approaches to treatment. The clinician must integrate symptoms, signs, and clinical evaluation when considering the treatment of neuropathic pain.
  • More effective and safer antiepileptic drugs have continued to benefit patients with conditions of chronic pain. Neurotransmitters such as serotonin, glutamate, substance P, CGRP, and GABA are the targets of research and development of pharmacologic therapies for acute and chronic pain. In addition, sodium activity and calcium activity play important roles in the pathology and treatment of these chronic medical problems.
  • Medications that increase gastric motility (eg, Reglan) may be administered. Gastric motility also may be increased by eating small frequent meals and by sleeping with the head elevated.
• Medications for bladder dysfunction – include bethanechol and oxybutynin.

Complications

• Recurrent or unnoticed injury to any part of the body Deformity
• Deformity
• Atrophy
• Disturbances of organ functions that are autonomically controlled (eg, cardiac, gastric, bladder)
• Decreased self-esteem and decreased social interaction due to inability to participate in activities because of pain or incoordination
• Relationship problems associated with impotence

Prognosis

• Recovery typically is the course, and it may take months to years. The same syndrome has a tendency to recur after an interval of months or years.

Patient Education

• If the causative factor is discovered, education is directed toward avoidance of the initiating cause or pathogen. Additionally, recognition of early symptomology should be encouraged so that early treatment can be sought.
• Persons with one occurrence of mononeuritis multiplex are more prone to a recurrence.
• Persons with decreased sensation should be instructed to frequently check their feet or other affected areas for bruises, cuts, wounds, or other injuries. Also, patients who are insensate or incapacitated should be instructed to avoid prolonged pressure on various points on the body (eg, knees, elbows, sacrum) so as to avoid the development of pressure sores or ulcers.
• Safety awareness instruction is important to these patients because of their impaired sensation and decreased ability to compensate for limitations. The patient should be instructed to assure there is always adequate lighting, to test the water temperature before bathing or immersing body parts, and to wear protective shoes (no open toes or high heels).

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The main potential medicolegal pitfall stems from not obtaining a complete history and physical examination, thus allowing the main underlying disease process to go undetected/undiagnosed. As mentioned previously, not initiating early treatment for vasculitis could result in death. Legal consequences could arise should one not recognize an early viral infection or the symptomology of HIV, thus leading to delayed treatment.
• Additional medicolegal liability may arise from not fully informing patients of potential adverse side effects of medications.
• Both the physician and the patient should have the understanding that the nerve pain may be persistent for an extended period and may require ongoing treatment, with possible referral to a comprehensive pain treatment center. Both must have realistic expectations.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Adams RD, Victor M, Ropper AH. Multiple mononeuropathy and radiculopathy. In: Principles of Neurology. 6th ed. New York, NY: McGraw-Hill; 1996:. 1326.
• Bajwa ZH. A rational polypharmacy for a complex phenomenon (neuropathic pain). Presented at: 19th Annual Meeting of the American Pain Society;. November 2, 2000.
• Braddom RL. Mononeuritis multiplex. In: Physical Medicine and Rehabilitation. Philadelphia, Pa: WB Saunders; 1996:. 986-7.
• Delisa JA. Mononeuropathy multiplex syndromes and plexopathies. In: Delisa JA, Gans BM, eds. Rehabilitation Medicine. Philadelphia, Pa: JB Lippencott; 1993:. 297-8.
• Dumitru D. Textbook of Electrodiagnostic Medicine. Philadelphia, Pa: Mosby;1995.
• Farrar J, Hirsch J, Nicholson B. Novel approaches to the understanding and treatment of neuropathic pain. Program and Abstracts of the 19th. Annual Scientific Meeting of the American Pain; Symposium Abstract 112; November;Atlanta, Ga.
• Galer B, Backonja M. Zonisamide for neuropathic pain: dose ranging pilot study. Program and Abstracts of the 19th. Annual Scientific Meeting of the American Pain; November 2-5, 2000;Atlanta, Ga.
• Greenberg MS. Handbook of Neurosurgery. 4th ed. NY: Thieme Medical Publishers: 1990.
• Kimura J. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice. 2nd ed. Philadelphia, Pa: FA Davis;1989.
• Krendel DA, Costigan DA, Hopkins LC. Successful treatment of neuropathies in patients with diabetes mellitus. Arch Neurol. Nov 1995;52(11):1053-61. [Medline].
• Mahadevan A, Gayathri N, Taly AB, et al. Vasculitic neuropathy in HIV infection: a clinicopathological study. Neurol India. Sep 2001;49(3):277-83. [Medline].
• National Organization for Rare Disorders, Inc. National Organization for Rare Disorders Report on Peripheral Neuropathy. British Columbia Health Guide. 2005;[Full Text].
• Olney RK. AAEM minimonograph #38: neuropathies in connective tissue disease. Muscle Nerve. May 1992;15(5):531-42. [Medline].
• Panicker JN, Nagaraja D, Ratnavalli E, Pal PK. A rare cause for mononeuritis multiplex. Neurol India. Mar 2004;52(1):131-2.
• Parker JN, Parker PM. The Official Patient's Sourcebook on Peripheral Neuropathy: A Revised and Updated Directory for the Internet Age. 2002;156, 244. [Full Text].
• Parry GJ. Mononeuropathy multiplex (AAEE case report #11). Muscle Nerve. Jul-Aug 1985;8(6):493-8.
• Portenoy RK. COSA #102-99: A Pilot Dose-Range Finding Study of Zonegran (Zonisamide) in Patients with Neuropathic Pain Conditions - Protocol ZNS-503. Available at: http://www.stoppain.org/education_research/clinical.html. [Full Text].
• RxList. Zonegran-Zonisamide. Available at: http://www.rxlist.com/cgi/generic3/zonisamide_ad.htm. [Full Text].
• Wiederholt WC. Neurology for Non-neurologists. 4th ed. Philadelphia, Pa: WB Saunders; 2000:. 194.

Article Last Updated: Aug 9, 2006