Mononeuritis Multiplex

Updated: Jan 06, 2021
  • Author: Divakara Kedlaya, MBBS; Chief Editor: Dean H Hommer, MD  more...
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Practice Essentials

Mononeuritis multiplex is a painful, asymmetrical, 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 symmetrical. Mononeuropathy multiplex syndromes can be distributed bilaterally, distally, and proximally throughout the body. (See Presentation.) [1, 2, 3]

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 the following (see Causes, Presentation, Workup, and Treatment):

Signs and symptoms of mononeuritis multiplex

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. 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

Workup in mononeuritis multiplex

Laboratory tests ordered in the workup of mononeuritis multiplex include the following:

  • Complete blood count (CBC) with a differential

  • Fasting blood glucose levels

  • Borrelia burgdorferi antibody titer - If Lyme disease is suspected

  • Human immunodeficiency virus (HIV) blood tests - If HIV infection is suspected

  • Hepatitis screen - If hepatitis is suspected as a causative agent

  • Erythrocyte sedimentation rate (ESR) and C-reactive protein level - If a systemic inflammatory process is suspected

  • Autoimmune profile

  • Herpesviridae serology

  • Parvovirus B-19 antibodies

In some cases, a nerve biopsy may be appropriate to determine the underlying cause of mononeuritis multiplex (eg, a combination of perivascular mononuclear inflammatory cells and multifocal axonal loss and axonal loss with multinucleated inflammatory cells). [4]

Electrodiagnostic studies are used only in conjunction with an accurate and complete history and physical examination. The lesion or lesions are distal to the motor and sensory cell bodies and result in either axonal disruption/degeneration or abnormal axonal conduction.

Management of mononeuritis multiplex

Physical therapy (PT) may be recommended for patients with mononeuritis multiplex, with the specific treatment generally depending on the site involved. PT can help to prevent contractures and maintain strength through the use of range of motion (ROM) and strengthening exercises, as appropriate.

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 (ADLs).


Pathophysiology and Etiology

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) and therefore interferes with nerve conduction. Common causes of damage include a lack of oxygen from decreased blood flow or inflammation of blood vessels causing destruction of the vessel wall and occlusion of the vessel lumen of small epineurial arteries.

Mononeuritis multiplex can be associated with many different conditions, as described below.

Mononeuritis multiplex can be associated with the following infections:

  • Lyme disease [18]

  • Leprosy [19, 20, 21]  - An Indian study, by Jaiswal et al, found mononeuritis multiplex to be the most common clinical presentation in a cohort of 18 patients with Hansen neuritis, with nerve conduction studies revealing the condition’s presence in 13 (72.2%) cases; severe sensory axonopathy was more prevalent than severe motor axonopathy [22]

  • Acute viral hepatitis A [23]

  • Hepatitis B [24]

  • Hepatitis C [25, 26]

  • Acute parvovirus B-19 infection [27]

  • Herpes simplex virus infection [28]

  • AIDS and HIV infection [29, 30]

Mononeuritis multiplex can be associated with the following rheumatologic disorders:

  • Wegener granulomatosis [31, 32]

  • Henoch-Schönlein syndrome [6, 33]

  • Sjögren syndrome [34, 35]  - A study from Singapore, by Kam et al, of 102 patients with primary Sjögren syndrome found that among individuals with peripheral nervous system manifestations, the most common were sensory neuropathy (77.8%), motor neuropathy (11.1%), and mononeuritis multiplex (11.1%) [36]

  • Behçet’s disease [37, 38]

  • Temporal (giant cell) arteritis [39]

  • Systemic lupus erythematosus [14, 15]

  • Rheumatoid arthritis [12, 13]

  • Polyarteritis nodosa - A retrospective study by Criado et al of 22 cases of cutaneous polyarteritis nodosa found that a quarter of the patients had mononeuritis multiplex [11, 40]

  • Scleroderma [41]

Mononeuritis multiplex can be associated with the following chronic conditions:

  • Diabetes mellitus [1, 3]

  • Amyloidosis [8]

  • Neurosarcoidosis [42, 43]

  • Celiac disease [44]

Mononeuritis multiplex can be associated with the following cancer-related conditions:

  • Chronic graft versus host disease (GVHD) [45]

  • Direct tumor invasion with intraneural spread - Lymphoma, [10] B-cell leukemia, [9] carcinoid tumor [46]

  • Paraneoplastic - Small cell lung cancer [16, 17]

Mononeuritis multiplex can be associated with the following hematologic conditions:

  • Churg-Strauss syndrome [47, 48]

  • Hypereosinophilia

  • Cryoglobulinemia [49]  - A single-center, retrospective study by Feldman et al found that of 131 patients with possible or definite cryoglobulinemia-associated neurologic symptoms, 16 (12.2%) had mononeuritis multiplex [50]

  • Hypereosinophilia [51]

  • Atopy-related peripheral neuritis (see below) [52]

  • Idiopathic thrombocytopenic purpura [53, 54]

Mononeuritis multiplex can be associated with the following miscellaneous conditions:

  • Amphetamine angiitis [55]

  • Gasoline sniffing [56]

In addition, mononeuritis multiplex can be associated with the genetic disorder Tangier disease [57, 58] and with multiple compression neuropathies.

Moreover, in a study of 157 patients with eosinophilic granulomatosis with polyangiitis, Cottin et al found mononeuritis multiplex to be associated with cases that included systemic vasculitis and the presence of antineutrophil cytoplasmic antibodies. [59]

Persons with one occurrence of mononeuritis multiplex are more prone to a recurrence. Mononeuritis multiplex can become progressively worse over time. Approximately 33% of cases originate from unidentifiable causes. [60]

In a cross-sectional, Japan-wide survey, Isobe et al found that patients with atopy-related peripheral neuritis (n = 133) tended to develop mononeuritis multiplex, with their lower limbs predominantly affected. The investigators also determined that most patients with atopy-related peripheral neuritis were female and that individuals with the disease tended to have a higher eosinophil count than did patients in the study with atopic myelitis. [52]

A study by Needham et al found mononeuritis multiplex in 11 out of 69 patients (16%) with severe coronavirus disease 2019 (COVID-19) who were discharged from a hospital intensive care unit (ICU). Indications were that the condition developed during prolonged mechanical ventilation. The investigators state that although mononeuropathies are a known complication of anesthesia and intensive care, the patients in their study stood apart with regard to the percentage of persons affected, the number of nerves involved per patient (slightly more than three on average), and the specific nerves, such as the proximal sciatic, that were impacted. [61]



The actual incidence of mononeuritis multiplex in the United States and rest of the world is not known due to the widely varied etiologies that may lead to this 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.

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



If the cause of mononeuritis multiplex is identified early and is successfully treated, full recovery is possible, although it may take months to years. The same syndrome has a tendency to recur after an interval of months or years.

The extent of disability varies, ranging from no disability to partial or complete loss of function and movement. Complications in mononeuritis multiplex include the following:

  • Recurrent or unnoticed injury to any part of the body

  • Deformity

  • Atrophy

  • Disturbances of organ functions that are autonomically controlled (eg, cardiac, gastric, bladder)

  • Decreased self-esteem and decreased social interaction due to an inability to participate in activities because of pain or incoordination

  • Relationship problems associated with impotence

A Danish study by Al-Zuhairy et al found that compared with healthy controls, patients who had suffered from multifocal motor neuropathy, a form of mononeuritis multiplex, for a median period of 24 years had a 9% decrease in the Rasch-built Overall Disability Scale for Multifocal Motor Neuropathy, a three-fold increase in the Neuropathy Impairment Score, a 29% reduction in isokinetic strength, a 56% decrease in grip strength, a 13% prolongation of the Timed 25-Foot Walk, and a 20% impairment measured via the EQ-5D-DL index value. [62]


Patient Education

If the causative factor for a patient's mononeuritis multiplex 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 decreased sensation should be instructed to frequently check their feet or other affected areas for bruises, cuts, wounds, or other injuries. In addition, 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 discourage the development of pressure sores or ulcers.

Safety awareness instruction is important for these patients because of their impaired sensation and decreased ability to compensate for limitations. The patient should be instructed to ensure that 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).